Tenofovir Alafenamide Versus Tenofovir Disoproxil Fumarate for Treatment of Hepatitis B e Antigen-Negative Hepatitis B (China)

Study Overview
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Brief Summary
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The primary objective of this study is to compare the efficacy, safety, and tolerability of tenofovir alafenamide (TAF) versus tenofovir disoproxil fumarate (TDF) in treatment-naive and treatment-experienced adults with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B virus (HBV) infection in China.

Detailed Description
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This study GS-US-320-0108 is an international study planned to enroll participants in global countries, including China. However, due to the review timeline difference in China, full enrollment was reached in the main study (NCT01940341) before China was able to participate. Therefore, this registration only includes the China cohorts as they were not part of the main study analysis. Data for China cohorts were analyzed separately after the main study analysis.

Official Title
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A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of Tenofovir Alafenamide (TAF) 25 mg QD Versus Tenofovir Disoproxil Fumarate (TDF) 300 mg QD for the Treatment of HBeAg-Negative, Chronic Hepatitis B

Conditions
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HBV, Chronic HBV Infections

Intervention / Treatment
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* Drug: TAF
* Drug: TDF
* Drug: TAF Placebo
* Drug: TDF Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures Adult males and non-pregnant, non-lactating females Documented evidence of chronic HBV infection Hepatitis e antigen (HBeAg)-negative, chronic hepatitis B with all of the following: HBeAg-negative and hepatitis B e antibody (HBeAb) positive at screening Screening HBV DNA ≥ 2 x 10^4 IU/mL Screening serum alanine aminotransferase (ALT) level > 60 U/L (males) or > 38 U/L (females) and ≤ 10 x the upper limit of the normal range (ULN) Treatment-naive participants (defined as < 12 weeks of oral antiviral treatment with any nucleoside or nucleotide analogue), OR treatment-experienced participants (defined as participants meeting all entry criteria [including HBV DNA and serum ALT criteria] and with ≥ 12 weeks of previous treatment with any nucleoside or nucleotide analogue) Previous treatment with interferon (pegylated or non-pegylated) must have ended at least 6 months prior to the baseline visit. Adequate renal function Normal ECG Key Exclusion Criteria: Females who are breastfeeding Males and females of reproductive potential who are unwilling to use an effective, protocol-specified method(s) of contraception during the study Co-infection with hepatitis C virus, HIV, or hepatitis D virus Evidence of hepatocellular carcinoma Any history of, or current evidence of, clinical hepatic decompensation Abnormal hematological and biochemical parameters, including aspartate aminotransferase (AST) > 10 x ULN Received solid organ or bone marrow transplant History of malignancy within the past 5 years, with the exception of specific cancers that are cured by surgical resection; individuals under evaluation for possible malignancy are not eligible Currently receiving therapy with immunomodulators (eg, corticosteroids), investigational agents, nephrotoxic agents, or agents capable of modifying renal excretion Individuals receiving ongoing therapy with drugs not to be used with tenofovir alafenamide or tenofovir disoproxil fumarate or individuals with a known hypersensitivity to study drugs, metabolites, or formulation excipients Current alcohol or substance abuse judged by the investigator to potentially interfere with participant compliance Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the participant unsuitable for the study or unable to comply with dosing requirements Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TAF<br>TAF + TDF placebo for up to 144 weeks | Drug: TAF<br>* TAF 25 mg tablet administered orally once daily<br>* Other names: Vemlidy®;Drug: TDF Placebo<br>* TDF placebo tablet administered orally once daily<br>|
| Active Comparator: TDF<br>TDF + TAF placebo for up to 144 weeks | Drug: TDF<br>* TDF 300 mg tablet administered orally once daily<br>* Other names: Viread®;Drug: TAF Placebo<br>* TAF placebo tablet administered orally once daily<br>|
| Experimental: Open-label TAF<br>All participants who complete the double-blind period will be eligible to receive open-label TAF until Week 384 of the study. | Drug: TAF<br>* TAF 25 mg tablet administered orally once daily<br>* Other names: Vemlidy®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Hepatitis B Virus (HBV) DNA < 29 IU/mL at Week 48 |  | Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48 |  | Baseline; Week 48 | 
| Percent Change From Baseline in Spine BMD at Week 48 |  | Baseline; Week 48 | 
| Change From Baseline in Serum Creatinine at Week 48 |  | Baseline; Week 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatitis, Tenofovir, Viread