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

Phase 3
Completed
Conditions
HBV
Chronic HBV Infection
Interventions
Drug: TDF Placebo
Drug: TAF Placebo
Registration Number
NCT02836236
Lead Sponsor
Gilead Sciences
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

Status
COMPLETED
Sex
All
Target Recruitment
155
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Double-Blind TAFTAFTenofovir 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 TAFTDF PlaceboTenofovir 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 TDFTDFTDF 300 mg tablet + TAF placebo tablet once daily for up to 144 weeks (per amendment 3.1).
Double-Blind TDFTAF PlaceboTDF 300 mg tablet + TAF placebo tablet once daily for up to 144 weeks (per amendment 3.1).
Open-label TAFTAFAll participants who complete the double-blind period will be eligible to receive open-label TAF until Week 384 of the study.
Primary Outcome Measures
NameTimeMethod
Percentage of Participants With Hepatitis B Virus (HBV) DNA < 29 IU/mL at Week 48Week 48
Secondary Outcome Measures
NameTimeMethod
Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48Baseline, Week 48
Percent Change From Baseline in Spine BMD at Week 48Baseline, Week 48
Change From Baseline in Serum Creatinine at Week 48Baseline, Week 48

Trial Locations

Locations (29)

Beijing Ditan Hospital

🇨🇳

Beijing, China

Beijing Friendship Hospital, Capital Medical University

🇨🇳

Beijing, China

Beijing Youan Hospital, Capital Medical University

🇨🇳

Beijing, China

85 Hospital of People's Liberation Army

🇨🇳

Shanghai, China

The First Hospital of Jilin University

🇨🇳

Changchun, Jilin, China

West China Hospital, Sichuan University

🇨🇳

Chengdu, Sichuan, China

The People's Hospital of Hainan Province

🇨🇳

Haikou, China

Nanjing No. 2 Hospital

🇨🇳

Nanjing, Jiangsu, China

The 3rd Hospital of Hebei Medical University

🇨🇳

Shijiazhuang, Hebei, China

Jinan Infectious Disease Hospital

🇨🇳

Jinan, Shandong, China

The Affiliated Hospital of Guiyang Medical College

🇨🇳

Guiyang, Guiyang, China

The Third Affiliated Hospital of Sun Yat-Sen University

🇨🇳

Guangzhou, Guangdong, China

The sixth People's Hospital of Shenyang

🇨🇳

Shenyang, Liaoning, China

Tongji Hospital, Tongji Medical college HuaZhong University of Science&Technology

🇨🇳

Wuhan, Hubei, China

The First Affiliated Hospital of Nanchang University

🇨🇳

Nanchang, Jiangxi, China

No.1 Hospital Affiliated to Kunming Medical College

🇨🇳

Kunming, Yunnan, China

No. 302 PLA Hospital

🇨🇳

Beijing, China

Peking University People's Hospital

🇨🇳

Beijing, China

The 2nd Xiangya Hospital Central South University

🇨🇳

Changsha, China

Nanfang Medical University, Nanfang Hospital

🇨🇳

Guangzhou, China

Jiangsu Provincial People's Hospital

🇨🇳

Nanjing, China

Rui Jin Hospital Shanghai Jiao Tong University School of Medicine

🇨🇳

Shanghai, China

The 1st Affiliated Hospital of Guangxi Medical University

🇨🇳

Nanning, Guangxi, China

XiangYa Hospital Central South University

🇨🇳

Changsha, China

Guangzhou No.8 People's Hospital

🇨🇳

Guangzhou, China

Shanghai Public Health Clinical Center

🇨🇳

Shanghai, China

Shengjing Hospital of China Medical University

🇨🇳

Shenyang, China

First Affiliated Hospital of Xi'an Jiaotong

🇨🇳

Xi'an, China

Peking University First Hospital

🇨🇳

Beijing, Beijing, China

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