Clinical Trials for CHB in China

Ji-Dong Jia, MD, PhD

Beijing Friendship Hospital

Capital Medical University

May 10, 2013

Introduction of GCP to China

• In 1986, information on international GCP

started to be collected

• In 1993, international were invited to introduce

GCP principles and practices

• In 1994, symposium on GCP were held and

China GCP guideline were proposed

• In 1995，China GCP were drafted by a working

party of 5 experts on clinical pharmacology,

and GCP training courses were held across

China

Development of China GCP

• In 1998, SDA MOH released China GCP

• In 1999, SDA MOH issued China GCP

• In 2003, SFAD updated China GCP

Difference between ICH-GCP and China GCP

China GCP ICH-GCP

Approval for

clinical trials

SFDA approval is required Not required

Institution

accreditation

SFDA accreditation is

required

Not required

PI’s qualification License for clinical practice

is required

Not required

IRB/EC Based in the institution Not required

4

http://www.sfda.gov.cn/WS01/CL0053/24473.html

China GCP-2003

http://www.chictr.org/en/

ChiCTR sponsored by MOH was launched in May 2007

ChiCTR was accepted as the 4th Primary Registry of WHO ITRP In June 2007

Prevalence of HBsAg in China 1979,1992 and 2006

0.00

2.00

4.00

6.00

8.00

10.00

12.001

~4

5~9

10~

14

15~

19

20~

24

25~

29

30~

34

35~

39

40~

44

45~

49

50~

54

55~

49

HB

sAg

(%)

Age Group (year)

1979

1992

2006

1.Qu Z. An epidemiological study on the distribution of HBsAg and anti-HBs in China. Chine Journal of Microbiogy Immunology. 1986; Suppl(20-40).

2.Dai ZC, G.M. Q. Seroepidemiological Survey in Chinese population (part one), 1992–1995. Beijing. Sci Tech Exp. 1996: 39-59.

3.Liang X, Bi S, Yang W, Wang L, Cui G, Cui F, et al. Epidemiological serosurvey of hepatitis B in China--declining HBV prevalence due to hepatitis B vaccination. Vaccine. 2009; 27(47): 6550-7.

1～4 0.96%

5～14 2.42%

15～59 8.57%

Anti-HCV Prevalence in China in 1992 and 2006

1992

2006

4.0

3.5

3.0

2.5

2.0

1.5

1.0

0.5

0.0

0 10 20 30 40 50 60

An

ti-H

CV

(%

)

年龄组(岁)

Chen YS，et al. Chin J Epidemiol 2011;32:888-91

HBV/HCV Clinical Trials from China Registered at www.clinicaltrials.gov

0

10

20

30

40

50

60

HBV HCV

2001-2005

2006-2010

2011-2013

PubMed Indexed English Papers of

RCT on HBV/HCV in China

0

10

20

30

40

50

HBV HCV

1990-1995

1996-2000

2001-2005

2006-2010

2011-2012

RCT papers of hepatitis treatment in China:

the development from 1990 to 2009

36

21

44

72

10

16

10 8

16 15

05

101520253035404550

1990/1-1995/1

1995/2-2000/1

2000/2-2005/1

2005/2-2009/7

ML- China

HK

TW

N Engl J Med 2004;351:1521-31.

(HEPATOLOGY 2006;44:108-116.)

N Engl J Med 2007;357:2576-88.

HEPATOLOGY 2008;47:447-454.

GASTROENTEROLOGY 2009;136:486–495

Phase III trial of PEG-IFN alfa-2a in

HBeAg+ CHB

Peginterferon alfa-2a as monotherapy and in combination with

lamivudine versus lamivudine monotherapy in patients with

HBeAg-positive chronic hepatitis B George K.K. Lau, M.D., Teerha Piratvisuth, M.D., Kang Xian Luo, M.D.,Patrick Marcellin, M.D.,

Satawat Thongsawat, M.D., Graham Cooksley, M.D.,Edward Gane, M.D., Michael W. Fried, M.D.,

Wan Cheng Chow, M.D.,Seung Woon Paik, M.D., Wen Yu Chang, M.D., Thomas Berg, M.D.,

Robert Flisiak, M.D., Philip McCloud, Ph.D., and Nigel Pluck, M.D.,for the Peginterferon Alfa-2a

HBeAg-Positive Chronic Hepatitis B Study Group*

Volume 352 June 30, 2005 Number 26

Volume 351

September 16, 2005

Number 12

Peginterferon Alfa-2a Alone, Lamivudine Alone, and the Two in Combination in Patients with

HBeAg-Negative Chronic Hepatitis B

Patrick Marcellin, M.D., George K.K. Lau, M.D., Ferruccio Bonino, M.D., Patrizia Farci, M.D., Stephanos Hadziyannis,

M.D., Rui Jin, M.D., Zhi-Meng Lu, M.D., Teerha Piratvisuth, M.D., Georgios Germanidis, M.D., Cihan Yurdaydin, M.D.,

Moises Diago, M.D., Selim Gurel, M.D., Ming-Yang Lai, M.D., Peter Button, M.Sc., Nigel Pluck, M.D., for the Peginterferon

Alfa-2a HBeAg-Negative Chronic Hepatitis B Study Group

Phase III trial of PEG-IFN alfa-2a

in HBeAg- CHB

22

Clinical Infectious Diseases 2007;

44:541–8

23

HEPATOLOGY 2011;54:1591-1599

24

25

研究特点 研究内容

• 围绕优化治疗提高疗效的总体目标

• 一组创新性的临床治疗研究方案

• 前瞻、随机、对照的临床研究设计

• 中国特色研究

1.EFFORT--替比夫定优化治疗

2.EXPLORE--拉米夫定优化治疗

3.EXCEL--长效干扰素优化治疗

4.Dragon--核苷类似物治疗应答不佳

（难治性）的优化治疗

课题编号2008ZX10002-004

侯金林 ClinicalTrials.gov

慢性乙型肝炎临床治疗方案的优化 及影响疗效的因素

W52 基线 W24

I-A : Wk 24 PCR+: >300

加用 ADV

W104

LDT

LDT

I-B: Wk 24 PCR - : <300

LdT 单用

病毒突破者加用ADV

I组 302例

II组 302例

45%

55%

W12

26

Acknowledgement