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)

Gilead Sciences

Status and phase: Completed; Phase 3

Conditions: HIV-1/HBV Co-Infection

Treatments: Drug: B/F/TAF; Drug: Placebo to match F/TDF; Drug: F/TDF; Drug: DTG; Drug: Placebo to match DTG; Drug: Placebo to match B/F/TAF

Study type: Interventional

Funder types: Industry

Identifiers

NCT03547908

2018-000926-79 (EudraCT Number)

GS-US-380-4458

Details and patient eligibility

About

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.

Enrollment: 244 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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244 participants in 4 patient groups

Blinded Phase: B/F/TAF

Experimental group

Description:

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.

Treatment:

Drug: Placebo to match DTG

Drug: Placebo to match F/TDF

Drug: B/F/TAF

Blinded Phase: DTG+F/TDF

Active Comparator group

Description:

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.

Treatment:

Drug: Placebo to match B/F/TAF

Drug: DTG

Drug: F/TDF

Open-label Extension Phase: B/F/TAF from B/F/TAF

Experimental group

Description:

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.

Treatment:

Drug: B/F/TAF

Open-label Extension Phase: B/F/TAF from DTG+F/TDF

Experimental group

Description:

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.

Treatment:

Drug: B/F/TAF