Safety and Efficacy of Bictegravir/Emtricitabine/Tenofovir Alafenamide Versus Dolutegravir + Emtricitabine/Tenofovir Disoproxil Fumarate in Treatment Naive, HIV-1 and Hepatitis B Co-Infected Adults (Alliance)

February 27, 2025 updated by: Gilead Sciences

A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of Fixed Dose Combination of Bictegravir/Emtricitabine/Tenofovir Alafenamide Versus Dolutegravir + Emtricitabine/Tenofovir Disoproxil Fumarate in Treatment Naïve, HIV-1 and Hepatitis B Co-Infected Adults

The primary objective of this study is to evaluate the efficacy of fixed-dose combination (FDC) of bictegravir/emtricitabine/ tenofovir alafenamide (B/F/TAF) versus dolutegravir (DTG) + emtricitabine/tenofovir disoproxil fumarate (F/TDF) in treatment-naïve and HIV-1 and hepatitis B virus (HBV) adults.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

244

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

  • China
      • Beijing, China, 100015
        • Beijing Ditan Hospital Capital Medical University
      • Beijing, China, 100069
        • Beijing Youan Hospital, Capital Medical University
      • Beijing, China, 100730
        • Peking Union Medical College Hospital, Chinese Academy of Medical Sciences
      • Changsha, China, 410005
        • The First Hospital of Changsha
      • Chengdu, China, 610066
        • Chengdu Public Health Clinical Center
      • Guangzhou, China, 510060
        • Guangzhou Eighth People's Hospital
      • Hangzhou, China
        • 1st Affiliated Hospital of Zhejiang University
      • Nanjing, China
        • The Second Hospital of Nanjing
      • Shanghai, China, 201058
        • Shanghai Public Health Clinical Center
      • Shenzhen, China, 518040
        • Third People's Hospital Of Shenzhen
  • Dominican Republic
      • Santo Domingo, Dominican Republic, 10103
        • Instituto Dominicano de Estudios Virologicos (IDEV)
  • France
      • Lyon, France, 69004
        • Hôpital de la Croix Rousse
  • Greece
      • Athens, Greece, 11526
        • Korgialenio-Benakio Greek Red Cross General Hospital
      • Athens, Greece, 11527
        • Laiko General Hospital
      • Athens, Greece, 10676
        • Evaggelismos General Hospital of Athens
      • Thessaloniki, Greece, 546 36
        • AHEPA University Hospital of Thessaloniki
  • Hong Kong
      • Hong Kong, Hong Kong
        • Prince of Wales Hospital
      • Hong Kong, Hong Kong
        • Queen Elizabeth Hospital (QEH)
      • Kowloon, Hong Kong
        • Princess Margaret Hospital
  • Japan
      • Aichi, Japan, 460-0001
        • National Hospital Organization Nagoya Medical Center
      • Okinawa, Japan, 903-0215
        • University of the Ryukyus hospital
      • Osaka, Japan, 540-0006
        • National Hospital Organization Osaka National Hospital
      • Osaka, Japan, 534-0021
        • Osaka City General Hospital
      • Tokyo, Japan, 113-8431
        • Juntendo University Hospital
      • Tokyo, Japan, 105-8471
        • The Jikei University Hospital
      • Tokyo, Japan, 162-8655
        • Center Hospital of the National Center for Global Health and Medicine
      • Yokohama, Japan, 236-0004
        • Yokohama City University Hospital
  • Korea, Republic of
      • Busan, Korea, Republic of, 49241
        • Pusan National University Hospital
      • Seoul, Korea, Republic of, 06591
        • The Catholic University of Korea, Seoul St. Mary's Hospital
  • Malaysia
      • Ipoh, Malaysia, 31350
