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

NCT01300234 | Completed Phase 3 Results

• 1 other identifier: 114648
• Study Type: interventional
• Target: 512
• Locations: 1 country
• Sites: 20

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.

Conditions

Hepatitis B

Keywords

tenofovir disoproxil fumarate; chronic hepatitis B; adefovir dipivoxil

Outcome Measures

Primary Outcomes (1)

• Participants With Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) <400 Copies/Milliliter (mL) at Week 48

  The number of participants with Hepatitis B Virus (HBV) deoxyribonucleic acid (DNA) \<400 copies/milliliter (mL) at Week 48 in the hepatitis B e antigen (HBeAg)-positive and HBeAg-negative population was assessed. HBeAg is a viral protein that is secreted by hepatitis B-infected cells. It is associated with chronic hepatitis B infections and is used as a marker of active viral disease and a participant's degree of infectiousness. A positive result indicates that the participant has high levels of virus in the blood and greater infectiousness. Usually, a negative result indicates that the participant has lower levels of virus in the blood and is less infectious. A "non-completers equal failures" approach is used for the analysis in ITT population. Only those participants available at the specified time points (represented by n=X in the category titles) were analyzed.

  Week 48

Secondary Outcomes (14)

• Participants With HBV DNA <400 Copies/mL at Weeks 96, 144, 192, and 240

  Weeks 96, 144, 192, and 240

• Change From Baseline of Log 10 Copies/mL HBV DNA at Weeks 48, 96, 144, 192 and 240

  Baseline, Weeks 48, 96, 144, 192 and 240

• Number of Participants With Alanine Aminotransferase (ALT) Normalization at Weeks 48, 96, 144, 192 and 240 in Participants Who Had Abnormal ALT at Baseline

  Baseline; Weeks 48, 96, 144, 192 and 240

• Number of Participants With Histological Improvement at Weeks 48 and 240 Who Had a Baseline Knodell Necroinflammatory Score (KNS) >=2.

  Baseline; Week 48 and Week 240

• Number of HBeAg-positive Participants Achieving HBeAg Loss and HBeAg Seroconversion at Weeks 24, 48, 96, 144, 192 and 240.

  Weeks 24, 48, 96, 144, 192 and 240

Study Arms (2)

A (TDF tablets)

EXPERIMENTAL

Tenofovir disoproxil fumarate (TDF) tablets

Drug: Tenofovir disoproxil fumarate (TDF) tablets

B (ADV tablets)

ACTIVE COMPARATOR

Adefovir dipivoxil (ADV) tablets

Drug: Adefovir dipivoxil (ADV) tablets

Interventions

Tenofovir disoproxil fumarate (TDF) tablets DRUG

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

Also known as: TDF tablet

A (TDF tablets)

Adefovir dipivoxil (ADV) tablets DRUG

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

Also known as: ADV tablet

B (ADV tablets)

Eligibility Criteria

• Age: 18 Years - 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (20)

GSK Investigational Site

Guangzhou, Guangdong, 510060, China

Location

GSK Investigational Site

Guangzhou, Guangdong, 510515, China

Location

GSK Investigational Site

Guangzhou, Guangdong, 510630, China

Location

GSK Investigational Site

Wuhan, Hubei, 430030, China

Location

GSK Investigational Site

Changsha, Hunan, 410008, China

Location

GSK Investigational Site

Nanjing, Jiangsu, 210003, China

Location

GSK Investigational Site

Nanjing, Jiangsu, 210029, China

Location

GSK Investigational Site

Changchun, Jilin, 130021, China

Location

GSK Investigational Site

Chengdu, Sichuan, 610041, China

Location

GSK Investigational Site

Hangzhou, Zhejiang, 310003, China

Location

GSK Investigational Site

Beijing, 100015, China

Location

GSK Investigational Site

Beijing, 100044, China

Location

GSK Investigational Site

Beijing, 100050, China

Location

GSK Investigational Site

Chongqing, 400038, China

Location

GSK Investigational Site

Fuzhou, 350025, China

Location

GSK Investigational Site

Jinan, 250021, China

Location

GSK Investigational Site

Shanghai, 200001, China

Location

GSK Investigational Site

Shanghai, 200025, China

Location

GSK Investigational Site

Shanghai, 200040, China

Location

GSK Investigational Site

Shanghai, 201508, China

Location

Related Publications (2)

• 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.

  PMID: 30977033 DERIVED

• 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.

  PMID: 25243325 DERIVED

MeSH Terms

Conditions

Hepatitis B; Hepatitis B, Chronic

Interventions

Tenofovir; Tablets; adefovir dipivoxil

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis; Liver Diseases; Digestive System Diseases; Hepatitis, Chronic; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Dosage Forms; Pharmaceutical Preparations

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 3, 2011
• First Posted: February 21, 2011
• Study Start: March 30, 2011
• Primary Completion: October 17, 2012
• Study Completion: December 6, 2016
• Last Updated: July 13, 2018
• Results First Posted: August 16, 2013

Record last verified: 2018-01

Locations

CN (20)