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

Phase 3
Completed
Conditions
HBV
Chronic HBV Infection
Interventions
Drug: TAF Placebo
Drug: TDF Placebo
Registration Number
NCT02836249
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)-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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
181
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

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 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).
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).
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
Percentage of Participants With Hepatitis B e Antigen (HBeAg) Seroconversion to Antibody Against Hepatitis B e Antigen (Anti-HBe) at Week 48Week 48
Change From Baseline at Week 48 in Serum CreatinineBaseline; Week 48

Trial Locations

Locations (25)

Beijing Ditan Hospital

🇨🇳

Beijing, China

PLA 302 Hospital

🇨🇳

Beijing, China

Beijing Friendship Hospital, Capital Medical University

🇨🇳

Beijing, China

Beijing Youan Hospital, Capital Medical University

🇨🇳

Beijing, China

Xianya Hospital, Central South University

🇨🇳

Changsha, China

Guangzhou Eighth People's Hospital

🇨🇳

Guangzhou, China

Nanfang Medical University, Nanfang Hospital

🇨🇳

Guangzhou, China

No. 3 Hospital, Zhongshan Medical University

🇨🇳

Guangzhou, China

The Affiliated Hospital of Guiyang Medical College

🇨🇳

Guiyang, China

The People's Hospital of Hainan Province

🇨🇳

Haikou, China

The Second Xiangya Hospital of Central South University

🇨🇳

Hunan, China

The First Affiliated Hospital of Nanchang University

🇨🇳

Jiangxi, China

1st Hospital Jilin University

🇨🇳

Jilin, China

Jinan Infectious Disease Hospital

🇨🇳

Jinan, China

Jiangsu Province People's Hospital

🇨🇳

Nanjing, China

2nd Hospital of Nanjing City

🇨🇳

Nanjing, China

Ruijin Hospital, JiaoTong University School of Medicine

🇨🇳

Shanghai, China

Shanghai Public Health Clinical Center

🇨🇳

Shanghai, China

85 Hospital of People's Liberation Army

🇨🇳

Shanghai, China

Shengjing Hospital of China Medical University

🇨🇳

Shenyang, China

The Sixth People's Hospital of Shenyang

🇨🇳

Shenyang, China

3rd Hospital of Hebei Medical University

🇨🇳

Shijiazhuang, China

West China Hospital, Sichuan University

🇨🇳

Sichuan, China

First Affiliated Hospital of Xi'an Jiaotong University

🇨🇳

Xi'an, China

1st Affiliated Hospital Kunming Medical College

🇨🇳

Yunnan, China

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