        • Hospital Raja Permaisuri Bainun
      • Kota Bahru, Malaysia, 15580
        • Hospital Raja Perempuan Zainab II
      • Kota Kinabalu, Malaysia, 88200
        • Queen Elizabeth Hospital
      • Kuala Lumpur, Malaysia, 50603
        • University Malaya Medical Centre
      • Kuala Lumpur, Malaysia, 53000
        • Hospital Kuala Lumpur
      • Kuala Terengganu, Malaysia, 20400
        • Hospital Sultanah Nur Zahirah
      • Kuching, Malaysia, 93586
        • Sarawak General Hospital
      • Pulau Pinang, Malaysia, 10450
        • Hospital Pulau Pinang
      • Sungai Buloh, Malaysia, 47000
        • Sungai Buloh Hospital
  • Puerto Rico
      • San Juan, Puerto Rico, 00909
        • HOPE Clinical Research
  • Spain
      • Barcelona, Spain, 08036
        • Hospital Clinic de Barcelona
      • Cartagena, Spain
        • Hospital General Universitario Santa Lucia
      • Madrid, Spain, 28040
        • Fundacion Jimenez Diaz
      • Madrid, Spain, 28041
        • Hospital Universitario 12 de Octubre
      • Madrid, Spain, 28046
        • Hospital Universitario La Paz
      • Santa Cruz de Tenerife, Spain, 38320
        • Hospital de Canarias
      • Valencia, Spain, 46014
        • Hospital General Universitario de Valencia
      • Vigo, Spain, 36312
        • CHUVI - Hospital Universitario Alvaro Cunqueiro
  • Taiwan
      • Kaohsiung, Taiwan, 81362
        • Kaohsiung Veterans General Hospital
      • Kaohsiung, Taiwan, 80756
        • Kaohsiung Medical University Chung-Ho Memorial Hospital
      • New Taipei City, Taiwan, 22060
        • Far Eastern Memorial Hospital
      • Taichung, Taiwan, 40705
        • Taichung Veterans General Hospital
      • Tainan, Taiwan, 70403
        • National Cheng Kung University Hospital
      • Taipei, Taiwan, 10048
        • National Taiwan University Hospital
      • Taipei, Taiwan, 10844
        • Taipei City Hospital Linsen, Chinese Medicine and Kunming Branch
      • Taipei City, Taiwan, 11217
        • Taipei Veterans General Hospital
      • Taoyuan City, Taiwan, 33004
        • Ministry of Health and Welfare Taoyuan General Hospital
  • Thailand
      • Bangkok, Thailand, 10700
        • Siriraj Hospital
      • Bangkok, Thailand, 10330
        • Thai Red Cross AIDS Research Centre (HIV-NAT)
      • Bangkok, Thailand, 10400
        • Faculty of Medicine Ramathibodi Hospital, Mahidol University
      • Chiang Mai, Thailand, 50200
        • Faculty of Medicine, Chiang Mai University
      • Chiang Rai, Thailand, 57000
        • Chiang Rai Reginal Hospital
      • Khon Kaen, Thailand, 40002
        • Srinagarind Hospital
      • Nonthaburi, Thailand, 11000
        • Bamrasnaradura Infectious Diseases Institute
  • Turkey
      • Istanbul, Turkey, 34098
        • Istanbul University Cerrahpasa Medical Faculty
      • Istanbul, Turkey, 81190
        • Marmara University Pendik Training and Research Hospital
  • United States
    • Florida
      • Fort Pierce, Florida, United States, 34982
        • Midway Immunology & Research
      • West Palm Beach, Florida, United States, 33401
        • Triple O Research Institute, P.A.
    • Michigan
      • Berkley, Michigan, United States, 48072
        • Be Well Medical Center
    • Texas
      • Houston, Texas, United States, 77098
        • The Crofoot Research Center, INC (DBA: Gordon E. Crofoot MD PA)

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:

  • Human immunodeficiency virus type 1 (HIV-1) co-infection:

