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

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-Negative, Chronic Hepatitis B

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.

Study Overview

• Status: Completed
• Conditions: HBV; Chronic HBV Infections
• Intervention / Treatment: Drug: TAF; Drug: TDF Placebo; Drug: TDF; Drug: TAF Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 155
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100044
    • Peking University People's Hospital
  • Beijing, China, 100069
    • Beijing Youan Hospital, Capital Medical University
  • Beijing, China, 100050
    • Beijing Friendship Hospital, Capital Medical University
  • Beijing, China, 100015
    • Beijing Ditan Hospital
  • Beijing, China, 100039
    • No. 302 PLA Hospital
  • Changsha, China, 410008
    • Xiangya Hospital Central South University
  • Changsha, China, 410011
    • The 2nd Xiangya Hospital Central South University
  • Guangzhou, China, 510515
    • Nanfang Medical University, Nanfang Hospital
  • Guangzhou, China, 510060
    • Guangzhou No.8 People's Hospital
  • Haikou, China, 570311
    • The People's Hospital of Hainan Province
  • Nanjing, China, 210029
    • Jiangsu Provincial People's Hospital
  • Shanghai, China, 200083
    • Shanghai Public Health Clinical Center
  • Shanghai, China, 200235
    • 85 Hospital of People's Liberation Army
  • Shanghai, China, 200025
    • Rui Jin Hospital Shanghai Jiao Tong University School of Medicine
  • Shenyang, China, 110004
    • Shengjing Hospital of China Medical University
  • Xi'an, China, 710061
    • First Affiliated Hospital of Xi'an Jiaotong
  • Beijing
    • Beijing, Beijing, China, 100034
      • Peking University First Hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 510630
      • The Third Affiliated Hospital of Sun Yat-sen University
  • Guangxi
    • Nanning, Guangxi, China, 530021
      • The 1st Affiliated Hospital of Guangxi Medical University
  • Guiyang
    • Guiyang, Guiyang, China, 550004
      • The affiliated Hospital of Guiyang Medical College
  • Hebei
    • Shijiazhuang, Hebei, China, 050051
      • The 3rd Hospital of Hebei Medical University
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Tongji Hospital, Tongji Medical college HuaZhong University of Science&Technology
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Nanjing No. 2 Hospital
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • The First Affiliated Hospital of Nanchang University
  • Jilin
    • Changchun, Jilin, China, 130021
      • The First Hospital of Jilin University
  • Liaoning
    • Shenyang, Liaoning, China, 110006
      • The Sixth People's Hospital of Shenyang
  • Shandong
    • Jinan, Shandong, China, 250021
      • Jinan Infectious Disease Hospital
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital, Sichuan University
  • Yunnan
    • Kunming, Yunnan, China, 650032
      • No.1 Hospital Affiliated to Kunming Medical College

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TAF; TAF + TDF placebo for up to 144 weeks	Drug: TAF; TAF 25 mg tablet administered orally once daily; Other Names: Vemlidy®; GS-7340; Drug: TDF Placebo; TDF placebo tablet administered orally once daily
Active Comparator: TDF; TDF + TAF placebo for up to 144 weeks	Drug: TDF; TDF 300 mg tablet administered orally once daily; Other Names: Viread®; Drug: TAF Placebo; TAF placebo tablet administered orally once daily
Experimental: 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.	Drug: TAF; TAF 25 mg tablet administered orally once daily; Other Names: Vemlidy®; GS-7340

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Treatment-emergent Proteinuria by Urinalysis (Dipstick) Through Week 48	Grades 1 (mild), 2 (moderate), and 3 (severe) were the highest treatment-emergent postbaseline grades for urine protein using the dipstick method.	Up to 48 weeks

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Investigators: Study Director: Gilead Study Director, Gilead Sciences

Publications and helpful links

General Publications

• Hou J, Ning Q, Duan Z, Chen Y, Xie Q, Wang FS, Zhang L, Wu S, Tang H, Li J, Lin F, Yang Y, Gong G, Flaherty JF, Gaggar A, Mo S, Cheng C, Camus G, Chen C, Huang Y, Jia J, Zhang M; GS-US-320-0110 and GS-US-320-0108 China Investigators. 3-year Treatment of Tenofovir Alafenamide vs. Tenofovir Disoproxil Fumarate for Chronic HBV Infection in China. J Clin Transl Hepatol. 2021 Jun 28;9(3):324-334. doi: 10.14218/JCTH.2020.00145. Epub 2021 Apr 28.

Helpful Links

• Gilead Clinical Trials Website

Study record dates

Study Major Dates

• Study Start (Actual): June 19, 2015
• Primary Completion (Actual): February 24, 2017
• Study Completion (Actual): September 18, 2023

Study Registration Dates

• First Submitted: July 14, 2016
• First Submitted That Met QC Criteria: July 14, 2016
• First Posted (Estimated): July 18, 2016

Study Record Updates

• Last Update Posted (Actual): November 1, 2023
• Last Update Submitted That Met QC Criteria: October 17, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Tenofovir; Hepatitis; Viread
• Additional Relevant MeSH Terms: Digestive System Diseases; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Hepatitis B; Hepatitis
• Other Study ID Numbers: GS-US-320-0108 (China); 2013-000626-63 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at https://www.gileadclinicaltrials.com/transparency-policy/
• IPD Sharing Time Frame: 18 months after study completion
• IPD Sharing Access Criteria: A secured external environment with username, password, and RSA code.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No