Study to Compare Tenofovir Alafenamide (TAF) Versus Tenofovir Disoproxil Fumarate (TDF) in Participants With Chronic Hepatitis B Infection Who Are Negative for Hepatitis B e Antigen

September 22, 2023 updated by: Gilead Sciences

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Study GS-US-320-0108 is a multi-center clinical trial, planned to enroll participants in multiple countries, including China. However, due to the review timeline difference in China, full enrollment was reached in the main study before China was able to participate. Therefore, details for the China cohort was registered separately (NCT02836236) on ClinicalTrials.gov as the China cohort will not be part of the main study analysis.

Study Type

Interventional

Enrollment (Actual)

426

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • Victoria
      • Clayton, Victoria, Australia, 3168
        • Monash Medical Centre
      • Fitzroy, Victoria, Australia, 3065
        • St. Vincent's Hospital
      • Parkville, Victoria, Australia, 3050
        • Royal Melbourne Hospital
    • Western Australia
      • Nedlands, Western Australia, Australia, 6009
        • Sir Charles Gairdner Hospital
      • Perth, Western Australia, Australia, 6000
        • Royal Perth Hospital
  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 4Z6
        • University of Calgary
      • Edmonton, Alberta, Canada, T6G 2X8
        • Zeidler Ledcor Centre Division of Gastroenterology
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 1M9
        • Gordon and Leslie Diamond Health Care Centre
      • Vancouver, British Columbia, Canada, V6Z 2C7
        • Vancouver Infectious Disease Research and Care Centre
      • Vancouver, British Columbia, Canada, V6Z 2K5
        • Gastrointestinal Research Institute (GIRI)
      • Vancouver, British Columbia, Canada, V5Z 1H3
        • Liver and Intestinal Research Centre
      • Vancouver, British Columbia, Canada, V6A 4B6
        • Dr. John Farley Inc.
    • Manitoba
      • Winnipeg, Manitoba, Canada, R3E 3P4
        • University of Manitoba
    • Ontario
      • Toronto, Ontario, Canada, M5G 2C4
        • Toronto General Hospital
      • Toronto, Ontario, Canada, M5T 2S8
        • Inspiration Research Limited
      • Toronto, Ontario, Canada, M6H 3M1
        • Toronto Liver Centre
  • France
      • Lyon cedex 04, France, 69317
        • Hôpital de la Croix Rousse
      • Strasbourg, France, 67000
        • Hopital Civil de Strasbourg- CHU Service
  • Hong Kong
      • Kwai Chung, Hong Kong
        • Princess Margaret Hospital
      • Shatin, Hong Kong
        • Prince of Wales Hospital
      • Tai Po, Hong Kong
        • Alice Ho Miu Ling Nethersole Hospital
    • Hong Kong SAR
      • Hong Kong, Hong Kong SAR, Hong Kong
        • Queen Mary Hospital
  • India
      • Chandigarh, India, 160012
        • Postgraduate Institute of Medical Education and Research
      • New Delhi, India, 110070
        • Institute of Liver and Biliary Sciences
    • Andhra Pradesh
      • Hyderabad, Andhra Pradesh, India, 500004
        • Global Hospitals
      • Hyderabad, Andhra Pradesh, India, 500058
        • Centre for Liver Research & Diagnostic, Deccan College of Medical Sciences and Allied Hospitals
    • Delhi
      • New Delhi, Delhi, India, 110029
        • All India Institute of Medical Sciences
    • Gujarat
      • Surat, Gujarat, India, 395002
        • Nirmal Hospital
    • Maharastra
      • Mumbai, Maharastra, India, 400012
        • Seth GS medical college and KEM Hospital
    • Mumbai
      • Parel, Mumbai, India, 400 012
        • Global Hospital Super Specialty & Transplant Centre
    • Rajasthan
      • Jaipur, Rajasthan, India, 302001
        • S. R Kalla Memorial Gastro & General Hospital
    • West Bengal
      • Kolkata, West Bengal, India, 700020
        • Institute of Post Graduate Medical Education And Research
  • Italy
      • Bologna, Italy, 40138
        • Azienda Ospedaliera S. Orsola - Malpighi
      • Foggia, Italy, 71122
        • Azienda Ospedaliero Universitaria Ospedali
      • Pisa, Italy, 56124
        • Azienda Ospedaliero- Universitaria Pisana
    • Foggia
      • San Giovanni Rotondo, Foggia, Italy, 71013
        • IRCCS Ospedale Casa Sollievo della Sofferenza
  • Japan
      • Kitakyushu, Japan, 803-8505
        • Shin-Kokura Hospital
      • Kobe, Japan, 650-0047
        • Kobe City Medical Center General Hospital
      • Musashino, Japan, 180-8610
        • Japan Red Cross Musashino Hospital
      • Nishinomiya, Japan, 663-8501
        • The Hospital of Hyogo College of Medicine
      • Osaka, Japan, 543-8555
        • Osaka Red Cross Hospital
      • Sapporo, Japan, 060-8648
        • Hokkaido University Hospital
      • Tokyo, Japan, 113-8519
        • Medical Hospital of Tokyo Medical and Dental University
    • Fukuoka-ken
      • Kurume-shi, Fukuoka-ken, Japan, 830-0011
        • Kurume University Hospital
    • Fukuoka-shi
      • Fukuoka, Fukuoka-shi, Japan, 812-8582
        • Kyushu University Hospital Fukuoka
    • Nagasaki
      • Omura-shi, Nagasaki, Japan, 856-8562
        • National Hospital Organization Nagasaki Medical Center
    • Osaka
      • Suita, Osaka, Japan, 565-0871
        • Osaka University Hospital
  • Korea, Republic of
      • Daegu, Korea, Republic of, 41944
        • Kyungpook National University Hospital
      • Daegu, Korea, Republic of, 42601
        • Keimyung University Dongsan Medical Center