    • Must be HIV antiretroviral treatment naive with plasma HIV-1 ribonucleic acid (RNA) ≥ 500 copies/mL at screening
    • ≤ 10 days of prior therapy with any antiretroviral agent, including lamivudine and entecavir, following a diagnosis of HIV-1 infection (except the use for pre-exposure prophylaxis (PrEP) or post-exposure prophylaxis (PEP), up to one month prior to screening)
    • Screening genotype report must show sensitivity to emtricitabine (FTC) and tenofovir (TFV). This report will be provided by Gilead Sciences. Alternatively, if genotype results from a local laboratory obtained ≤ 90 days prior to screening visit date show sensitivity to these drugs, this genotype will be acceptable to fulfill this inclusion criterion in the event that the genotype obtained at screening is not yet available and all other inclusion/exclusion criteria have been confirmed

  • HBV co-infection:

    • Must be hepatitis B virus (HBV) treatment naive (defined as < 12 weeks of oral antiviral treatment)
    • Screening HBV deoxyribonucleic acid (DNA) ≥ 2000 IU/mL
  • Hepatic transaminases (aspartate aminotransferase (AST) and alanine aminotransferase (ALT)) ≤ 10 x upper limit of normal (ULN)
  • Total bilirubin ≤ 2.5 x ULN

Key Exclusion Criteria:

  • Hepatitis C virus (HCV) antibody positive and HCV RNA detectable
  • Individuals experiencing decompensated cirrhosis (eg, ascites, encephalopathy, or variceal bleeding) or with Child-Pugh-Turcotte (CPT) C impairment
  • Current alcohol or substance use judged by the Investigator to potentially interfere with study compliance
  • Active, serious infections (other than HIV-1 and HBV infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Day 1
  • Participation in any other clinical trial, including observational studies, without prior approval from the sponsor is prohibited while participating in this trial

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: Blinded Phase: B/F/TAF
Participants who are HIV-1 and HBV co-infected and treatment-naïve will receive Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) fixed-dose combination (FDC) tablet in addition to placebo to match (PTM) dolutegravir (DTG) tablet and PTM FDC emtricitabine/ tenofovir desoproxil fumarate (F/TDF) tablet for 96 weeks.
Drug: B/F/TAF
50/200/25 mg B/F/TAF FDC tablet administered orally once daily, without regard to food
Other Names:
  • Biktarvy®
Drug: Placebo to match DTG
Tablet administered orally once daily, without regard to food
Drug: Placebo to match F/TDF
Tablet administered orally once daily, without regard to food
Active Comparator: Blinded Phase: DTG+F/TDF
Participants who are HIV-1 and HBV co-infected and treatment-naïve will receive DTG and FDC F/TDF in addition to PTM B/F/TAF for 96 weeks.
Drug: DTG
50 mg tablet administered orally once daily, without regard to food
Drug: F/TDF
200/300 mg tablet administered orally once daily, without regard to food
Other Names:
  • Truvada®
Drug: Placebo to match B/F/TAF
Tablet administered orally once daily, without regard to food
Experimental: Open-label Extension Phase: B/F/TAF from B/F/TAF
After Week 96, participants will continue to take their blinded study drug and attend visits every 12 weeks until the End of Blinded Treatment Visit. Following the End of Blinded Treatment Visit, participants in a country where B/F/TAF FDC is not available will be given the option to receive B/F/TAF FDC in an open-label extension phase for up to 48 weeks, or until the product becomes accessible through an access program, or until Gilead elects to discontinue the study in that country, whichever occurs first.
Drug: B/F/TAF
50/200/25 mg B/F/TAF FDC tablet administered orally once daily, without regard to food
Other Names:
  • Biktarvy®
Experimental: Open-label Extension Phase: B/F/TAF from DTG+F/TDF
After Week 96, participants will continue to take their blinded study drug and attend visits every 12 weeks until the End of Blinded Treatment Visit. Following the End of Blinded Treatment Visit, participants in a country where B/F/TAF FDC is not available will be given the option to receive B/F/TAF FDC in an open-label extension phase for up to 48 weeks, or until the product becomes accessible through an access program, or until Gilead elects to discontinue the study in that country, whichever occurs first.
Drug: B/F/TAF
50/200/25 mg B/F/TAF FDC tablet administered orally once daily, without regard to food
Other Names:
  • Biktarvy®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm (Co-primary Endpoint)
Time Frame: Week 48
The percentage of participants achieving HIV-1 RNA < 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. Percentages were rounded-off.
Week 48
Percentage of Participants With Plasma Hepatitis B Virus (HBV) DNA < 29 IU/mL at Week 48 as Defined by Missing = Failure Approach (Co-primary Endpoint)
Time Frame: Week 48
This outcome measure was analyzed using a Missing = Failure approach. In this approach, all missing data were treated as HBV DNA ≥ 29 IU/mL. Percentages were rounded-off.
Week 48

