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

NCT ID: NCT02836236

Last Updated: 2024-10-02

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

155 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-06-19

Study Completion Date

2023-09-18

Brief Summary

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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

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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.

Conditions

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HBV Chronic HBV Infection

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Double-Blind 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).

Group Type EXPERIMENTAL

TAF

Intervention Type DRUG

TAF 25 mg tablet administered orally once daily

TDF Placebo

Intervention Type DRUG

TDF placebo tablet administered orally once daily

Double-Blind TDF

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

Group Type ACTIVE_COMPARATOR

TDF

Intervention Type DRUG

TDF 300 mg tablet administered orally once daily

TAF Placebo

Intervention Type DRUG

TAF placebo tablet administered orally once daily

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.

Group Type EXPERIMENTAL

TAF

Intervention Type DRUG

TAF 25 mg tablet administered orally once daily

Interventions

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TAF

TAF 25 mg tablet administered orally once daily

Intervention Type DRUG

TDF

TDF 300 mg tablet administered orally once daily

Intervention Type DRUG

TAF Placebo

TAF placebo tablet administered orally once daily

Intervention Type DRUG

TDF Placebo

TDF placebo tablet administered orally once daily

Intervention Type DRUG

Other Intervention Names

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GS-7340 Vemlidy® Viread®

Eligibility Criteria

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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

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gilead Sciences

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

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Peking University First Hospital

Beijing, Beijing Municipality, China

Site Status

The Third Affiliated Hospital of Sun Yat-Sen University

Guangzhou, Guangdong, China

Site Status

The 1st Affiliated Hospital of Guangxi Medical University

Nanning, Guangxi Zhuang, China

Site Status

The Affiliated Hospital of Guiyang Medical College

Guiyang, Guiyang, China

Site Status

The 3rd Hospital of Hebei Medical University

Shijiazhuang, Hebei, China

Site Status

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

Wuhan, Hubei, China

Site Status

Nanjing No. 2 Hospital

Nanjing, Jiangsu, China

Site Status

The First Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, China

Site Status

The First Hospital of Jilin University

Changchun, Jilin, China

Site Status

The sixth People's Hospital of Shenyang

Shenyang, Liaoning, China

Site Status

Jinan Infectious Disease Hospital

Jinan, Shandong, China

Site Status

West China Hospital, Sichuan University

Chengdu, Sichuan, China

Site Status

No.1 Hospital Affiliated to Kunming Medical College

Kunming, Yunnan, China

Site Status

Beijing Ditan Hospital

Beijing, , China

Site Status

No. 302 PLA Hospital

Beijing, , China

Site Status

Peking University People's Hospital

Beijing, , China

Site Status

Beijing Friendship Hospital, Capital Medical University

Beijing, , China

Site Status

Beijing Youan Hospital, Capital Medical University

Beijing, , China

Site Status

XiangYa Hospital Central South University

Changsha, , China

Site Status

The 2nd Xiangya Hospital Central South University

Changsha, , China

Site Status

Guangzhou No.8 People's Hospital

Guangzhou, , China

Site Status

Nanfang Medical University, Nanfang Hospital

Guangzhou, , China

Site Status

The People's Hospital of Hainan Province

Haikou, , China

Site Status

Jiangsu Provincial People's Hospital

Nanjing, , China

Site Status

Rui Jin Hospital Shanghai Jiao Tong University School of Medicine

Shanghai, , China

Site Status

Shanghai Public Health Clinical Center

Shanghai, , China

Site Status

85 Hospital of People's Liberation Army

Shanghai, , China

Site Status

Shengjing Hospital of China Medical University

Shenyang, , China

Site Status

First Affiliated Hospital of Xi'an Jiaotong

Xi'an, , China

Site Status

Countries

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China

References

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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.

Reference Type BACKGROUND
PMID: 34221918 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 38779514 (View on PubMed)

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.

Reference Type DERIVED
PMID: 37771546 (View on PubMed)

Provided Documents

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Document Type: Study Protocol: Amendment 2.1

View Document

Document Type: Study Protocol: Amendment 3.1

View Document

Document Type: Study Protocol: Amendment 3.4

View Document

Document Type: Statistical Analysis Plan: Statistical Analysis Plan Week 48

View Document

Document Type: Statistical Analysis Plan: Statistical Analysis Plan Final

View Document

Related Links

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Other Identifiers

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2013-000626-63

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GS-US-320-0108 (China)

Identifier Type: -

Identifier Source: org_study_id

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