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Study ID: LP0190-1488 CP Project ID: LEO20488

Version No: 3.0 Version Date: 23-Mar-2022

eCRF Completion Guidelines

QMS Document Name: eCRF Completion Guidelines of 70

QMS No (include version ref): DMF-486-GL.00 Document date 29MAR2019

CONFIDENTIAL

CLINICAL STUDY PROTOCOL

LP0190-1488

PROCESSED IN EDC SYSTEM

VERSION: 3.0 AUTHOR: Ilona Boehm

EFFECTIVE DATE: 23-MAR-2022






CONFIDENTIAL

Document History

Version Date Description of the change Changed by

1.0 16-June-2021 Final Version Christine Zimmermann

1.1 07-October-2021 Adaption of section “System access” and Trouble Shooting” to reflect change of mail domain for iMedidata

Christine Zimmermann

1.2 29-October-2021

Updates due to protocol amendment 1 that lead to eCRF changes; updates due to LEO DM comments received on 13-OCT-2021; updates due to internal review at Clinipace for next client review

Christine Zimmermann / Ilona Boehm /Ana-Maria Deac

1.3 02-November-2021 Updates due to client review Ilona Boehm

2.0 03-November-2021 Final Version Ilona Boehm

2.1 01-March-2022

Updates to “Prior and Concomitant medication”: new instructions for Study indication “Atopic dermatitis” added.

Ilona Boehm

2.2 10-March-2022

Updates to Central lab 2 for Visit 2 (Screening/run-in) Updates to IMP dispense and return for half-dose

Ilona Boehm

2.3 14-March-2022 Updates to Subject Eligibility (per sponsor request by mail from LEO DM sent on 14-Mar-2022)

Ilona Boehm

2.4 22-March-2022

Updates to Subject Eligibility provided by LEO DM. Corrections done by CP DM to this new text (Record “No” if subject did not meet all inclusion criteria that can be fully evaluated at screening or if subject met any eligibility criteria for the study.)

Ilona Boehm

3.0 23-March-2022 Final version Ilona Boehm






CONFIDENTIAL

Table of Contents

DOCUMENT HISTORY ................................................................................................................... 2

TABLE OF CONTENTS .................................................................................................................. 3

INTRODUCTION .............................................................................................................................. 5

SYSTEM ACCESS .......................................................................................................................... 5

TROUBLE SHOOTING AND SUPPORT ........................................................................................ 6

GENERAL INSTRUCTIONS............................................................................................................ 7

PRANCER RTSM DATA TRANSFER (4G INTERACTIVE RANDOMIZATION TOOL (IRT) SYSTEM) .............. 7 SUBJECT IDENTIFICATION ............................................................................................................... 8 ENTRIES ........................................................................................................................................ 8

SCREEN FAILURES ....................................................................................................................... 9

EARLY TERMINATION (ET) OF SUBJECTS ............................................................................... 10

UNSCHEDULED VISIT .................................................................................................................. 11

SOURCE DATA ............................................................................................................................. 11

CRF STRUCTURE ......................................................................................................................... 12

INACTIVATING AND REACTIVATING PAGES ........................................................................... 13

LOG LINES .................................................................................................................................... 13

INACTIVATING AND REACTIVATING LOG LINES ................................................................................. 13 NUMERIC FIELDS .......................................................................................................................... 13 DATE FIELDS ................................................................................................................................ 14 TIME FIELDS ................................................................................................................................. 15 RADIO BUTTONS .......................................................................................................................... 15 CHECK BOXES ............................................................................................................................. 16 ENTERING COMMENTS .................................................................................................................. 16 MISSING DATA .............................................................................................................................. 16 DROP DOWN LIST BOXES............................................................................................................... 16 DERIVED FIELDS ........................................................................................................................... 16 WORKFLOW AND QUERIES ............................................................................................................ 17 VERIFICATION .............................................................................................................................. 17 DATA FREEZE ............................................................................................................................... 18 DATA LOCK .................................................................................................................................. 18 INVESTIGATOR SIGNATURE – APPROVAL PROCESS ........................................................................ 18

INSTRUCTIONS FOR THE STUDY-SPECIFIC ECRF MODULES .............................................. 19

VISIT ........................................................................................................................................... 19 SUBJECT IDENTIFICATION .............................................................................................................. 19 INFORMED CONSENTS ................................................................................................................... 20 RESCREEN .................................................................................................................................. 20 DEMOGRAPHICS ........................................................................................................................... 21 WASHOUT .................................................................................................................................... 23 SUBJECT ELIGIBILITY .................................................................................................................... 24 ATOPY HISTORY ........................................................................................................................... 26 MEDICAL AND SURGICAL HISTORY ................................................................................................. 29 MEDICAL AND SURGICAL HISTORY - CONTINUED ............................................................................. 30 ECZEMA AREA AND SEVERITY INDEX (EASI) ................................................................................... 31






CONFIDENTIAL

ECZEMA AREA AND SEVERITY INDEX (EASI) - CONTINUED ............................................................... 32 VALIDATED INVESTIGATOR GLOBAL ASSESSMENT (VIGA-AD) ......................................................... 33 SCORING ATOPIC DERMATITIS (SCORAD) .................................................................................... 34 SCORING ATOPIC DERMATITIS (SCORAD) - CONTINUED ................................................................ 35 PHYSICAL EXAMINATION ............................................................................................................... 36 PHYSICAL EXAMINATION 2 ............................................................................................................ 36 VITAL SIGNS ................................................................................................................................ 37 ECG ........................................................................................................................................... 38 ECG 2 ........................................................................................................................................ 38 CENTRAL LABORATORY ................................................................................................................ 39 CENTRAL LABORATORY 2 .............................................................................................................. 40 ACTIGRAPHY ................................................................................................................................ 41 ACTIGRAPHY 2 ............................................................................................................................. 41 BODY MEASUREMENTS ................................................................................................................. 42 FASTING ...................................................................................................................................... 42 URINE PREGNANCY TEST .............................................................................................................. 42 ADDITIONAL PK DUE TO QTCF PROLONGATION.............................................................................. 43 PHARMACOKINETICS..................................................................................................................... 43 BLOOD BIOMARKERS .................................................................................................................... 43 SKIN BIOPSY – LESIONAL, NON-LESIONAL ....................................................................................... 44 SKIN BIOPSY – LESIONAL .............................................................................................................. 44 RANDOMISATION .......................................................................................................................... 45 IMP ADMINISTRATION AND COMPLIANCE ........................................................................................ 46 IMP DISPENSE AND RETURN ......................................................................................................... 47 EARLY TERMINATION .................................................................................................................... 48 AE/CM/CP EVENTS ..................................................................................................................... 48 ADVERSE EVENT .......................................................................................................................... 49 ADVERSE EVENT -CONTINUED ....................................................................................................... 50 ADVERSE EVENT -CONTINUED ....................................................................................................... 51 ADVERSE EVENT -CONTINUED ....................................................................................................... 52 ADVERSE EVENT -CONTINUED (AESI) ........................................................................................... 53 ADVERSE EVENT -CONTINUED (AESI) ........................................................................................... 54 ADVERSE EVENT -CONTINUED (AESI) ........................................................................................... 55 ADVERSE EVENT -CONTINUED (AESI) ........................................................................................... 56 PRIOR AND CONCOMITANT MEDICATION ......................................................................................... 57 PRIOR AND CONCOMITANT MEDICATION - CONTINUED ..................................................................... 58 PRIOR AND CONCOMITANT MEDICATION - CONTINUED ..................................................................... 59 PRIOR AND CONCOMITANT MEDICATION - CONTINUED ..................................................................... 60 PRIOR AND CONCOMITANT MEDICATION - CONTINUED ..................................................................... 61 CONCURRENT PROCEDURES ......................................................................................................... 62 UNSCHEDULED VISIT .................................................................................................................... 63 UNSCHEDULED - TYPE OF ASSESSMENT ......................................................................................... 64 END OF TREATMENT - TREATMENT COMPLETION/DISCONTINUATION ................................................ 65 END OF TRIAL - TRIAL COMPLETION/DISCONTINUATION ................................................................... 66 END OF TRIAL - TRIAL COMPLETION/DISCONTINUATION - CONTINUED ............................................... 67 END OF TRIAL - TRIAL COMPLETION/DISCONTINUATION - CONTINUED ............................................... 68 SCREEN FAILURE.......................................................................................................................... 69 COMMENTS LOG ........................................................................................................................... 70






CONFIDENTIAL

Introduction This document contains instructions on how to complete the electronic Case Report Forms (eCRF) in Medidata Rave for this study. It is important for data analysis purposes that subject data is collected in a uniform manner by the numerous institutions participating in this study. Therefore, the eCRF Completion Guideline is an important reference to use when completing the eCRF. All persons involved in the data collection/data cleaning of this study must familiarize themselves with this guideline. Adherence to this guideline will minimize the number of requests for data clarifications. These guidelines are available from a link in Rave from the home page as well as from the individual forms.

System Access

New users will receive an account activation e-mail from Medidata [email protected]. (including a link to create a user profile (username and password). (From October 2021 on, the e-mail address changed from [email protected] to [email protected]). Users who already have a Medidata account will see invitations in the Tasks pane on their iMedidata home page. NOTE: The account activation e-mail is only valid for 30 days. If the user does not use the link within 30 days, a new account activation e-mail will need to be sent. In this case, the site should contact the CRA. All users will be required to complete an on-line training. Upon completion of the training course, users will automatically have access to the eCRF of the study. Once a user has taken and passed a required course, they do not have to retake it to access other teams or studies that require it. However, if a change is made either to the application or to update the course, users may have to retake a course. Each site will have access to its own data only. Username and password should not be shared with others. For security reasons, please do not leave password information in a place where others may have access to it. Passwords are valid for 120 days and require to be at least eight (8) characters in length, contain at least one uppercase letter, one lowercase letter, and one number, to be at least of moderate strength, and not to be one of the last ten (10) passwords. Upon password expiration, users will automatically be prompted to change their password at login. For password re-sets, please see following section “Trouble Shooting and Support”. NOTE: Data may be entered into Rave by two roles: Clinical Research Coordinator (sometimes also referred to as Site Coordinator or Study Nurse) and Investigator. Users with one of these roles may also respond to queries.






