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

Phase 3

Completed

Brief Summary: 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)-positive chronic hepatitis B virus (HBV) infection.

Detailed Description: This study GS-US-320-0110 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 are registered separately (NCT02836249) on ClinicalTrials.gov as this cohort will not be part of the main study analysis.

Recruitment & Eligibility

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.
HBeAg-positive, chronic hepatitis B with all of the following:
- HBeAg-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 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.

Arm && Interventions

Group	Intervention	Description
TAF 25 mg	TDF Placebo	TAF + TDF placebo for 96 weeks (per amendment 1 \& 2) or 144 weeks (per amendment 3).
TDF 300 mg	TDF	TDF + TAF placebo for 96 weeks (per amendment 1 \& 2) or 144 weeks (per amendment 3).
TDF 300 mg	TAF Placebo	TDF + TAF placebo for 96 weeks (per amendment 1 \& 2) or 144 weeks (per amendment 3).
TAF 25 mg	TAF	TAF + TDF placebo for 96 weeks (per amendment 1 \& 2) or 144 weeks (per amendment 3).
Open-label TAF	TAF	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.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Hepatitis B Virus (HBV) DNA < 29 IU/mL at Week 48	Week 48

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Hepatitis B e Antigen (HBeAg) Seroconversion to Antibody Against Hepatitis B e Antigen (Anti-HBe) at Week 48	Week 48
Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48	Baseline, Week 48
Change From Baseline at Week 48 in Serum Creatinine	Baseline, Week 48
Percent Change From Baseline in Spine BMD at Week 48	Baseline, Week 48

Locations (158): Coalition of Inclusive Medicine
🇺🇸
Los Angeles, California, United States
Stanford University Medical Center
🇺🇸
Palo Alto, California, United States
Huntington Medical Research Institutes
🇺🇸
Pasadena, California, United States
Research and Education, Inc.
🇺🇸
San Diego, California, United States
Silicon Valley Research Institute
🇺🇸
San Jose, California, United States
University of Miami
🇺🇸
Miami, Florida, United States
Digestive Disease Associates, PA
🇺🇸
Catonsville, Maryland, United States
Tufts Medical Center, Inc
🇺🇸
Boston, Massachusetts, United States
Henry Ford Health System
🇺🇸
Detroit, Michigan, United States
Sing Chan Private Practice
🇺🇸
Flushing, New York, United States
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Coalition of Inclusive Medicine
🇺🇸Los Angeles, California, United States