Targeted Lung Denervation (TLD) in moderate to severe COPD Patients

Arschang Valipour, MD (Study Principal Investigator)Department of Respiratory and Critical Care MedicineO7o-Wagner-Spital, Vienna, Austria06 Sept 2016

IPS-I/II, AIRFLOW-1, and AIRFLOW-2 Trials

• Safety • Feasibility • Dose Ranging

IPS-I / IPS-II

Optimization

• Safety • Efficacy

Pivotal

Feasibility

Key Areas to Optimize •  Dose •  Procedure •  Protocol

TLD COPD Research Program

Generation 1 Device

Generation 2 Device

Overview IPS StudiesSummary IPS-I (NCT# 01483534) IPS-II (NCT# 01716598)

DesignMulticenter study with

staged treatment of right & left lungs

Multicenter study with bilateral treatment of

right & left lungs

ObjectiveAssess safety and

feasibility of TLD over 2 procedures

Assess safety and feasibility of TLD during

1 procedure

Endpoints•  Technical feasibility•  Freedom from worsening of COPD•  Physiological changes (PFT, exercise, QOL)

Patient #n=22

(12 at 20 waYs; 10 at 15 waYs)

n=15 (15 at 15 waYs)

Follow-upDays: 3 and 10

Months: 1, 3, 6 and 9Years: 1, 2 and 3

Available Subjects Over Time (re-consented for longer term follow-up at 1-year, if willing)

IPS-I (n=22)

20

19

15

IPS-II (n=15)

15

10

9

1 Year

2 Years

3 Years

16

1

6

8

4

1

6

1

6MONTHS 1YEAR 2YEARS 3YEARS

ALL

IPS-I IPS-II

IPS-I/II Serious Adverse Events Through 3 Years*

*IPS-I required 2 bronchoscopies 30 days apart

No long-term airway effects reported

-COPD Exac.x3 -gastroenteritis -pancreatic cancer -Pneumonia

-COPD Exac.x3 -hemoptysis -motorcycle accident -stroke

-COPD Exac. x6 -COPD death -pancreatic death

-stroke 11

1

4

7

1 1

3

0

6MONTHS 1YEAR 2YEARS 3YEARS

RESPIRATORYRELATED

IPS-I IPS-II

IPS-I Long-term Airway Safety

90 Day

1 Year

Baseline

IPS-I: Efficacy is Dose Dependent*

*Slebos, et. al., Thorax May 2015

Stronger benefit seen at higher dose

IPS-I: Potential Additive Effect*

*Koegelenberg et al., Respiration June 2016

TLD + drug may exceed any other bronchodilator combination therapy

IPS Conclusions

•  Long-term safety established with no negative airway effects reported out to 3 years.

•  Clear trend toward beYer efficacy at higher dose•  Efficacy demonstrated by:–  TLD alone–  TLD + drug–  Efficacy sustained over time with TLD

Dose and procedural optimization study with generation 2 system

(NCT#02058459)

AIRFLOW-1 Study Overview Energy Level

GroupN=30

3 month optimal power selection based on safety and

efficacyanalysis

ConfirmationGroupN=16

DesignMulticenter, randomized

study assessing two energy levels

Multicenter registry assessing optimal energy

level with procedural enhancements

Objective Assess safety and establish optimal energy level

Assess safety and impact of procedural enhancements

at optimal dose

Primary Endpoint

Rate of airway effects requiring intervention

through 3 months(3 month airway inspection)

Rate and frequency of AEs at

1 month compared to Randomized group.