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Trouble Shooting and Support For technical assistance, site staff should contact the Medidata Helpdesk via email to [email protected]. (From October 2021 on, this e-mail address changed from [email protected] to [email protected]).

What’s the Potential Impact If your associated systems that accept Medidata emails are not enabled to whitelist the @3ds.com email domain, those emails could be rejected or go into a SPAM container. Communications could be disrupted. For non-technical issues regarding completion of the eCRFs sites should contact their Monitor primarily. The CRA may reach out to Clinipace Data Management if further support is needed Lead CDM: [email protected], CDM backup: [email protected], CDM backup 2: [email protected]) or to LEO Pharma Data Management.

On the top right-hand corner of each RAVE screen, there is a HELP icon that could be clicked for general RAVE instructions. The maximum number of incorrect logins before accounts get locked is 5. When this happens, the account needs to be restored by clicking on the “Forgot Password?” link on the login page. You will have to enter the e-mail address linked to the account. An e-mail will be sent to this address with a link to create a new password. NOTE: Rave is not validated to work in iOS (Apple) or Android phone platform internet browsers.






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General Instructions Completion and signature of the eCRFs for all subjects at the site may be the responsibility of one or more study staff member(s) listed on the Site Delegation and Signature Log. The Investigator is the only staff member that can apply an electronic signature. The eCRFs need to be signed electronically by the Investigator to confirm that all data are completely and accurately entered. The eCRF is set up ‘dynamically’, which means that depending on an entry made by the site, sections will get enterable and/or pages/visits will be added for the subject to reflect the appropriate needs. This feature is reversible, and pages/visits will disappear, or sections will get non-enterable (greyed out) once the triggering entry is changed. NOTE: It is extremely important to FIRST enter the respective visit date Information at each visit, as well as all Adverse Events and Prior and concomitant medication, to display for all eCRF dynamics/defaults correctly (i.e., all adverse events or prior and concomitant medication need to be entered to ensure they are available for dynamic linking on other eCRF pages).

Prancer RTSM data transfer (4G Interactive Randomization Tool (IRT) system) The Prancer Randomization and Trial Management (RTSM) system is where the subject is first created. NOTE: The access to RAVE does not grant access to Prancer RTSM, a separate training would be needed for the access. Data on the fields below are automatically loaded into RAVE from Prancer RTSM. These fields cannot be modified in the RAVE EDC system. They are read only and protected and can be identified by the suffix “(Transferred from IRT)”. Any changes need to be made inside the Prancer RTSM system.






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Subject Identification Once a subject has been added in the Prancer RTSM system, the subject number and site ID is then transferred into Medidata RAVE. The format for Subject numbers is ssss-yyyy-zz, where:

ssss = trial number = e.g. 1488

yyyy = LEO unique site location ID (without country identifier)

zz = serial participant number starting from 01 for the first participant at a site

Example: 1488-1001-01. The following folders will then appear for data entry: Visit 1 (Screening) Visit 2 (Screening/run-in) AE/CM/CP events Trial completion/discontinuation Screen Failure Comments Log The following information will be transferred from 4G IRT system:

• Subject and site identification number

• Screening: date of birth, sex, age at screening

• Re-screen: previous subject identification number

• Randomisation: date of randomisation

• Screen failure: Date of screen failure

• IMP dispense and return: Kit number(s)

Entries NOTE: Data should be entered into the eCRF in a timely manner and within 5 business days of the subject visit.

All entries must be complete and entered in English. Avoid using abbreviations and symbols wherever possible. Do not use special characters (e.g. letters with accents, cedilla, semicolon, dollar sign), since special characters cause problems during data evaluation. In general, ensure that there are no missing data (blank fields) in the eCRF. If additional specification is requested for an item in the eCRF, please ensure that a specific entry is made (e.g. “Was the ECG performed?”, if “Yes” is ticked, enter all information). There may be some CRF pages where not all information is available at once, e.g. on the Central Laboratory form the site may tick that blood sampling was performed, but the result is not yet available. If the result is not entered within the next 4 days a query will fire. Other queries may fire with a delay of 1 day awaiting user’s data entry on a 2nd CRF page.






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Ensure that all data in the eCRF reflect the source data. If data entered is non-conformant (e.g. letters entered into a numeric field or an impossible date),

then the field is flagged as non-conformant and must be corrected. If the data is not corrected, Data Management will issue a query for this field. NOTE: Visit folders appear dynamically in subjects’ eCRF. See section ‘Subject Identification’ for folders that appear right from the beginning. Other visit folders are triggered by data entry, e.g., usually the next visit becomes visible once the visit date of the current visit is entered/saved.

Screen Failures Screening failures are all subjects who provided informed consent but are not randomized to treatment. In addition, subjects who withdraw/are withdrawn from the trial prior to randomization will be considered screening failures. An appropriate reason should be provided on the Screen failure form (see Visit Screen failure). The following pages must be completed:

• Visit 1 (Screening) with:

• Visit date

• Informed Consents

• Demographics

• Subject Eligibility

• ECG (only, if performed and transferred to the ECG vendor)

• Central Safety Lab (only, if a sample has been taken and send to the central laboratory)

• Visit 2 (Screening-run-in), if applicable

• Visit 3/Week 0, if applicable NOTE: There is no need to fill in details of further assessments, irrespective of whether performed or not). For consistency reasons and reconciliation of data, ECG form or Lab assessment form should be completed if an ECG or a lab sample was processed by the ECG/Lab vendor before the subject was determined to be a screen failure.

• Visit AE/CM/CP events o Answer the question 'Did the subject have any adverse events since screening'. If the

question is answered ‘Yes’, respective details must be entered on an Adverse Event form. No information about Concomitant Medication or Concurrent Procedures needs to be provided.

• Visit Screen failure o Screen failure form including reason for screen failure

Detailed instructions on the completion of each form can be found in the section ‘Instructions for study-specific eCRF modules.






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Early Termination (ET) of subjects For a subject discontinuing from study after randomization but before week 16 the following eCRF pages must be completed:

NOTE: A subject stopping IMP prematurely is encouraged to stay in the trial without getting more IMP. The "end of trial" form is only to be filled in when the entire trial is stopped, which may be after the IMP is stopped.

• For all subjects (either No IMP or IMP was administered):

• Visit Trial completion/discontinuation including End of Trial form

• AE/CM/CP events o If one of the questions is answered ‘Yes’, respective forms must be completed.

• If IMP was administered, in addition:

• End of treatment/Visit 16

• Safety follow-up visit (7 days after the last IMP application), if performed

• Early IMP termination including EASI, VIGA_AD, SCORAD, Physical examination 2, Vital Signs, Fasting, ECG 2, Urine pregnancy test, Central Laboratory 2, Pharmacokinetics, Blood biomarkers, Skin Biopsy – lesional, Actigraphy 2, Early termination, if performed

• Treatment completion/discontinuation including End of treatment form

Detailed instructions on the completion of the forms can be found in the section ‘Instructions for study-specific eCRF modules’.






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Unscheduled Visit On the subject casebook homepage please click on the ‘Add event’ drop-down box and select the Unscheduled Visit to be added for entry and save.

This will trigger the Unscheduled visit – type of assessment page.

The reason for the Unscheduled visit should be selected. If Adverse event/safety is selected, please record the Adverse event as appropriate. The "Unscheduled Visit" is a folder where all additional examinations should be recorded, regardless of when they were done. This visit in the eCRF is not a complete/normal visit, i.e. not all eCRF pages need to be entered (e.g. if only additional vital signs were measured, please only enter an additional vital signs eCRF page). NOTE: Detailed instructions on the completion of the Unscheduled Visit forms can be found in the section ‘Instructions for study-specific eCRF modules’.

Source Data All data entered in the eCRF should correspond accurately with the source documents. Otherwise, unnecessary queries will be generated.






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CRF structure Upon creation of a subject ID, the default matrix (set of folders and forms) is displayed. By clicking on a folder (e.g. Screening) all forms for this visit will be displayed. NOTE: Always start completing the eCRF by adding the Visit Date of the associated page/form.

Not all folders (visits) and forms will be available immediately upon creation of a new subject ID, they will become available upon entering the prerequisite data. When multiple instances of the same form/page are needed (e.g. concomitant medication or adverse event), a log form is used to add additional records to one form. Log forms can be in portrait or landscape mode.






CONFIDENTIAL

Inactivating and reactivating pages A page can be inactivated to indicate that no data is applicable to be entered on it (e.g. if data has been entered in error in a dynamically created form and the whole page needs to be disregarded). In case examinations/assessments of a conducted visit were not performed, the respective pages should be handled as follows:

• if the eCRF page has a leading “Yes” or “No” question for the examination/assessment, answer “No” to the question and specify a reason, if applicable

• if there is no leading “Yes” or “No” question, inactivate the eCRF page

Pages inactivated in error can be reactivated again. The permission to inactivate/reactivate pages is restricted to the CRA and Data Manager role.

Log lines Where several log lines are used in forms (e.g. Adverse Event or Prior and concomitant medication), the first row is ready for entry. You do not need to add the first log line from the “Portrait View”. If data is missing on the first row a query may appear to request completion. The “Add a new Log line” link should then be used for generating additional rows, as needed. To edit data within a log line, click any item in the log line or click the pencil at the right-hand side of the log line. Each additional log line must be saved separately. If a new log line is entered before the previous log line is saved, the previous entry gets lost.

Inactivating and reactivating log lines If a log line has been created in error (e.g. duplicated entry, blank line created in error) the log line can be inactivated by site personnel. NOTE: Please do not just leave the fields blank if an entire log line needs to be removed from the eCRF. This will create a blank record in the eCRF and queries may be raised asking for the missing data. Log lines inactivated in error can be reactivated again. The data entered previously can be activated again.

