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 Positive, Chronic Hepatitis B
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Gilead Sciences
- Enrollment
- 181
- Locations
- 25
- Primary Endpoint
- Percentage of Participants With Hepatitis B Virus (HBV) DNA < 29 IU/mL at Week 48
Study Overview
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 in China.
Detailed Description
This study GS-US-320-0110 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 (NCT01940471) 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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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 ECG
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.
Arms & Interventions
Double-Blind TAF
Tenofovir alafenamide (Vemlidy®; TAF) 25 mg tablet + tenofovir disoproxil fumarate (Viread®; TDF) placebo tablet once daily for up to 144 weeks (per amendment 3.1).
Intervention: TAF (Drug)
Double-Blind TAF
Tenofovir alafenamide (Vemlidy®; TAF) 25 mg tablet + tenofovir disoproxil fumarate (Viread®; TDF) placebo tablet once daily for up to 144 weeks (per amendment 3.1).
Intervention: TDF Placebo (Drug)
Double-Blind TDF
TDF 300 mg tablet + TAF placebo tablet once daily for up to 144 weeks (per amendment 3.1).
Intervention: TDF (Drug)
Double-Blind TDF
TDF 300 mg tablet + TAF placebo tablet once daily for up to 144 weeks (per amendment 3.1).
Intervention: TAF Placebo (Drug)
Open-label TAF
All participants who complete the double-blind period will be eligible to receive open-label TAF until Week 384 of the study.
Intervention: TAF (Drug)
Outcomes
Primary Outcomes
Percentage of Participants With Hepatitis B Virus (HBV) DNA < 29 IU/mL at Week 48
Time Frame: Week 48
Secondary Outcomes
- 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)
- Percentage of Participants With Hepatitis B e Antigen (HBeAg) Seroconversion to Antibody Against Hepatitis B e Antigen (Anti-HBe) at Week 48(Week 48)
- Change From Baseline at Week 48 in Serum Creatinine(Baseline; Week 48)