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in CD4 Cell Count at Week 48
Time Frame: Baseline, Week 48
Baseline, Week 48
Change From Baseline in CD4 Cell Count at Week 96
Time Frame: Baseline, Week 96
Baseline, Week 96
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 as Defined by the US FDA-Defined Snapshot Algorithm
Time Frame: Week 96
The percentage of participants achieving HIV-1 RNA < 50 copies/mL at Week 96 was analyzed using the snapshot algorithm, which was defined as a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. Percentages were rounded-off.
Week 96
Change From Baseline in Percentage of CD4 Cells at Week 48
Time Frame: Baseline, Week 48
Baseline, Week 48
Change From Baseline in Percentage of CD4 Cells at Week 96
Time Frame: Baseline, Week 96
Baseline, Week 96
Percentage of Participants With Plasma HBV DNA < 29 IU/mL at Week 96
Time Frame: Week 96
This outcome measure was analyzed using a Missing = Failure approach. In this approach, all missing data were treated as HBV DNA ≥ 29 IU/mL. Percentages were rounded-off.
Week 96
Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Week 48 by American Association for the Study of Liver Diseases (AASLD) Criteria
Time Frame: Week 48
ALT normalization was defined as an ALT value that changed from above the normal range at baseline to within the normal range at the given post baseline visit. The upper limit of the normal range (ULN) for ALT using the 2018 AASLD normal range was ≤ 25 U/L for females and ≤ 35 U/L for males. The Missing = Failure approach was used for this analysis. Percentages were rounded off.
Week 48
Percentage of Participants With ALT Normalization at Week 96
Time Frame: Week 96
ALT normalization was defined as an ALT value that changed from above the normal range at baseline to within the normal range at the given post baseline visit. The upper limit of the normal range (ULN) for ALT using the 2018 AASLD normal range was ≤ 25 U/L for females and ≤ 35 U/L for males. The Missing = Failure approach was used for this analysis. Percentages were rounded-off.
Week 96
Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Week 48
Time Frame: Week 48
HBsAg loss was defined as qualitative HBsAg changing from positive at baseline to negative at a post baseline visit. HBsAg seroconversion was defined as HBsAg loss and HBsAb changes from negative or missing at baseline to positive at a post baseline visit. The Missing = Failure approach was used for this analysis. Percentages were rounded-off.
Week 48
Percentage of Participants With HBsAg Loss at Week 96
Time Frame: Week 96
HBsAg loss was defined as qualitative HBsAg changing from positive at baseline to negative at a post baseline visit. HBsAg seroconversion was defined as HBsAg loss and HBsAb changes from negative or missing at baseline to positive at a post baseline visit. The Missing = Failure approach was used for this analysis. Percentages were rounded-off.
Week 96

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)

May 30, 2018

Primary Completion (Actual)

February 25, 2022

Study Completion (Actual)

March 7, 2024

Study Registration Dates

First Submitted

May 24, 2018

First Submitted That Met QC Criteria

May 24, 2018

First Posted (Actual)

June 6, 2018

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

February 27, 2025

Last Verified

February 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GS-US-380-4458
  • 2018-000926-79 (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#Commitment

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

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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