Numeric fields Numeric fields are left-aligned, and values can be entered with or without a leading ‘0’. If a value is less than 1 (e.g. 0.225) please always enter the leading 0 and use “.” as the decimal delimiter.






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Date fields The visit date should be completed according to the protocol schedule. Due to the in-built dynamics in this study, it is recommended that the visit date should always be entered at first before continuing with other data. Dates are entered in three fields in Rave: day of month (e.g. 01), month (from a drop-down list e.g. "Jan"), then year in four digits (e.g. 2014). Partial date: Partial dates are accepted for some fields if the exact date cannot be obtained. Fields for which a partial date is accepted are described in the form-specific section of this document. If a partial date is allowed and the exact date is unknown, please enter “UN” (uppercase) for the missing day of the month and select “UNK” for a missing month from the drop-down list. Where dates are expected to be complete, all efforts must be made to obtain missing day/month. If UN is entered into the day for these dates, a non-conformant query will appear. Either the date has to be corrected or a confirmation (e.g. day not known) should be entered in the query response field. Every effort should be made to provide at least the year. The year must always be entered as a valid number. No “UNK” will be accepted. If the year is not known, please leave the whole date blank - in this case don’t enter “UN” for day or “UNK” for month. A query will fire. Please confirm in the query response field that the date is genuinely unknown. If any further relevant information is available, please enter it as a comment on the comment page.






CONFIDENTIAL

Complete dates are expected for:

Form Name Field Name

Visit Visit date

Informed Consents Date informed consent was signed

Washout If Yes, washout start date

IMP Administration and compliance Date of IMP administration

IMP dispense and return If Yes, date of kit handed to subject

IMP dispense and return If Yes, date of kit returned by subject

Unscheduled visit Visit date

Urine Pregnancy Test If Yes, urine pregnancy test date

Adverse Event Start date

Adverse Event Stop Date

Adverse Event If Yes, date of worsening no. 1

Adverse Event If Yes, date of worsening no. 2

Adverse Event Start date of any symptom related to QTcF prolongation

Adverse Event Stop date of any symptom related to QTcF prolongation

End of treatment Date of last administration of IMP

End of trial Date of last contact

End of trial If Yes, date of withdrawal of the informed consent

Time fields Times should be recorded according to the 24-hour clock (e.g., 15:24). Midnight must be entered as “00:00” and with the date of the next day. If the time is not known, leave the field empty. A query will be generated. The site should confirm in the response field that the time is confirmed to be unknown.

Radio Buttons If a question has multiple answer options marked with round “Radio Buttons”, only one answer can be selected. If an answer needs to be de-selected and no answering option should be selected, click into the marked field to remove the answer.






CONFIDENTIAL

Check Boxes If a question has multiple answer options collected by a check box, more than one answer can be selected. If an answer needs to be de-selected and no answering option should be selected, click into the marked field to remove the answer.

Entering comments If a site would like to provide additional information or is requested to do so, e.g., by the Medical Expert, this can be done on the ‘Comments’ form.

Missing data Missing codes (like UN or UNK for unknown) are only set up for specific data fields. All other data fields are required. If there is no data, leave the field blank. A query will be generated requesting the missing data. Confirm in the query response field that data is missing and provide a reason, if possible.

Drop down list boxes

For some fields you must select the answer form a drop-down list with pre-populated text for selection. Data entry can be accelerated if the first letters of the answer are typed in rather than scrolling through the drop-down list.

Derived fields Derived fields (e.g. Date of randomisation) will be filled automatically when the page is saved (transferred from 4 G Clinical IRT system). These items are visible but not changeable.

Derived fields can be identified by the icon.






CONFIDENTIAL

Workflow and Queries Immediately after data has been entered into the form and the “Save” button at the bottom of the page is clicked, a system query will appear right next to the field if there are any discrepancies. The query is highlighted in red/pink, with the icon showing as a question mark. These will also be shown as open queries in the “Task Summary” and “Grid View”. Depending on the type of error (missing data, inconsistent data, etc.) the query text will be a short instruction, or a more detailed explanation of the issue.

If the issue is more complex or the inconsistent data is entered on several pages, more detailed query text will be displayed, with reference to which other page this check is referring to. In this case, please check all pages concerned and correct the data where necessary. In addition, manual queries can be generated by the CRA or Data Manager (Clinipace or LEO). To respond to a query: - either enter/correct the data (and provide an audit reason, e.g. “Data Entry Error” or “Updated

Information”)

- Or, if the data is correct (but not as expected), please leave the data as it is, and confirm the data in the query response field (e.g.: “I confirm this value” or “date is correct”, etc.)

Please remember to click Save once done. The person who raised the query will then either close the answered query or send a re-query, as appropriate. NOTE:

o System queries will only close automatically if the discrepancy is solved. In case the discrepancy is not solved, but a valid comment is present, the Data Manager will close the query manually.

o Manual queries will never close automatically. They will be closed by the Data Manager or CRA, depending on who raised the query.

o If a query is generated on a page which has already been verified by the CRA and signed by the Investigator this page needs to be verified by the CRA and signed by the Investigator again if results in a data change.

o Responses to queries should be made within 5 business days.

Verification Since this study applies targeted Source Data Verification (tSDV) the amount of Source Data Verification (SDV) performed on each subject varies. CRAs will either freeze single items or the whole forms once they have finalized verification.






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Data freeze After the site personnel have entered the data into the eCRF and the CRA has verified the data to ensure compliance and completeness, the CRA will flag the eCRF page as “Frozen”. If only single items on the page were verified only this item should be frozen. Once a page or an item has been frozen, site personnel will not be able to change data. Frozen pages ensure stable/unchangeable data to start cleaning activities by the data manager. If manual queries must be raised the Data Manager or CRA will first unfreeze the page and thus allow the site to make the changes. Afterwards, the CRA will re-verify and freeze the “unfrozen” page again.

Data lock Pages will be flagged by the Data Manager as “Locked” to indicate for all user that all data is clean. In case an item or form would need to be unlocked for any data update, the CRA will inform the data manager who will unlock the item or form, as needed. The CRA will re-verify and freeze the “unfrozen” page again and afterwards, the page will be locked again by the data manager.

Investigator Signature – Approval Process After data for the subject is entered, reviewed, and all discrepancies are resolved, the investigator signs all eCRF pages electronically. He/she confirms that data is complete, accurate and reflects the source documentation. The Sub-Investigator is also authorized to sign eCRF pages electronically if documented in the delegation log. The electronic signature will be created in compliance with the FDA regulation 21 CFR Part 11.






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Instructions for the study-specific eCRF modules

Visit NOTE: The visit date on the Visit form should always be entered first. In the exceptional case when assessments are performed across multiple dates within the same Visit, the Visit Date should be the first date in a visit where any assessments are performed. Visit Date Record the date the visit took place or started using the format day-month-year. A complete date is expected. Visit Type Select if visit was performed as “Site visit” or “Phone/video consultation”. Not done Select if visit was “Not done due to Covid-19” or “Not done” due to another reason. If not done, specify reason Provide a short description of the reason why the visit was not done.

Subject identification NOTE: This form cannot be completed in the RAVE EDC system. Once a subject has been added in the Prancer RTSM system, the subject number and site ID is transferred into Medidata RAVE. The fields on this form are read only and protected and can be identified by the suffix “(Transferred from IRT)”






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Informed consents NOTE: The Informed Consent Form(s) must be signed prior to performing any protocol-related procedures, including but not limited to screening evaluations and initiation of wash-out of treatments listed as exclusion criteria. Date informed consent was signed Record the date when informed consent was signed by the subject in the format day-month-year. A complete date is expected. Has additional informed consent for the storage of remaining material from skin biopsies and blood biomarker samples in biobank been signed? Select either Yes, No. Has additional informed consent for wristband actigraphy been signed? Select either Yes, No, or not applicable. NOTE: Not applicable should be selected for Japanese sites only. All other sites must select either "Yes" or "No". Has additional informed consent for exit interview been signed? Select either Yes, No, or not applicable and provide date the consent was signed if applicable. A complete date is expected. NOTE: Options "Yes" and "No" should be selected for sites from Canada, USA and Germany only. All other sites must select "Not applicable"

Rescreen Is the subject re-screened? Record if the subject is re-screened. Tick either Yes or No. NOTE: Data for “If Yes, Subject identification number from previous screening” will be transferred from 4G’s Prancer RTSM system and cannot be changed within RAVE EDC. This field can be identified by the suffix “(Transferred from IRT)”






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Demographics

Date of Birth (transferred from IRT) This date is transferred from the IRT system and cannot be entered into the eCRF. NOTE: Please ensure the Date of Birth is entered into the IRT system according to local legislation, either as full date of birth, or in the format UN-UNK-YYYY (if only year is allowed), or as UN-MON-YYYY (if collection of month and year is allowed). Any correction to this date would need to be made in the IRT system. Age (transferred from IRT) Age is transferred from IRT and cannot be entered into the eCRF. Any correction to this date would need to be made in the IRT system. Age unit Preset to years (cannot be changed). Sex, determined by investigator (transferred from IRT) This item is transferred from the IRT system and cannot be entered into the eCRF. Any correction to this date would need to be made in the IRT system. Ethnicity self-reported by subject Study participants should self-report ethnicity. Select one of the provided options:

Hispanic or Latino: A person of Cuban, Mexican, Puerto Rican, South

or Central American, or other Spanish culture or origin,

regardless of race.

Not Hispanic or Latino Not reported (not provided or available)






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Race Study participants should self-report race. More than one option can be selected. The following definitions are taken from “FDA Guidance for Industry: Collection of Race and Ethnicity Data in Clinical Trials” and is meant to support the selection of the appropriate race:

White: A person having origins in any of the original peoples of Europe, the Middle East, or North Africa.

Black or African American: A person having origins in any of the black racial groups of Africa.

