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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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03547908
Recruitment Status : Active, not recruiting
First Posted : June 6, 2018
Results First Posted : March 15, 2023
Last Update Posted : March 15, 2023
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Study Description
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Brief Summary:
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 HIV and hepatitis B virus (HBV) treatment naive, HIV-1 and HBV co-infected adults.

Condition or disease Intervention/treatment Phase
HIV-1/HBV Co-Infection Drug: B/F/TAF Drug: Placebo to match DTG Drug: Placebo to match F/TDF Drug: DTG Drug: F/TDF Drug: Placebo to match B/F/TAF Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 244 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : May 30, 2018
Actual Primary Completion Date : February 25, 2022
Estimated Study Completion Date : February 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: B/F/TAF
B/F/TAF + placebo to match DTG + placebo to match F/TDF 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 Name: 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: DTG+F/TDF
DTG + F/TDF + placebo to match 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 Name: 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
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 Name: Biktarvy®


Outcome Measures
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Primary Outcome Measures :
  1. 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.

  2. 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 on-treatment data were treated as HBV DNA ≥ 29 IU/mL.


Secondary Outcome Measures :
  1. 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 ]
  2. Change From Baseline in CD4 Cell Count at Week 48 [ Time Frame: Baseline; Week 48 ]
  3. Change From Baseline in CD4 Cell Count at Week 96 [ Time Frame: Baseline; Week 96 ]
  4. Change From Baseline in CD4 Percentage at Week 48 [ Time Frame: Baseline; Week 48 ]
  5. Change From Baseline in CD4 Percentage at Week 96 [ Time Frame: Baseline; Week 96 ]
  6. Percentage of Participants With Plasma HBV DNA < 29 IU/mL at Week 96 [ Time Frame: Week 96 ]
  7. 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.

  8. Percentage of Participants With ALT Normalization at Week 96 [ Time Frame: Week 96 ]
  9. 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.

  10. Percentage of Participants With HBsAg Loss at Week 96 [ Time Frame: Week 96 ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • HIV-1 co-infection:

    • Must be HIV antiretroviral treatment naive with plasma HIV-1 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 HBV treatment naive (defined as < 12 weeks of oral antiviral treatment)
    • Screening HBV DNA ≥ 2000 IU/mL
  • Hepatic transaminases (aspartate aminotransferase (AST) and 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.

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03547908


Locations
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Sponsors and Collaborators
Gilead Sciences
Investigators
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Study Director: Gilead Study Director Gilead Sciences
  Study Documents (Full-Text)

Documents provided by Gilead Sciences:
Study Protocol  [PDF] July 6, 2018
Statistical Analysis Plan  [PDF] March 31, 2022

More Information
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Additional Information:

Publications:
Avihingsanon, A. 2022. Week 48 results of a Phase 3 randomized controlled trial of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) vs dolutegravir + emtricitabine/tenofovir Disoproxil Fumarate (DTG+F/TDF) as initial treatment in HIV/HBV-coinfected adults (ALLIANCE). AIDS, 29 July 29-2 August 2022, Montréal, Québec, Canada.

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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT03547908    
Other Study ID Numbers: GS-US-380-4458
2018-000926-79 ( EudraCT Number )
First Posted: June 6, 2018    Key Record Dates
Results First Posted: March 15, 2023
Last Update Posted: March 15, 2023
Last Verified: February 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Hepatitis B
Coinfection
Hepatitis
Liver Diseases
Digestive System Diseases
Blood-Borne Infections
Communicable Diseases
Infections
Hepadnaviridae Infections
DNA Virus Infections
Virus Diseases
 Hepatitis, Viral, Human
Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Anti-HIV Agents
Anti-Retroviral Agents