Energy Level(s)

Low (29 WaYs) and

High (32 WaYs)High (32 WaYs)

AIRFLOW-1 Collaborating Sites AustriaOYo Wagner Spital, Vienna. A. Valipour AKH Allgemeines Krankenhaus, Linz. B. Lamprech

BelgiumAZ Leuven, Leuven. W. Janssens CHU Saint Pierre, Brussels. V. Ninane

FranceCHU de Grenoble. C. Pison CHU de Lille. T. Perez

CHU de Reims. G. Deslee CHU de Strasbourg. R. Kessler

CHU de Paris. A. Marceau

GermanyCharite-Universitatsmedizin, Berlin. R. Hübner Asklepios-Fachkliniken, Gauting. W. Gesierich

Thoraxklinik, Heidelberg. F. Herth

NetherlandsUniversity Medical Centre Groningen. D. Slebos

United KingdomRoyal Brompton, London. P. Shah

AIRFLOW-1 Key Inclusion/ExclusionInclusion:!  FEV1 30% to 60% !  FEV1/FVC <70%!  mMRC grade ≥2 or CAT score ≥10 !  Relative change in FEV1 and/or FVC of >12% and 200 mL during

ipratropium reversibility testing!  Non smoking ≥4 months

Exclusion:•  <6 weeks since COPD exacerbation or active respiratory infection •  PaO2 ≤ 7.3 kPa (55 mm Hg) or PaCO2 > 8.0 kPa (60 mm Hg)•  Pulmonary nodule requiring surgery, radiation and or/chemotherapy•  Previous abdominal surgical procedures•  Elevated baseline gastric questionnaire score

AIRFLOW-1 Conclusions

•  AIRFLOW-1 confirms and builds on IPS studies•  Advancements in procedural technique significantly

improved safety profile–  Enhanced airway protection–  Esophageal management

•  Multiple efficacy measures suggest effect of TLD with

generation 2 system•  Early evidence of both sustained benefit of TLD alone and

additive effect of TLD + drug•  Confirmation Group data available in 2017

First randomized sham control study for TLD

(NCT#02058459)

AIRFLOW-2 Study Overview

Design Multicenter, randomized sham-controlled study

Objective Assess safety and feasibility outcomes between TLD vs. sham-control

Primary Endpoint Rate of respiratory related adverse events between 3 and 6.5 months

Patient # n=80 (1:1 randomization)

Follow-upWeeks: 1

Months: 1, 3, 6*, 9 Years: 1*, 1.5, 2, 2.5, 3

Status Enrolling

*on and off drug assessment time-point

AIRFLOW-2 Key Inclusion/ExclusionMajor Inclusion:!  FEV1 30% to 60% !  FEV1/FVC <70%!  mMRC grade ≥2 or CAT score ≥10 !  Non smoking ≥2 months

Major Exclusion:•  <6 weeks since COPD exacerbation or active respiratory infection •  PaO2 ≤ 7.3 kPa (55 mm Hg) or PaCO2 > 8.0 kPa (60 mm Hg)•  Pulmonary nodule requiring surgery, radiation and or/chemotherapy•  Elevated baseline gastric questionnaire score

AIRFLOW-2 Inflammatory Sub-study

•  Goal: understand anti-inflammatory effects of TLD–  40 subject to participate (20 test, 20 sham)–  Expand on results from earlier IPS-I Study

Kistemaker et al., Eur Respir J (2015)

AIRFLOW-2 Collaborating Sites Austria

OYo Wagner Spital, Vienna. A. Valipour AKH Allgemeines Krankenhaus, Linz. B. Lamprech

France

CHU de Grenoble. C. Pison CHU de Lille. T. Perez

CHU de Reims. G. Deslee CHU de Strasbourg. R. Kessler

CHU de Paris. A. Marceau

Germany

Charite-Universitatsmedizin, Berlin. R. Hübner Asklepios-Fachkliniken, Gauting. W. Gesierich

Thoraxklinik, Heidelberg. F. Herth Ruhrlandklinik, Essen. K. Darwiche

Klinikverbund, Kempten. C. Schumann

Netherlands

University Medical Centre Groningen. D. Slebos Academisch Medisch Centrum. P. Bonta

United Kingdom

Royal Brompton, London. P. Shah Queen Elizabeth University Hospital, Glasgow S. Bicknell

www.airflowtrial.com

Thank you