Efficacy and Safety of Tenofovir Disoproxil Fumarate (TDF) 300mg in Chinese Subjects With Chronic Hepatitis B (CHB)

NCT ID: NCT01300234

Last Updated: 2018-07-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 512 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-03-30
• Study Completion Date: 2016-12-06

Brief Summary

This is a multi-centre, double blind, double dummy, randomised, controlled study to evaluate the efficacy and safety of TDF 300mg QD versus ADV 10mg QD in Chinese subjects with CHB. This study is designed to demonstrate the superiority of TDF 300mg QD over ADV 10mg QD in treating Chinese subjects with CHB (hepatitis B e antigen [HBeAg] positive subjects and HBeAg negative subjects). It will also provide long-term efficacy and safety data (up to 240 weeks) for TDF 300 mg administered once daily.

Detailed Description

This is a multi-centre, double-blind, double-dummy, randomised, controlled study to evaluate the efficacy and safety of TDF 300mg QD versus ADV 10mg QD in Chinese subjects with CHB. Four hundred and ninety-four subjects with CHB (200 HBeAg positive subjects and 294 HBeAg negative subjects) will be randomised (1:1ratio) to either TDF 300mg QD or ADV 10mg QD treatment arms. The primary endpoint is the proportion of subjects with blood hepatitis B virus (HBV) deoxyribonucleic acid (DNA) <400copies/mL (Roche COBAS Taqman HBV test) at Week 48 in HBeAg positive subjects with CHB and HBeAg negative subjects with CHB. This is a two-part study. The first treatment period (baseline to Week 48) will investigate the effects of TDF and ADV on safety and efficacy endpoints; dosing will be double-blind. This period will be followed by 192 weeks in which all subjects will receive open-label TDF (Week 49 to Week 240). Subjects will undergo regular safety and efficacy assessments every 4 weeks for the first 12 weeks followed by every 12 weeks for a total of up to 5 years.

Conditions

Hepatitis B

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

A (TDF tablets)

Tenofovir disoproxil fumarate (TDF) tablets

Group Type: EXPERIMENTAL

Tenofovir disoproxil fumarate (TDF) tablets

Intervention Type: DRUG

white, almond-shaped, film-coated tablets containing 300mg of TDF

B (ADV tablets)

Adefovir dipivoxil (ADV) tablets

Group Type: ACTIVE_COMPARATOR

Adefovir dipivoxil (ADV) tablets

Intervention Type: DRUG

white to off-white, round, biconvex tablets containing 10mg of ADV

Interventions

Tenofovir disoproxil fumarate (TDF) tablets

white, almond-shaped, film-coated tablets containing 300mg of TDF

Intervention Type: DRUG

Adefovir dipivoxil (ADV) tablets

white to off-white, round, biconvex tablets containing 10mg of ADV

Intervention Type: DRUG

Other Intervention Names

TDF tablet; ADV tablet

Eligibility Criteria

Inclusion Criteria

• HBeAg positive/negative CHB with blood HBVDNA≥10^5 copies/mL and elevated ALT
• Nucleoside and nucleotide naïve CHB subjects. Previous lamivudine treatment is allowed in less than 10% of the total study population

Exclusion Criteria

• subjects with hepatocellular carcinoma (HCC) potential or decompensated liver disease
• subjects with acute liver disease due to other causes
• subjects with medication history of immunosuppressive therapy, immunomodulatory therapy, systemic cytotoxic agents, chronic antiviral agents including Chinese herbal medicines known to have activity against HBV (e.g., lamivudine, hepatitis B immunoglobulin (HBIg)) within the previous 6 months prior to randomisation into this study

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 69 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Guangzhou, Guangdong, China

GSK Investigational Site

Guangzhou, Guangdong, China

GSK Investigational Site

Guangzhou, Guangdong, China

GSK Investigational Site

Wuhan, Hubei, China

GSK Investigational Site

Changsha, Hunan, China

GSK Investigational Site

Nanjing, Jiangsu, China

GSK Investigational Site

Nanjing, Jiangsu, China

GSK Investigational Site

Changchun, Jilin, China

GSK Investigational Site

Chengdu, Sichuan, China

GSK Investigational Site

Hangzhou, Zhejiang, China

GSK Investigational Site

Beijing, , China

GSK Investigational Site

Beijing, , China

GSK Investigational Site

Beijing, , China

GSK Investigational Site

Chongqing, , China

GSK Investigational Site

Fuzhou, , China

GSK Investigational Site

Jinan, , China

GSK Investigational Site

Shanghai, , China

GSK Investigational Site

Shanghai, , China

GSK Investigational Site

Shanghai, , China

GSK Investigational Site

Shanghai, , China

Countries

China

References

Liang X, Gao Z, Xie Q, Zhang J, Sheng J, Cheng J, Chen C, Mao Q, Zhao W, Ren H, Tan D, Niu J, Chen S, Pan C, Tang H, Wang H, Mao Y, Jia J, Ning Q, Xu M, Wu S, Li J, Zhang X, Zhang W, Xiong C, Hou J. Long-term efficacy and safety of tenofovir disoproxil fumarate in Chinese patients with chronic hepatitis B: 5-year results. Hepatol Int. 2019 May;13(3):260-269. doi: 10.1007/s12072-019-09943-6. Epub 2019 Apr 11.

Reference Type: DERIVED

PMID: 30977033 (View on PubMed)

Hou JL, Gao ZL, Xie Q, Zhang JM, Sheng JF, Cheng J, Chen CW, Mao Q, Zhao W, Ren H, Tan DM, Niu JQ, Chen SJ, Pan C, Tang H, Wang H, Mao YM, Jia JD, Ning Q, Xu M, Wu SM, Li J, Zhang XX, Ji Y, Dong J, Li J. Tenofovir disoproxil fumarate vs adefovir dipivoxil in Chinese patients with chronic hepatitis B after 48 weeks: a randomized controlled trial. J Viral Hepat. 2015 Feb;22(2):85-93. doi: 10.1111/jvh.12313. Epub 2014 Sep 22.

Reference Type: DERIVED

PMID: 25243325 (View on PubMed)

Other Identifiers

114648

Identifier Type: -

Identifier Source: org_study_id