      • Seoul, Korea, Republic of, 05505
        • Asan Medical Center
      • Seoul, Korea, Republic of, 06973
        • Chung-Ang University Hospital
      • Seoul, Korea, Republic of, 08308
        • Korea University Guro Hospital
      • Seoul, Korea, Republic of, 06351
        • Samsung Medical Center
      • Seoul, Korea, Republic of, 06273
        • Gangnam Severance Hospital
      • Seoul, Korea, Republic of, 06591
        • Seoul Saint Mary Hospital
      • Seoul, Korea, Republic of, 03722
        • Yonsei University, Severance Hospital
    • Gyeongsangnam-do
      • Yangsan, Gyeongsangnam-do, Korea, Republic of, 50612
        • Pusan National University Yangsan Hospital
  • New Zealand
      • Auckland, New Zealand, 1010
        • Auckland Clinical Studies Limited
  • Poland
      • Bialystok, Poland, 15-540
        • Uniwersytecki Szpital Kliniczny w Bialymstoku Klinika
      • Chorzow, Poland, 41-500
        • Szpital Specjalistyczny w Chorzowie Oddział
      • Lodz, Poland, 91-347
        • SPZOZ, Wojewódzki Specjalistyczny Szpital
      • Wroclaw, Poland, 50-349
        • Centrum Badan Klinicznych - Przychodnia Badan
  • Romania
      • Bucuresti, Romania, 030303
        • Centrul Medical de Diagnostic si Tratament "Dr. Victor Babes"
      • Bucuresti, Romania, 21105
        • Institutul National de Boli Infectioase Prof.Dr. Matei Bals
      • Constanta, Romania, 900708
        • Spitatul Clinic de Boli Infectioase Constanta
      • Iasi, Romania, 700506
        • Gastromedica Srl
    • Bucuresti
      • Bucharest, Bucuresti, Romania, 021105
        • Institutul National De Boli Infectioase "Prof. Dr. Matei Bals"
  • Russian Federation
      • Moscow, Russian Federation, 119991
        • 1st Moscow State Medical University University Clinical Hospital #3
      • Moscow, Russian Federation, 121293
        • Limited Liability Company "Modern Medicine Clinic"
      • Moscow, Russian Federation, 125367
        • Infectious Clinical Hospital #1 of Moscow Healthcare Department
      • Novosibirsk, Russian Federation, 630087
        • State Novosibirsk regional clinical hospital
      • Novosibirsk, Russian Federation, 630084
        • Novosibirsk State Medical University
      • Novosibirsk, Russian Federation, 630091
        • Scientific Research Institute of Clinical Immunology
      • Saint-Petersburg, Russian Federation, 197376
        • Research Institute of Influenza
      • Saint-Petersburg, Russian Federation, 191167
        • Clinical Infectious Hospital named after S.P.Botkin
      • Saint-Petersburg, Russian Federation, 194044
        • Kirov Medical Military Academy
    • Novosibirsk
      • Koltsovo, Novosibirsk, Russian Federation, 630559
        • Infection Center LLC Building 20, MSH #163 Territory Koltsovo
  • Spain
      • Barcelona, Spain, 08035
        • Hospital Universitari Vall d'Hebron
  • Taiwan
      • Hualien City, Taiwan, 970
        • Hualien Tzu Chi Hospital
      • Kaohsiung, Taiwan, 807
        • Kaohsiung Medical University Hospital
      • Taichung, Taiwan, 40705
        • Taichung Veterans General Hospital
      • Tainan, Taiwan, 704
        • National Cheng Kung University Hospital
      • Taipei, Taiwan, 10002
        • National Taiwan University Hospital
  • Turkey
      • Ankara, Turkey, 06590
        • Ankara Üniversitesi Gastroenteroloji Bilim Dalı Cebeci
      • Bursa, Turkey, 16059
        • Uludag Üniversitesi Tıp Fakültesi Gastroenteroloji
      • Istanbul, Turkey, 34098
        • Istanbul Universitesi Cerrahpassa Tip Fakultesi Hastanesi
      • Izmir, Turkey, 35040
        • Ege Universitesi Tip Fakultesi Hastanesi
    • Diyarbakri
      • Diyarbakir, Diyarbakri, Turkey, 21280
        • Dicle University Medical Faculty Department of Infectious Diseases
  • United Kingdom
      • London, United Kingdom, SE5 9RS
        • King's College Hospital
      • London, United Kingdom, E1 1BB
        • Barts and The London NHS Trust Royal London Hospital
    • Nottinghamshire
      • Nottingham, Nottinghamshire, United Kingdom, NG7 2UH
        • Nottingham University Hospitals Nhs Trust
  • United States
    • California
      • Los Angeles, California, United States, 90020
        • Asian Pacific Liver Center
      • Palo Alto, California, United States, 94304
        • Stanford University Medical Center
      • Pasadena, California, United States, 91105
        • Huntington Medical Research Institutes
      • San Diego, California, United States, 92105
        • Research and Education, Inc.
      • San Francisco, California, United States, 94110
        • University California San Francisco (UCSF)
      • San Jose, California, United States, 95128
        • Silicon Valley Research Institute
    • Florida
      • Miami, Florida, United States, 33136
        • University of Miami
    • Maryland
      • Catonsville, Maryland, United States, 21228
        • Digestive Disease Associates, PA
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Henry Ford Health System
    • New Jersey
      • Hillsborough, New Jersey, United States, 08844
        • ID Care
    • New York
      • Flushing, New York, United States, 11354
        • Sing Chan Private Practice
      • Flushing, New York, United States, 11355
        • New Discovery, LLC
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Xiaoli Ma, PC
    • Virginia
      • Richmond, Virginia, United States, 23249
        • Hunter Holmes McGuire VA DVMC