Asian: A person having origins in any of the original peoples of the Far East, Southeast Asia, or the Indian subcontinent, including e.g. Cambodia, China, India, Japan, Korea, Malaysia, Pakistan, the Philippine Islands, Thailand and Vietnam.

Japanese: A person having origins in any of the original peoples of Japan.

American Indian or Alaska native: A person having origins in any of the original peoples of North and South America (including Central America), and who maintains tribal affiliation or community attachment.

Native Hawaiian or Other Pacific Islander:

A person having origins in any of the original peoples of Hawaii, Guam, Samoa or other Pacific Islands.

Other

If Other, specify Specify other race, that are not covered by the above.






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Washout NOTE: Any medication taken during washout period should be recorded in the Prior and concomitant medication form

Did the subject start a washout period? Tick either Yes or No. If Yes, washout start date Record the date when washout started in the format day-month-year. A complete date is expected. If Yes, reason for entering washout period Tick all criteria which apply.






CONFIDENTIAL

Subject eligibility

Does the subject meet all inclusion criteria and none of the exclusion criteria? Visit 1 (Screening): Record “Yes” if all eligibility criteria that can be fully evaluated at screening were met. The following eligibility criteria can be fully evaluated at screening:

• Inclusion criterion 1






• Exclusion criterion 4

















Record “No” if subject did not meet all eligibility criteria that can be fully evaluated at screening or if subject is not eligible for this study for any other reason.






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Visit 3/Week 0: All eligibility criteria for the study must be evaluated at randomisation. Record “Yes” if all eligibility criteria were met. Record “No” if subject did not meet all criteria or if subject is not eligible for this study for any other reason at the time the subject was enrolled. NOTE: If no, please indicate which inclusion criteria were not met and/or which exclusion criteria were met. Select the appropriate criteria from the drop-down lists. Add additional Log lines if several criteria were not met and/or met. NOTE: Each log line contains an Inclusion and Exclusion criterion selection. If both criteria have been entered, but one criterion was entered by mistake, delete only the one, wrong criterion in the log line. If the complete log line with 2 criteria was deactivated (by mistake), the 2nd criterion should be re-entered.






CONFIDENTIAL

Atopy history Age at onset of AD Please provide age at onset of atopic dermatitis in years. NOTE: Age at onset of AD should capture the correct age when the subject was diagnosed with Atopic Dermatitis. Ensure not to record the current age of the subject for the ‘Age at onset of AD’ data point. NOTE: For a subject to be enrolled in the study, he/she should have a history of AD for ≥ 1 year (Inclusion criteria 4). Unit of age at onset of AD Preset to years (cannot be changed).

• Previous AD treatment – Topical corticosteroids Select either No, Yes, or Unknown. If ‘Yes’ is selected for Topical corticosteroids, then response to Highest potency TCS should be selected from either of the options provided in the drop-down list

Weak (group I) Moderately potent (group II) Potent (group III) Very potent (group IV) Unknown

If ‘Yes’ is selected for Topical corticosteroids, then response to What was the main reason for discontinuing Topical corticosteroids? should be selected by clicking on either of the radio button options

Inadequate efficacy Side effects Medically inadvisable to continue treatment Other

If Other, specify Please provide details for the main reason for discontinuing Topical corticosteroids. If ‘No’ is selected for Topical corticosteroids, then response to What was the main reason for not using Topical corticosteroids previously? should be selected from either of the options provided in the drop-down list

Risk of important side effects generally too high Contraindications to topical corticosteroid use Other

If Other, specify Please provide details for the main reason for not using Topical corticosteroids previously.






CONFIDENTIAL

• Previous AD treatment – Topical calcineurin inhibitors Select either No, Yes, or Unknown. NOTE: Topical Calcineurin inhibitors also includes if the subject has previously used tacrolimus or pimecrolimus If ‘Yes’ is selected for Topical calcineurin inhibitors, then response to What was the main reason for discontinuing Topical calcineurin inhibitors? should be selected by clicking on either of the radio button options

Inadequate efficacy Side effects Other

If Other, specify Please provide details for the main reason for discontinuing Topical calcineurin inhibitors If ‘No’ is selected for Topical calcineurin inhibitors, then response to What was the main reason for not using Topical calcineurin inhibitors previously? should be selected from either of the options provided in the drop-down list

Risk of important side effects generally too high Contraindications to topical corticosteroid use Other

If Other, specify Please provide details for the main reason for not using Topical calcineurin inhibitors

• Previous AD treatment –Cyclosporine Select either No, Yes or Unknown. If ‘Yes’ is selected for Cyclosporine, then response to Was cyclosporine used for more than 12 weeks? should be selected by clicking on either of the radio button options provided – ‘No’ or ‘Yes’ or ‘Unknown’. If ‘Yes’ is selected for Cyclosporine, then response to What was the main reason for discontinuing cyclosporine? should be selected by clicking on either of the radio button options


If Other, specify Please provide details for the main reason for discontinuing cyclosporine






CONFIDENTIAL

If ‘No’ is selected for Cyclosporine, then response to What was the main reason for not using cyclosporine previously? should be selected from either of the options provided in the drop-down list

Risk of important side effects generally too high Contraindications to cyclosporine use Other

If Other, specify Please provide details for the main reason for not using cyclosporine

• Previous AD treatment –Wet wraps Select either No, Yes or Unknown.

• Previous AD treatment –Phototherapy Select either No, Yes or Unknown.

• Previous AD treatment –Other systemic medication (Including previous exposure in clinical trials) Select either No, Yes or Unknown. If ‘Yes’ is selected for Other systemic medication, then the medication should be specified. A new logline should be created for each individual systemic medication, and What was the main reason for discontinuing other systemic medication? should be selected by clicking on either of the radio button options


If Other, specify Please provide details for the main reason for discontinuing cyclosporine






CONFIDENTIAL

Medical and surgical history

Please document in this module any relevant diseases the subject had in the past as well as any relevant diseases present at the time the subject signed informed consent. Also record any relevant chronic conditions that are intermittent or recurrent in nature. NOTE: Any medications related to the condition or diagnosis should be recorded in the Prior and concomitant medication form

NOTE: Do not report the indication of the study disease (atopic dermatitis). After signing the Informed Consent any worsening of a pre-existing disease/illness or newly emergent disease/illness between Informed Consent and randomization must be reported as medical history. Any worsening of a pre-existing disease/illness or newly emergent disease/illness after randomization must be reported as an adverse event. The medical history page must be consistent with clinically relevant abnormal findings in the physical examination, vital signs, laboratory results, other clinical evaluations, and entries on the prior/concomitant medication form. To record more than one medical conditions/diagnoses/procedures, click on the ‘Add a new Log line’ link. Does the subject have any concurrent diagnoses or relevant medical or surgical history within the previous 12 months? If the subject has either experienced any relevant medical history since birth and/or any other medical or surgical history including concurrent diagnoses within the previous 12 months, select “Yes” and complete the following section with details of appropriate conditions or diagnoses and consider the impact on the inclusion/exclusion criteria. Otherwise, select “No” and leave the page blank. NOTE: If yes, please complete the following section with details of appropriate conditions or diagnoses and consider the impact on the inclusion/exclusion criteria.

NOTE: If response for ‘Does the subject have any concurrent diagnoses or…?’ is No, then all the fields in the Log Lines will become inactive so data cannot be entered. Condition or diagnosis

• Record all relevant past and/or concomitant medical conditions and past surgeries, as defined in the protocol.

• Record only one condition or surgery per line.

• When recording a condition and surgery related to that condition, use one line for the condition and one line for the surgery.

• Ensure that any of the conditions listed on the Medical History page does not violate the in-/exclusion criteria.

• If multiple signs/symptoms can be captured by a single diagnosis, enter only that single diagnosis.

• Recording of diagnoses is preferred to describing which values were out of range (e.g., record “hypercholesterolemia” instead of “high blood cholesterol level”).

• Do not use abbreviations






CONFIDENTIAL

Medical and surgical history - continued Start date Specify since when the subject has experienced this condition or diagnosis the first time. If the exact date is unknown, please enter “UN” (uppercase) for the missing day of the month and select “UNK” for a missing month from the drop-down list. NOTE: Partial dates accepted, but every effort should be made to provide at least month and year. Stop date If this condition resolved before enrollment into the study, specify the date since when the condition was considered to be resolved. If the exact date is unknown, please enter “UN” (uppercase) for the missing day of the month and select “UNK” for a missing month from the drop-down list. NOTE: Partial dates accepted, but every effort should be made to provide at least month and year. Ongoing Select ‘Yes’ if the condition is still present at the time of the assessment. Otherwise select ‘No’. NOTE: Controlled underlying conditions (e.g. hypertension that is controlled by medication) may be considered as “ongoing” even though no symptoms may be present at the time the medical history is recorded.






CONFIDENTIAL

Eczema area and severity index (EASI) NOTE: EASI will be assessed by the investigator based on the condition of the disease at the time of evaluation and not in relation to the condition at a previous visit.

Body region: Preset to Head/Neck, Trunk, Upper extremities, Lower extremities (cannot be changed). NOTE: The following needs to be reported for each of the four body regions: NOTE: Half-scores 1.5 and 2.5 are allowed Erythema Select one of the following:

0 None/absent 1 Mild 1.5 2 Moderate 2.5 3 Severe

Induration/papulation Select one of the following:


Excoriation Select one of the following:







CONFIDENTIAL

Eczema area and severity index (EASI) - continued Lichenification Select one of the following: 0 None/absent 1 Mild 1.5 2 Moderate 2.5 3 Severe Area score Select one of the following:

0 0% affected area 1 1% to 9% affected area 2 10% to 29% affected area 3 30% to 49% affected area 4 50% to 69% affected area 5 70% to 89% affected area 6 90% to 100 affected area

Weighting Factor (x 0.1, x 0.3, x 0.2, x 0.4) Will be used for calculating the Score depending on the body regions selected. Score Will be calculated in Rave EDC automatically Total EASI score Will be calculated in Rave EDC automatically.






