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

NCT02836249 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: GS-US-320-0110 (China)2013-000636-10
• Study Type: interventional
• Target: 181
• Locations: 1 country
• Sites: 25

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.

Conditions

HBV; Chronic HBV Infection

Keywords

Hepatitis; Tenofovir; Viread

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Hepatitis B Virus (HBV) DNA < 29 IU/mL at Week 48

  Week 48

Secondary Outcomes (4)

• Percentage of Participants With Hepatitis B e Antigen (HBeAg) Seroconversion to Antibody Against Hepatitis B e Antigen (Anti-HBe) at Week 48

  Week 48

• 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 at Week 48 in Serum Creatinine

  Baseline; Week 48

Other Outcomes (1)

• Percentage of Participants With Treatment-emergent Proteinuria by Urinalysis (Dipstick) Through Week 48

  Up to 48 weeks

Study Arms (3)

Double-Blind TAF

EXPERIMENTAL

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).

Drug: TAF; Drug: TDF Placebo

Double-Blind TDF

ACTIVE COMPARATOR

TDF 300 mg tablet + TAF placebo tablet once daily for up to 144 weeks (per amendment 3.1).

Drug: TDF; Drug: TAF Placebo

Open-label TAF

EXPERIMENTAL

All participants who complete the double-blind period will be eligible to receive open-label TAF until Week 384 of the study.

Drug: TAF

Interventions

TAF DRUG

TAF 25 mg tablet administered orally once daily

Also known as: GS-7340, Vemlidy®

Double-Blind TAF; Open-label TAF

TDF DRUG

TDF 300 mg tablet administered orally once daily

Also known as: Viread®

Double-Blind TDF

TAF Placebo DRUG

TAF placebo tablet administered orally once daily

Double-Blind TDF

TDF Placebo DRUG

TDF placebo tablet administered orally once daily

Double-Blind TAF

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (25)

Beijing Ditan Hospital

Beijing, 100015, China

Location

PLA 302 Hospital

Beijing, 100039, China

Location

Beijing Friendship Hospital, Capital Medical University

Beijing, 100050, China

Location

Beijing Youan Hospital, Capital Medical University

Beijing, 100069, China

Location

Xianya Hospital, Central South University

Changsha, 410008, China

Location

Guangzhou Eighth People's Hospital

Guangzhou, 510060, China

Location

Nanfang Medical University, Nanfang Hospital

Guangzhou, 510515, China

Location

No. 3 Hospital, Zhongshan Medical University

Guangzhou, 510630, China

Location

The Affiliated Hospital of Guiyang Medical College

Guiyang, 550004, China

Location

The People's Hospital of Hainan Province

Haikou, 570311, China

Location

The Second Xiangya Hospital of Central South University

Hunan, 410011, China

Location

The First Affiliated Hospital of Nanchang University

Jiangxi, 330006, China

Location

1st Hospital Jilin University

Jilin, 130021, China

Location

Jinan Infectious Disease Hospital

Jinan, 250021, China

Location

2nd Hospital of Nanjing City

Nanjing, 210003, China

Location

Jiangsu Province People's Hospital

Nanjing, 210029, China

Location

Ruijin Hospital, JiaoTong University School of Medicine

Shanghai, 200025, China

Location

Shanghai Public Health Clinical Center

Shanghai, 200083, China

Location

85 Hospital of People's Liberation Army

Shanghai, 200235, China

Location

Shengjing Hospital of China Medical University

Shenyang, 110004, China

Location

The Sixth People's Hospital of Shenyang

Shenyang, 110006, China

Location

3rd Hospital of Hebei Medical University

Shijiazhuang, 050051, China

Location

West China Hospital, Sichuan University

Sichuan, 610041, China

Location

First Affiliated Hospital of Xi'an Jiaotong University

Xi'an, 710061, China

Location

1st Affiliated Hospital Kunming Medical College

Yunnan, 650032, China

Location

Related Publications (3)

• 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.

  PMID: 34221918 BACKGROUND

• Hou J, Ning Q, Duan Z, Chen Y, Xie Q, Zhang L, Wu S, Tang H, Li J, Lin F, Yang Y, Gong G, Luo Y, Xie S, Wang H, Mateo R, Yazdi T, Abramov F, Yee LJ, Flaherty J, Chen C, Huang Y, Zhang M, Jia J. Five-year Treatment with Tenofovir Alafenamide Achieves High Rates of Viral Suppression, Alanine Aminotransferase Normalization, and Favorable Bone and Renal Safety in Chinese Chronic Hepatitis B Patients. J Clin Transl Hepatol. 2024 May 28;12(5):469-480. doi: 10.14218/JCTH.2023.00417. Epub 2024 Apr 15.

  PMID: 38779514 BACKGROUND

• Lim YS, Chan HLY, Ahn SH, Seto WK, Ning Q, Agarwal K, Janssen HLA, Pan CQ, Chuang WL, Izumi N, Fung S, Shalimar, Brunetto M, Hui AJ, Chang TT, Lim SG, Abramov F, Flaherty JF, Wang H, Yee LJ, Kao JH, Gane E, Hou J, Buti M. Tenofovir alafenamide and tenofovir disoproxil fumarate reduce incidence of hepatocellular carcinoma in patients with chronic hepatitis B. JHEP Rep. 2023 Jul 13;5(10):100847. doi: 10.1016/j.jhepr.2023.100847. eCollection 2023 Oct.

  PMID: 37771546 DERIVED

Related Links

• Gilead Clinical Trials Website

MeSH Terms

Conditions

Hepatitis

Interventions

tenofovir alafenamide; Tenofovir

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2016
• First Posted: July 18, 2016
• Study Start: June 19, 2015
• Primary Completion: March 21, 2017
• Study Completion: August 31, 2023
• Last Updated: October 15, 2024
• Results First Posted: April 17, 2018

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: 18 months after study completion
• Access Criteria: A secured external environment with username, password, and RSA code.

Locations

CN (25)