Study to Compare Tenofovir Alafenamide (TAF) Versus Tenofovir Disoproxil Fumarate (TDF) in Participants With Chronic Hepatitis B Infection Who Are Negative for Hepatitis B e Antigen

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.

Detailed Description
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Study GS-US-320-0108 is a multi-center clinical trial, planned to enroll participants in multiple countries, including China. However, due to the review timeline difference in China, full enrollment was reached in the main study before China was able to participate. Therefore, details for the China cohort was registered separately (NCT02836236) on ClinicalTrials.gov as the China cohort will not be part of 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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HBeAg-negative Chronic Hepatitis B

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 Baseline. Adequate renal function. Normal electrocardiogram (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, human immunodeficiency 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 25 mg<br>TAF + TDF placebo for 96 weeks (per amendment 1 & 2) or 144 weeks (per amendment 3). | Drug: TAF<br>* 25 mg tablet administered orally once daily<br>* Other names: GS-7340;Drug: TDF Placebo<br>* Tablet administered orally once daily<br>|
| Active Comparator: TDF 300 mg<br>TDF + TAF placebo for 96 weeks (per amendment 1 & 2) or 144 weeks (per amendment 3). | Drug: TDF<br>* 300 mg tablet administered orally once daily<br>* Other names: Viread®;Drug: TAF Placebo<br>* Tablet administered orally once daily<br>|
| Experimental: Open-label TAF<br>All participants who complete the double-blind period (96 weeks or 144 weeks) will be eligible to receive open-label TAF until Week 384 of the study. After the end of study treatment, participants can either switch to commercially available anti-HBV treatments in their country or will be followed every 4 weeks, for up to 24 weeks off treatment (treatment-free follow-up (TFFU)) for safety assessment. | Drug: TAF<br>* 25 mg tablet administered orally once daily<br>* Other names: GS-7340;|

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 | The primary efficacy endpoint was determined by the achievement of 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