CONFIDENTIAL

Validated investigator global assessment (vIGA-AD) NOTE: vIGA-AD will be assessed by the investigator and is based on a 5-point scale ranging from 0 (clear) to 4 (severe) The assessment will be based on the condition of the disease at the time of evaluation and not in relation to the condition at a previous visit. Validated Investigator Global Assessment (vIGA-AD) Select one of the following:

0 Clear No inflammatory signs of atopic dermatitis (no erythema, no induration/papulation, no lichenification, no oozing/crusting). Post-inflammatory hyperpigmentation and/or hypopigmentation may be present.

1 Almost Clear Barely perceptible erythema, barely perceptible induration/papulation, and/or minimal lichenification. No oozing or crusting.

2 Mild Slight but definite erythema (pink), slight but definite induration/papulation, and/or slight but definite lichenification. No oozing or crusting.

3 Moderate Clearly perceptible erythema (dull red), clearly perceptible induration/papulation, and/or clearly perceptible lichenification. Oozing and crusting may be present.

4 Severe Marked erythema (deep or bright red), marked induration/papulation, and/or marked lichenification. Disease is widespread in extent. Oozing and crusting may be present.






CONFIDENTIAL

Scoring atopic dermatitis (SCORAD)

NOTE: SCORAD will be assessed by the investigator based on the condition of the disease at the time of evaluation and not in relation to the condition at a previous visit.

Extent, please indicate the area involved

Please indicate the area involved.

Unit for extent Unit is pre-set: %

Erythema Select one of the following:

0 None/absent 1 Mild 2 Moderate 3 Severe

Edema/papulation Select one of the following:


Oozing/crusting Select one of the following:


Excoriation Select one of the following:


Lichenification Select one of the following:







CONFIDENTIAL

Scoring atopic dermatitis (SCORAD) - continued

Dryness Select one of the following:


Pruritus Numerical entry in the range 0-10, where 0 means no itching and 10 means unbearable itching. Sleep loss Numerical entry in the range 0-10, where 0 means no trouble sleeping and 10 means a lot of trouble sleeping. Subjective symptoms (pruritus + sleep loss) Will be calculated in Rave EDC automatically. SCORAD Score Will be calculated in Rave EDC automatically.






CONFIDENTIAL

Physical Examination Was the physical examination performed? If physical examination was performed select “Yes”, otherwise select “No”. If No, specify reason Record an explanation why physical examination was not done. If Yes, result Record the result of the examination (e.g., ‘Normal’, ‘Abnormal, not clinically significant’, ‘Abnormal, clinically significant’). If Abnormal, clinically significant, Please complete Medical and surgical history form and specify MH number. NOTE: If AD (Atopic dermatitis) is the only abnormality found, Physical examination should be assessed as Normal and AD should not be reported on the Medical and Surgical History form.

Physical Examination 2 Was the physical examination performed? If physical examination was performed select “Yes”, otherwise select “No”. If No, specify reason Record an explanation why physical examination was not done. If Yes, result Record the result of the examination (e.g., ‘Normal’, ‘Abnormal, not clinically significant’, ‘Abnormal, clinically significant’). If Abnormal, clinically significant, Please complete Adverse event form and specify AE number. NOTE: If AD (Atopic dermatitis) is the only abnormality found, Physical examination should be assessed as Normal and AD should not be reported on the Adverse event form unless it is a significant deterioration (Protocol, section 13.6.4).






CONFIDENTIAL

Vital Signs NOTE: Vital signs should be measured following at least 5 min of rest. Were vital signs performed? Indicate if the vital signs were collected. If “Yes”, include the appropriate details, where indicated on the eCRF. If No, specify reason Record an explanation why vital signs were not done. Record vital signs results in the unit pre-set on the eCRF for

• Systolic blood pressure (mmHg)

• Diastolic blood pressure (mmHg)

• Pulse (beats/min)

• Temperature (record result of measurement with 1 decimal place)

• Unit temperature (please select as unit for temperature Celsius or Fahrenheit, as appropriate)

NOTE: Abnormal clinically significant vital signs at screening and baseline will be documented as medical history in the eCRF Please complete the Medical and surgical history form. At subsequent visits, any new abnormal clinically significant vital signs, symptoms, or illnesses, as well as any clinically significant deterioration of a pre-existing condition after randomization will be reported as an AE. Please complete Visit AE/CM/CP events and then complete the Adverse Event form.






CONFIDENTIAL

ECG Were ECG assessments performed for all timepoints? Indicate whether or not ECG assessments were done.

If No, specify Reason Provide a short explanation, why the ECG assessments were not performed. If part of the per protocol expected ECGs are not taken, it should clearly be stated which ECGs were not taken, and the reason why.

If Yes, results Record the interpretation from the Investigator as either:

• Normal

• Abnormal, not clinically significant

• Abnormal, clinically significant

NOTE: If Abnormal, clinically significant was selected, please document this finding on Medical and surgical history form first and then select the corresponding MH number from drop-down menu.

ECG 2 Were ECG assessments performed for all timepoints? Indicate whether or not ECG assessments were done.

NOTE: If visit is remote due to COVID-19 and local ECG has been taken, this should be “yes” and a comment should be made in the comments log stating that local safety ECG was taken.

If No, specify Reason Provide a short explanation, why the ECG assessments were not performed. If part of the per protocol expected ECGs are not taken, it should clearly be stated which ECGs were not taken, and the reason why.

If Yes, results Record the interpretation from the Investigator as either:

• Normal



NOTE: Any clinically significant deterioration of a pre-existing condition as well as any new clinically significant abnormality should be documented as either MH (for ECGs taken before first IMP administration) or AE (for ECGs taken after first IMP administration). As applicable, either fill in the Medical and surgical history form and then select the corresponding MH number from drop-down menu or complete the Adverse event form and then select the corresponding AE number from drop-down menu.

NOTE: Any "clinically relevant" ECG findings must be collected as AEs.






CONFIDENTIAL

Central laboratory Was blood sampling performed Indicate whether or not lab specimen was collected. NOTE: If Yes, please ensure that blood samples have been sent to the central lab. If No, specify reason: Provide a short explanation why blood sampling was not performed. If Yes, result Indicate if the result is

• Normal



NOTE: If Abnormal, clinically significant was selected, please document this finding as Medical History. Please complete the Medical and surgical history form and then select the corresponding Medical History number from drop-down menu. Was a urine sample tested with a dipstick? Select Yes or No. If No, specify reason: Provide a short explanation why urine was not tested. If Yes, based on dipstick result and judgement by investigator is a Urinalysis required? Select either Yes or No. NOTE: If Yes, send urine sample to the central laboratory for urinalysis. If Yes, result Indicate if the result is

• Normal


• Abnormal, clinically significant NOTE: If Abnormal, clinically significant was selected, please document this finding as Medical History. Please complete the Medical and surgical history form and then select the corresponding Medical History number from drop-down menu.






CONFIDENTIAL

Central laboratory 2 Was blood sampling performed Indicate whether or not lab specimen was collected. NOTE: If Yes, please ensure that blood samples have been sent to the central lab. If No, specify reason: Provide a short explanation why blood sampling was not performed. If Yes, result Indicate if the result is

• Normal



NOTE: Any clinically significant deterioration of a pre-existing condition as well as any new clinically significant finding should be documented as an AE. Please complete AE form first and then select the corresponding AE number from drop-down menu. Was a urine sample tested with a dipstick? Select Yes or No. For Visit 2 (Screening/run-in) please select No. If No, specify reason: Provide a short explanation why urine was not tested. For Visit 2 (Screening/run-in) please enter, e.g. “not required by protocol”. If Yes, based on dipstick result and judgement by investigator is a Urinalysis required? Select either Yes or No. NOTE: If Yes, send urine sample to the central laboratory for urinalysis. If Yes, result Indicate if the result is

• Normal


• Abnormal, clinically significant NOTE: Any clinically significant deterioration of a pre-existing condition as well as any new clinically significant finding should be documented as an AE. Please complete AE form first and then select the corresponding AE number from drop-down menu






CONFIDENTIAL

Actigraphy NOTE: Only for subjects participating in this optional component of the study.

NOTE: Form is only available if triggered by the informed consent form

Which of the subject’s hand is dominant? Please indicate, if the left or right hand is dominant Actigraphy device number (Left hand/Right hand) Please specify actigraphy device number for the respective hand.

Actigraphy 2 NOTE: At subsequent visits, please enter the data for the respective hand NOTE: Form is only available if triggered by the informed consent form NOTE: According to the protocol, the device worn on the subject’s dominant wrist should as a minimum be worn during the subject’s main sleep period while the device worn on the subject’s non-dominant wrist should be worn at all times. Did the subject wear the device as instructed? Indicate, if yes or no. If No, Specify reason Provide a short explanation why data why not. Were the data downloaded? (Left hand/ Right hand) Indicate, whether or not data were downloaded for the respective hand. If No, Specify reason Provide a short explanation why data were not downloaded. Was a new actigraphy device provided to the subject? Indicate, if yes or no. If Yes, provide actigraphy device number






CONFIDENTIAL

Body measurements Height Height measured without shoes. Record the height according to the unit (select either cm or in). Unit height Select the appropriate unit (either cm or in). Weight Weight measured in indoor clothing and without shoes. Record the weight according to the unit (either kg or lb). Unit weight Select the appropriate unit (kg or lb).

Fasting Did the subject fast as per protocol? Tick either Yes or No.

Urine pregnancy test Is the female of child-bearing potential? Indicate, whether or not the female is of child-bearing potential. If Yes, was a urine pregnancy test performed? Indicate, whether or not the urine pregnancy test has been performed. If No, Specify reason Provide a reason why the pregnancy test was not performed. NOTE: If no urine pregnancy test has been performed on a scheduled visit, an unscheduled pregnancy test should be done immediately and documented as an unscheduled visit. If Yes, urine pregnancy test date Record the date when specimen collection occurred using the format day-month-year. If Yes, result Record test result either Positive or Negative. NOTE: If the result of Urine Pregnancy Test is found ‘Positive’ at any time during the study, the subject must discontinue IMP immediately. In addition, a positive result of the urine pregnancy test must be verified by a serum pregnancy test. Please collect blood lab sample and send it to central laboratory (ACM).






