A Multi-centre, Double Blind, Double Dummy, Randomised, Controlled Study to Evaluate the Efficacy and Safety of TDF 300mg Once Daily (QD) Versus Adefovir Dipivoxil (ADV) 10mg QD in Chinese Subjects With CHB
Overview
- Phase
- Phase 3
- Intervention
- Tenofovir disoproxil fumarate (TDF) tablets
- Conditions
- Hepatitis B
- Sponsor
- GlaxoSmithKline
- Enrollment
- 512
- Locations
- 1
- Primary Endpoint
- Participants With Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) <400 Copies/Milliliter (mL) at Week 48
- Status
- Completed
- Last Updated
- 7 years ago
Overview
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.
Investigators
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
Arms & Interventions
A (TDF tablets)
Tenofovir disoproxil fumarate (TDF) tablets
Intervention: Tenofovir disoproxil fumarate (TDF) tablets
B (ADV tablets)
Adefovir dipivoxil (ADV) tablets
Intervention: Adefovir dipivoxil (ADV) tablets
Outcomes
Primary Outcomes
Participants With Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) <400 Copies/Milliliter (mL) at Week 48
Time Frame: 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.
Secondary Outcomes
- 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)
- Number of HBeAg-positive Participants Achieving Hepatitis B Surface Antigen (HBsAg) Loss and HBsAg Seroconversion at Weeks 24, 48, 96, 144, 192 and 240(Weeks 24, 48, 96, 144, 192 and 240)
- Number of HBeAg-negative Participants Achieving HBsAg Loss and HBsAg Seroconversion at Weeks 24, 48, 96, 144, 192, 240(Weeks 24, 48, 96, 144, 192 and 240)
- Number of Participants Achieving Durable HBsAg Loss From Weeks 24 to Week 48(Week 24 to Week 48)
- Number of Participants Achieving Durable HBsAg Loss From Weeks 96 to Week 240(Week 96 to Week 240)
- Number of Participants With Virological Breakthrough at Weeks 48, 96, 144, 192 and 240(Weeks 48, 96, 144, 192 and 240)
- Number of Participants With Any Serious Adverse Event (SAE) and Any Non-serious Adverse Event (AE)(Up to Week 240 treatment period and 24 weeks follow-up visit off treatment)
- Number of Participants With the Indicated Grade 3 and Grade 4 Treatment-emergent (TE) Laboratory Abnormalities (LAs)(Up to Week 240)
- Number of Participants With the Indicated Treatment-emergent Laboratory Abnormalities for Serum Creatinine and Serum Phosphorus(Up to Week 240)
- Number of Participants in the Indicated Category for Renal Laboratory Abnormalities(Up to Week 240)