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 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 Baseline.
  • Adequate renal function.
  • Normal electrocardiogram (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, human immunodeficiency 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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: TAF 25 mg
TAF + TDF placebo for 96 weeks (per amendment 1 & 2) or 144 weeks (per amendment 3).
Drug: TAF
25 mg tablet administered orally once daily
Other Names:
  • Vemlidy®
  • GS-7340
Drug: TDF Placebo
Tablet administered orally once daily
Active Comparator: TDF 300 mg
TDF + TAF placebo for 96 weeks (per amendment 1 & 2) or 144 weeks (per amendment 3).
Drug: TDF
300 mg tablet administered orally once daily
Other Names:
  • Viread®
Drug: TAF Placebo
Tablet administered orally once daily
Experimental: Open-label TAF

All participants who complete the double-blind period (96 weeks or 144 weeks) will be eligible to receive open-label TAF until Week 384 of the study.

After the end of study treatment, participants can either switch to commercially available anti-HBV treatments in their country or will be followed every 4 weeks, for up to 24 weeks off treatment (treatment-free follow-up (TFFU)) for safety assessment.
Drug: TAF
25 mg tablet administered orally once daily
Other Names:
  • Vemlidy®
  • GS-7340

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Hepatitis B Virus (HBV) DNA < 29 IU/mL
Time Frame: Week 48
The primary efficacy endpoint was determined by the achievement of HBV DNA < 29 IU/mL at Week 48.
Week 48

Secondary Outcome Measures

Outcome Measure
Time Frame
Percent Change From Baseline in Spine BMD at Week 48
Time Frame: Baseline, Week 48
Baseline, Week 48
Change From Baseline in Serum Creatinine at Week 48
Time Frame: Baseline, Week 48
Baseline, Week 48
Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48
Time Frame: Baseline, 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
Time Frame: Up to 48 weeks
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

This is where you will find people and organizations involved with this study.

Sponsor

Gilead Sciences

Investigators

  • Study Director: Gilead Study Director, Gilead Sciences

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 12, 2013

Primary Completion (Actual)

September 30, 2015

Study Completion (Actual)

August 31, 2022

Study Registration Dates

First Submitted

August 20, 2013

First Submitted That Met QC Criteria

September 9, 2013

First Posted (Estimated)

September 12, 2013

Study Record Updates

Last Update Posted (Actual)

September 25, 2023

Last Update Submitted That Met QC Criteria

September 22, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GS-US-320-0108
  • 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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