CONFIDENTIAL

Additional PK due to QTcF prolongation NOTE: Only in case of moderate (480 ms < average QTcF =< 500 ms or 30 ms < increase in QTcF from baseline <= 60 ms ) or severe (Average QTcF > 500 ms or increase in QTcF from baseline > 60 ms ) QTcF prolongation at visits 5, 7, 9 and 11 an additional PK must be performed. Is additional PK needed at this visit due to QTcF prolongation? Tick either Yes or No NOTE: If Yes is ticked, the PK form appears dynamically.

Pharmacokinetics Was PK sampling performed for all timepoints? Tick either Yes or No If No, Specify reason Note: Provide a reason why the PK sampling was not performed for all timepoints, and specify clearly which PK samples were not performed

Blood biomarkers Was sampling performed for blood biomarkers? Tick either Yes or No If No, Specify reason Provide a reason why the sampling for blood biomarkers was not performed.






CONFIDENTIAL

Skin biopsy – lesional, non-lesional Note: Subjects who have lesions at a location suitable for a biopsy will be asked if they agree to provide skin biopsies. Was skin biopsy taken from lesional area? Select either Yes or No. If No, specify reason Provide a short explanation why skin biopsy was not performed. If Yes, indicate body location Select the body location . If Other, specify . Was skin biopsy taken from non-lesional area? Select either Yes or No. If No, specify reason Provide a short explanation why tape stripping was not performed. If Yes, indicate body location Select the body location . If Other, specify

Skin biopsy – lesional NOTE: Subjects who have lesions at a location suitable for a biopsy will be asked if they agree to provide skin biopsies. Was skin biopsy taken from lesional area? Select either Yes or No. If No, specify reason Provide a short explanation why skin biopsy was not performed. If Yes, indicate body location Select the body location. If Other, specify






CONFIDENTIAL

Randomisation Was the subject randomised? Select either Yes or No. Date of randomization Date will be transferred from IRT. Age NOTE: Age only to be collected if not full date of birth is collected on the demographics form. Age on the day of randomization. Age unit Preset to years (cannot be changed).






CONFIDENTIAL

IMP administration and compliance Did the subject take the IMP at the site? Please enter Yes or No. If No, specify reason Provide a short explanation why IMP was not taken at the site. If taken in error in the morning before the site visit, the reason “medication taken in error before site visit” should be given. Date of IMP administration Record the date of IMP administration using the format day-month-year. A complete date is expected. Time of IMP administration Record the time of IMP administration using 24-hour clock.






CONFIDENTIAL

IMP dispense and return Kit number (transferred from IRT) This item is transferred from the IRT system. Visit/Week Tick Visit/Week when IMP was dispensed. Kit handed to subject Please tick Yes or No. If Yes, date of kit handed to subject Record the date the IMP kit was handed to subject using the format day-month-year. A complete date is expected. If Yes, kit returned? Please enter Yes or No. If Yes, date of kit returned by subject Record the date the IMP kit was returned by subject using the format day-month-year. A complete date is expected. NOTE: Half-dose taken by the subject is to be regarded a missed dose and should not be counted. If Yes, number of morning doses Record the number of morning doses the subject has taken. If Yes, number of evening doses taken Record the number of evening doses the subject has taken.






CONFIDENTIAL

Early Termination NOTE: This page has only to be completed in case a subject is stopping IMP prematurely. It is not required to terminate the trial at the same time.

Select the visit at which the subject is being early terminated.

• Visit 3/Week 0

• Visit 4/Week 1

• Visit 5/Week 2

• Visit 6/Week 4

• Visit 7/Week 6

• Visit 8/Week 8

• Visit 9/Week 10

• Visit 10/Week 12

• Visit 11/Week 14

• Unscheduled visit

AE/CM/CP events Did the subject have any adverse events since screening? Indicate whether the subject had any adverse events since screening. Select either “Yes” or “No”. NOTE: If “Yes” is selected the form “Adverse event” will be visible for data entry. Did the subject take any prior and concomitant medications? Indicate whether the subject took any concomitant medications or vaccines from 3 months prior to screening through safety follow-up period. Select either “Yes” or “No”. NOTE: If “Yes” is selected the form “Prior and concomitant medication” will be visible for data entry. Did the subject have any concurrent procedures/surgeries since screening? Indicate whether the subject had any concurrent procedures/surgeries from 3 months prior to screening through safety follow-up period. Select either “Yes” or “No”. NOTE: If “Yes” is selected the form “Concurrent procedures” will be visible for data entry.






CONFIDENTIAL

Adverse Event

Observation / reporting period for AEs All adverse events starting between informed consent and end of study (as defined in section 7.3 in the study protocol) should be recorded.

NOTE: Adding new pages for additional adverse events: Select the subject and the appropriate form (Adverse Event) and use the “Add a new Log line” button to enter additional adverse events.

NOTE This form contains all questions related to the three trial AESI. Only applicable data points should be filled in. All other data points can be left blank.

Adverse Event Record only one diagnosis, sign, or symptom per page (e.g., nausea and vomiting should not be recorded in the same entry, but as two separate entries). Use accepted medical terminology, enter the diagnosis (if known); otherwise enter a sign or symptom. If a diagnosis subsequently becomes available, then this diagnosis should be entered on the AE form, replacing the original entries, where appropriate. Death should not be recorded as an event but should be recorded as the outcome of the event unless cause is unknown. The condition that resulted in the death should be recorded as the event. Do not use abbreviations. Surgeries / interventions should not be recorded as adverse events, rather the medical condition requiring the surgery / intervention. NOTE: AEs reported during the trial that are considered related to the COVID-19 vaccine should be recorded as “xxx related to COVID-19 vaccine”. Start Date Record the start date of the AE using the format day-month-year. The start date specifies the first occurrence (observation). A complete date is required. If the exact date is not known, specify the earliest possible date. The start date must be between the date of informed consent and end of study. NOTE: If the event is a worsening of a medical history after administration of IMP, the start date to be added is the date of worsening. Did the adverse event start before the first administration of IMP? Indicate whether the adverse event started before the first administration of the IMP. Select either “Yes” or “No”. The first administration is the administration at Visit 3/Week 0.






CONFIDENTIAL

Adverse Event -continued Stop Date Record the date that the AE resolved using the format day-month-year. If the AE is ongoing (either recovering/resolving or not recovered/not resolved), leave the field blank. NOTE: If the adverse event resolves during the course of the trial, please insert the applicable stop date and update "ongoing" to "No". Ongoing Indicate whether the adverse event has not resolved at the time of data collection. Select either “Yes” or “No”. If yes, leave the Stop Date blank. NOTE: If the adverse event resolves during the course of the trial, please update "ongoing" to "No" and insert the applicable stop date. Severity at onset The severity at the onset of the AE should be described in terms of mild, moderate or severe according to the investigator’s clinical judgement. Tick the appropriate box:

• Mild: An AE that is usually transient and may require only minimal treatment or therapeutic intervention. The event does not generally interfere with usual activities of daily living.

• Moderate: An AE that is usually alleviated with additional specific therapeutic intervention. The event interferes with usual activities of daily living, causing discomfort but poses no significant or permanent risk of harm to the subject.

• Severe: An AE that interrupts usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention

Did the event worsen in severity after onset? Select either “Yes” or “No”. NOTE: If the AE worsens in severity, the new severity including date of worsening should be recorded. However, if an AE with onset prior to IMP initiation worsens after first dose of IMP,a new AE should be recorded If Yes, Worsening no. 1 Indicate “Moderate” or “Severe” If Yes, Date of worsening no. 1 A complete date is required. If Yes, Worsening no. 2 (Only to be completed in situations with more than one worsening) If the severity continues to worsen, please select “Severe” If Yes, Date of worsening no. 2 (Only to be completed in situations with more than one worsening. A complete date is required.






CONFIDENTIAL

Adverse Event -continued Was the AE related to IMP? Indicate whether the AE is related to IMP. Tick the appropriate box:

• Probably related: Follows a reasonable temporal sequence from administration of the IMP. Could not be reasonably explained by the subject’s clinical state, environmental or toxic factors or other therapies administered to the subject. Follows a known pattern of response to the IMP. Disappears or decreases on cessation or reduction in dose of the IMP. Reappears or worsens upon re-challenge.

• Possibly related: Follows a reasonable temporal sequence from the administration of the IMP. Could also be reasonably explained by the subject’s clinical state, environmental or toxic factors or other therapies administered to the subject. Follows a known pattern of response to the IMP.

• Not related: Does not follow a reasonable temporal sequence from administration of the IMP. Is better explained by other factors like the subject’s clinical state, environmental or toxic factors or other therapies administered to the subject. Does not reappear or worsen upon re-challenge. Does not follow a known pattern of response to the IMP.

Action Taken with IMP Any action taken with the IMP as a consequence of the AE must be recorded. Tick the appropriate box: Select ’Drug interrupted’ if the IMP is temporarily discontinued Select 'Drug withdrawn' if the IMP is permanently discontinued.

• Dose not changed

• Drug interrupted

• Drug withdrawn

• Not applicable

• Unknown Other action taken (tick all that apply) Any other action taken as a result of the AE must be recorded. Tick all that apply:

• None

• Prior and concomitant medication

• Concurrent procedure Withdrawn from trial due to this AE? It must be recorded whether the AE led to withdrawal from the trial. Select either “Yes” or “No”. NOTE: If the subject was withdrawn, all further protocol-defined activities should be stopped with the exception of the early termination visit and safety follow-up.






