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

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)-negative chronic hepatitis B virus (HBV) infection in China.

Detailed Description: 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 was completed.

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
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.

Arm && Interventions

Group	Intervention	Description
Double-Blind TAF	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).
Double-Blind TAF	TDF Placebo	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).
Double-Blind TDF	TDF	TDF 300 mg tablet + TAF placebo tablet once daily for up to 144 weeks (per amendment 3.1).
Double-Blind TDF	TAF Placebo	TDF 300 mg tablet + TAF placebo tablet once daily for up to 144 weeks (per amendment 3.1).
Open-label TAF	TAF	All participants who complete the double-blind period will be eligible to receive open-label TAF until Week 384 of the study.

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
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

Locations (29): Peking University First Hospital
🇨🇳
Beijing, Beijing, China
The Third Affiliated Hospital of Sun Yat-Sen University
🇨🇳
Guangzhou, Guangdong, China
The 1st Affiliated Hospital of Guangxi Medical University
🇨🇳
Nanning, Guangxi, China
The Affiliated Hospital of Guiyang Medical College
🇨🇳
Guiyang, Guiyang, China
The 3rd Hospital of Hebei Medical University
🇨🇳
Shijiazhuang, Hebei, China
Tongji Hospital, Tongji Medical college HuaZhong University of Science&Technology
🇨🇳
Wuhan, Hubei, China
Nanjing No. 2 Hospital
🇨🇳
Nanjing, Jiangsu, China
The First Affiliated Hospital of Nanchang University
🇨🇳
Nanchang, Jiangxi, China
The First Hospital of Jilin University
🇨🇳
Changchun, Jilin, China
The sixth People's Hospital of Shenyang
🇨🇳
Shenyang, Liaoning, China
Scroll for more (19 remaining)
Peking University First Hospital
🇨🇳Beijing, Beijing, China