CONFIDENTIAL

Adverse Event -continued Was the AE serious? Assess if an adverse event should be classified as serious based on the “serious” criteria defined in the protocol. Select either “Yes” or “No”. SAE criteria (tick all that apply)

• Death

• Life threatening

• In-patient hospitalisation/prolongation of existing hospitalisation

• Persistent or significant disability/incapacity

• Congenital anomaly or birth defect

• Other medically important condition

The completed paper SAE form must be faxed or scanned and e-mailed to Global Pharmacovigilance at LEO using the e-mail address or fax number below immediately, without undue delay and no later than 24 hours: Global Pharmacovigilance at LEO E-mail address: [email protected] Fax number: +45 7226 3287

Outcome The outcome of the event according to the investigator’s clinical judgement should be classified using the categories below. Record the appropriate outcome of the event in relation to the subject’s status at the end of the study. If the subject died, only the AE representing the underlying cause of death should have the outcome ‘fatal’; all other AEs that were present at the time of death should be reported as ‘not resolved’. Record the stop date if the AE has the outcome ‘Recovered/resolved’, ‘Recovered/resolved with sequelae’ or ‘Fatal’.

• Fatal: The subject has died as a consequence of the event. Date of death is recorded as stop date for the AE.

• Not recovered/not resolved: Event is still ongoing.

• Recovering/resolving: The subject is clearly recovering from an event. The event is not yet completely resolved.

• Recovered/resolved: The event has stopped. The stop date of the event must be recorded.

• Recovered/resolved with sequelae: The event has reached a state where no further changes are expected, and the residual symptoms are assumed to persist. An example is hemiparesis after stroke. The stop date of the event must be recorded.

• Unknown: Unknown to investigator, e.g., subject lost to follow-up.

mailto:[email protected]






CONFIDENTIAL

Adverse Event -continued (AESI) Is the event an adverse event of special interest? Defined adverse events of special interest (AESI) in this study are "Eczema herpeticum", “Skin infections requiring systemic treatment” and “Electrocardiogram QT corrected interval prolongation (QTcF prolongation)”. If the subject experiences such an event, please tick Yes and complete below. If the AE is not one of the above, tick No.

Adverse of special interest Additional information regarding applicable AESI. Select either "Eczema herpeticum", “Skin infections requiring systemic treatment” or “Electrocardiogram QT corrected interval prolonged (QTcF prolongation)”. NOTE: Only the applicable AESI questions need to be filled in. The rest can be left as blank.

AESI Eczema herpeticum:

If Eczema herpeticum, Skin findings – Location (tick all that apply) Tick all that apply: Face, Scalp, Back, Chest, Upper limb, Lower limb, Genitals

If Eczema herpeticum, Skin findings – Presence Indicate: Present in area with visible eczema, Present in area with no visible eczema, Present in area with or without visible eczema

If Eczema herpeticum, Skin findings – Morphology Indicate: Monomorphic or Polymorphic

If Eczema herpeticum, Skin findings – Lesion type (tick all that apply) Tick all that apply: Papules, Vesicles, Crusts, Eroded pits, Other If Other, specify If Eczema herpeticum, Skin findings – Dissemination Indicate: Localised or Disseminated within one or more regions






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Adverse Event -continued (AESI) If Eczema herpeticum, Skin findings – Confirmation of Herpes simplex virus (tick all that apply) Tick all that apply: Not confirmed, Polymerase chain reaction (PCR), Viral culture, Tzanck, Other If Other, specify

AESI Skin infections requiring systemic treatment: If Skin infections requiring systemic treatment, Location (tick all that apply) Tick all that apply: Face, Scalp, Back, Chest, Upper limb, Lower limb, Genitals

If Skin infections requiring systemic treatment, Outcome pathogenic skin swab Indicate: Positive, Negative or Not performed If positive, tick all that apply Tick all that apply: Staphylococcus aureus, Streptococcus, Candida, Other If Other, specify

AESI QTcF prolongation

If QTcF prolongation, QTcF severity The QTcF severity should be described in terms of mild, moderate or severe according to the investigator’s clinical judgement. Tick the appropriate box:

• Mild: 450 ms (men) or 460 ms (women) < average QTcF =< 480 ms.

• Moderate: 480 ms < average QTcF =< 500 ms or 30 ms < increase in QTcF from baseline <= 60 ms.

• Severe: Average QTcF > 500 ms or increase in QTcF from baseline > 60 ms.

If QTcF prolongation, did the subject experience any related symptoms? Indicate: No or Yes If Yes, tick all that apply Tick all that apply: Heart palpitations, Shortness of breath, Chest pain, Light headedness, Dizziness, Other If Other, specify






CONFIDENTIAL

Adverse Event -continued (AESI)

NOTE: For any experienced symptom (Heart palpitations, Shortness of breath, Chest pain, Light headedness, Dizziness, Other) please specify start and stop date and if less than one day, specify how many hours the subject experienced this symptom. Symptoms of the QT prolongation should only be captured here, and not as separate events If Heart palpitations, Start date A complete date is required. If Heart palpitations, Stop date A complete date is required. If less than one day, How many hours did the subject experience this symptom? Enter the number of hours the subject experienced heart palpitations. Unit Preset to hours (cannot be changed). If Shortness of breath, Start date A complete date is required. If Shortness of breath, Stop date A complete date is required. If less than one day, How many hours did the subject experience this symptom? Enter the number of hours the subject experienced shortness of breath. Unit Preset to hours (cannot be changed).

If Chest pain, Start date A complete date is required.

If Chest pain, Stop date A complete date is required.

If less than one day, How many hours did the subject experience this symptom? Enter the number of hours the subject experienced chest pain.

Unit Preset to hours (cannot be changed).

If Light headedness, Start date A complete date is required.






CONFIDENTIAL

Adverse Event -continued (AESI)

If Light headedness, Stop date A complete date is required. If less than one day, How many hours did the subject experience this symptom? Enter the number of hours the subject experienced light headedness. Unit Preset to hours (cannot be changed). If Dizziness, Start date A complete date is required.

If Dizziness, Stop date A complete date is required. If less than one day, How many hours did the subject experience this symptom? Enter the number of hours the subject experienced dizziness.

Unit Preset to hours (cannot be changed). If Other symptom, Start date A complete date is required.

If Other symptom, Stop date A complete date is required.

If less than one day, How many hours did the subject experience this symptom? Enter the number of hours the subject experienced other symptom.

Unit Preset to hours (cannot be changed).






CONFIDENTIAL

Prior and concomitant medication

Any medication or vaccine that the subject receives from 3 months prior to screening through to safety follow-up must be recorded in the subject’s medical record and the eCRF.

Adding new pages for additional prior/concomitant medication: Select the subject and the appropriate form (Concomitant medication) and use the “Add a new Log line” button to enter additional concomitant medications.

NOTE: Record ONLY one medication per line. NOTE: Emollients are not considered concomitant medication and should not be recorded as such. NOTE: Each dose of COVID-19 vaccination should be recorded as a single concomitant medication.

All additions to or changes in medications (prescriptions or over-the-counter medications) after enrollment must also be recorded on these pages.

• Medication or therapy (generic or brand name) Preferably, the generic name should be recorded; otherwise, the brand name may be recorded. Do not enter non-drug treatments on this page.

• Indication Please record the primary indication, select either “Adverse Event”, “Medical and surgical history” or “Other Indication”: NOTE: The Study indication “Atopic dermatitis” is no “Medical and surgical history”. Please tick “Other indication” and specify the indication in “if Other indication, please specify”.

• If Adverse event, please complete AE form and specify AE number.

NOTE: Ensure that the dates on the adverse events pages are consistent. ‘Concomitant medication’ given as Other action taken for the adverse event must be indicated for the corresponding adverse event on the adverse events pages (AE). NOTE: If the reported AE term or start date is updated on the AE form after the Concomitant Medication has been ‘linked’ to this AE, a non-conformant flag appears on the Concomitant Medication page and the user is requested to update the ‘link’ to reflect the latest entry on the AE form.






CONFIDENTIAL

Prior and concomitant medication - continued

• If Medical or surgical history, please complete MH form and specify MH number

NOTE: Ensure that the dates on the Medical and surgical history forms are consistent.

NOTE: If the reported MH term or start date is updated on the Medical History form after the Concomitant Medication has been ‘linked’ to this MH, a non-conformant flag appears on the Concomitant Medication page and the user is requested to update the ‘link’ to reflect the latest entry on the Medical History form.

• If Other indication is ticked, please provide a short explanation of other indication, e.g. “COVID-19 vaccination” or “Atopic Dermatitis”






CONFIDENTIAL


• Start Date Record the date the medication or therapy was first taken using the format day-month-year. If the subject has been taking the medication for a considerable amount of time prior to the start of the study, it is acceptable to have an incomplete date. Medications taken during the study are expected to have a complete start date. Prior medications that are exclusionary should have both a start and stop date.

• Stop Date Record the date the subject stopped taking the medication using the format day-month-year. If the subject has not stopped taking the medication leave this field blank.

• Ongoing Record the medication as ongoing if the subject has not stopped taking the medication or therapy at the time of data collection. The end date should be left blank. Select either “Yes” or “No”.

• Is this medication or therapy a rescue medication for atopic dermatitis? Indicate whether this medication or therapy is a rescue medication for the atopic dermatitis. Select either “Yes” or “No”. Please select "Yes" only if the rescue medication was administered after randomization.

NOTE: Rescue treatment for AD may be provided to the subject at the discretion of the investigator if medically necessary (i.e. to control intolerable worsening of AD symptoms).

If Yes, for what primary reason was the rescue medication for atopic dermatitis given? Record the primary reason

• Lack of efficacy on itch

• Lack of efficacy on visible AD symptoms NOTE: Visible AD symptoms such as erythema, papules, excoriations, swelling, etc.

• Lack of efficacy on both itch and visible AD symptoms

• Other

If Other, specify Specify primary reason that is not covered by the above.

• Dose per administration Record the dose of the medication taken per administration (e.g., 200).






CONFIDENTIAL


• Unit Record the dose unit of the dose of the medication taken. Tick the appropriate box:

• mcg

• mg

• g

• mL

• Application

• International Unit (IU)

• Tablet

• Capsule

• Other

If Other, specify Specify unit that is not covered by the above.

• Frequency Record how often the medication or therapy was taken. Tick the appropriate box:

• As needed (PRN)

• Daily (QD)

• Twice daily (BID)

• Three times per day (TID)

• Four times per day (QID)

• Weekly (QS)

• Monthly (QM)

• Once

• Other

If Other, specify Specify frequency that is not covered by the above.






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• Route Provide the route of administration for the drug. Tick the appropriate box:

• Oral

• Cutaneous

• Subcutaneous

• Transdermal

• Ophthalmic

• Intramuscular

• Respiratory (inhalation)

• Intralesional

• Intraperitoneal

• Nasal

• Vaginal

• Rectal

• Intravenous

• Other

If Other, specify Specify route that is not covered by the above.

NOTE: If there was a change in dosage, regimen or route, enter the stop date and record the changed medication as a new medication in a new log line. Verify that ‘Start’ and ‘Stop’ dates of consecutive records for the same medication do not overlap. Verify the concomitant medication with regards to prohibited medication.






CONFIDENTIAL

Concurrent procedures Any concurrent procedure that the subject had from 3 months prior to screening (if relevant) through follow-up period must also be recorded in the subject’s medical record and the eCRF. Procedure name (include anatomical area if relevant) Record only one procedure per line and include anatomical area if relevant. Indication Record the primary indication for this procedure (Adverse Event, Medical and surgical history, or Other indication). NOTE: If indication is Adverse Event or Medical and surgical History please complete AE or Medical and surgical history form Start Date Record the date of the procedure using the format day-month-year. If the procedure started for a considerable amount of time prior to the start of the study, it is acceptable to have an incomplete date. Procedures started during the study are expected to have a complete start date.

Stop Date Record the date the procedure stopped using the format day-month-year. If the procedure has not stopped leave this field blank. Ongoing Record the procedure as ongoing if it has not stopped at the time of data collection. The end date should be left blank. Select either “Yes” or “No”.






CONFIDENTIAL

Unscheduled Visit On the subject casebook homepage please click on the ‘Add event’ drop-down box and select the Unscheduled Visit to be added for entry and save.

This will trigger the Unscheduled visit – type of assessment page.

The reason for the Unscheduled visit should be selected. If Adverse event/safety is selected, please record the Adverse event as appropriate. The "Unscheduled Visit" is a folder where all additional examinations should be recorded, regardless of when they were done. This visit in the eCRF is not a complete/normal visit, i.e. not all eCRF pages need to be entered (e.g. if only additional vital signs were measured, please only enter an additional vital signs eCRF page). Visit (Unscheduled) page: Visit Date Record the date the unscheduled visit took place or started using the format day-month-year. A complete date is expected. Visit type Select either Site visit or Phone/video consultation.






CONFIDENTIAL

Unscheduled - type of assessment Reason for unscheduled visit Record the reason for the unscheduled visit (select all that apply)

• Atopic dermatitis flare

• Adverse event/safety

• Unscheduled IMP dispensing

• Due to Covid-19

• Other If Other, specify any reason, that is not covered by the above.

Type of assessment (select all that apply) Record the Type of assessment. Select all that apply. NOTE: Corresponding eCRF pages will be triggered by type of assessment ticked.

• Validated Investigators Global Assessment (vIGA-AD)

• Eczema area and severity index (EASI)

• Scoring atopic dermatitis (SCORAD)

• Vital signs

• Physical examination – screening

• Physical examination 2 – subsequent visits after screening

• Fasting

• ECG - screening

• ECG 2 - subsequent visits after screening

• Urine pregnancy test

• Central laboratory - screening

• Central laboratory 2 - subsequent visits after screening

• Pharmacokinetics

• Skin biopsy – lesional

• Blood Biomarkers

• IMP administration and Compliance

• Actigraphy 2






CONFIDENTIAL

End of treatment - Treatment completion/discontinuation Date of last administration of IMP Record date of last administration of IMP using the format day-month-year.

Time of last administration of IMP Record time of last administration of IMP using the 24-hour clock

Has the subject completed the treatment period? Select Yes, if the subject did not permanently discontinue IMP prior to Week 16 visit. If the subject did permanently discontinue IMP prior to Week 16, select No and answer questions below. If No, was the reason for not completing the treatment period related to COVID-19? Select either Yes or No. If No, Primary reason for permanent discontinuation from IMP? Record the reason for permanent discontinuation.

• Death

• Pregnancy

• Adverse event

• Lost to follow-up

• Lack of efficacy

• Withdrawal by subject

• Other

If Lack of efficacy, Specify lack of efficacy




• Other If Other, Specify Specify lack of efficacy, that is not covered by the above.

If Adverse Event, Please complete AE form and specify AE number(s) If Other, Specify Specify primary reason for permanent discontinuation from IMP , that is not covered by the above.

NOTE: If the treatment is stopped prior to Week 16 an early termination visit must be performed. Please complete the Visit Early IMP Termination.






CONFIDENTIAL

End of trial - Trial completion/discontinuation At their last visit in the trial, an end-of-trial form must be completed in the eCRF for all randomized subjects.

NOTE: A subject stopping IMP prematurely is encouraged to stay in the trial without getting more IMP. The "end of trial" form is only to be filled in when the entire trial is stopped, which may be after the IMP is stopped.

Did the subject complete the trial? A subject is considered to have completed the trial if having concluded all periods of the trial including the safety-follow-up visit, regardless of early IMP discontinuation or not. If No, was the reason for not completing the trial due to COVID-19? Select either Yes or No. Date of last contact Record the end of study date as defined in the protocol using the format day-month-year. If No, primary reason for withdrawal from trial Only to be filled out if the subject did not complete the trial. If this is not applicable all related questions should be left blank. NOTE: Options 'Withdrawal by subject' and 'Other' only to be selected if none of the other options are applicable. Select one primary reason withdrawal from trial

• Death: see section ‘Adverse Event’ If the subject died, the adverse event(s) causing the death must also be recorded on the adverse event page(s) (with serious: ‘yes’, ‘Death’: ticked and outcome: ‘fatal’). The completed SAE form must be faxed or scanned and e-mailed to Global Pharmacovigilance at LEO:

E-mail address: [email protected] Fax number: +45 7226 3287

• Pregnancy

• Adverse Event: If the subject does not complete the trial because of an adverse event based on Investigator decision, the corresponding adverse event must be recorded on the adverse events page(s) and ‘Withdrawn from trial due to this AE?’ should be ‘Yes’ on the Adverse Event form. NOTE: The AE must first be entered on the AE form before it can be selected from the search list below.

mailto:[email protected]






CONFIDENTIAL

End of trial - Trial completion/discontinuation - continued

• Lost To follow-up: A subject will be considered lost to follow-up if he/she repeatedly fails to return for scheduled visits and if the trial site is not able to get in contact with the subject. NOTE: Sites are encouraged to attempt to contact the subject 3 times before the subject is considered 'lost to follow-up'.


• Withdrawal by subject: The subject may decide to withdraw from the trial (i.e. stop all further protocol-defined trial activities)

NOTE: Should only be ticked if none of the listed reasons applies.

• Other: NOTE: Should only be ticked, if none of the listed reasons applies and the reason should be specified in If Other, specify field.

If Lack of Efficacy, Specify lack of efficacy




• Other If Other, Specify Specify lack of efficacy, that is not covered by the above.

If Withdrawal by subject did the subject withdraw the informed consent? Select either Yes or No. If Yes, date of withdrawal of the informed consent Provide date subject withdrew consent. If Adverse Event, please complete AE form and specify AE number(s) If Other, Specify If Other is ticked for primary reason, please specify here.






CONFIDENTIAL

End of trial - Trial completion/discontinuation - continued

If No, Did the subject attend the primary endpoint visit?

Only to be filled out if the subject did not complete the trial. If this is not applicable all related questions should be left blank. Tick Yes or No If No, Primary reason for not attending the primary endpoint visit

Record the reason for permanent discontinuation.

• Death

• Pregnancy

• Adverse event




• Other If Adverse Event, please complete AE form and specify AE number(s) If Other, Specify Specify primary reason for not attending the primary endpoint visit, that is not covered by the above.

If No, did the subject attend the safety follow-up visit?

Only to be filled out if the subject did not complete the trial. If this is not applicable all related questions should be left blank. Select either Yes or No. If No, primary reason for not attending safety follow-up visit Record the reason for not attending safety follow-up visit.

• Death

• Pregnancy

• Adverse event




• Other NOTE: Options 'Withdrawal by subject' and 'Other' only to be selected if none of the other options are applicable. If Adverse Event, please complete AE form and specify AE number(s) If Other, Specify Specify primary reason for not attending the safety follow-up visit.






CONFIDENTIAL

Screen failure

Date of screen failure This date is transferred from the IRT system and cannot be entered into the eCRF. Reason for screen failure Select one reason

• Failure to meet eligibility criteria



• Other If Other, specify other reason for screen failure






CONFIDENTIAL

Comments log This page is meant to collect any information that the site believes is useful to complement the data recorded in the eCRF. The Comments should be reviewed by the CRAs and Clinical Data Management before manual queries are considered to be raised. When entering a comment please select the visit and the eCRF page the comment relates to from the drop-down lists. In the comment field itself include the data point the comment relates to including any other identifiers such as a log line number, where applicable. If more than one comment is to be added, click the ‘Complete View’ link and add a new log line for the next comment. Visit number Select the visit to which the comment refers from the drop-down list. NOTE: In the eCRF terminology the term ‘visit’ does not only refer to a subject visit but also a CRF section, e.g. AE/CM/CP events (i.e. visit-independent CRF sections). eCRF Page Select the name of the eCRF page to which your comment refers from the drop-down list. Comment Enter the comment (the comment may consist of up to 200 characters).

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