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
Overview
- Phase
- Phase 3
- Intervention
- B/F/TAF
- Conditions
- HIV-1/HBV Co-Infection
- Sponsor
- Gilead Sciences
- Enrollment
- 244
- Locations
- 69
- Primary Endpoint
- 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)
- Status
- Completed
- Last Updated
- last year
Overview
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 treatment-naïve and HIV-1 and hepatitis B virus (HBV) adults.
Investigators
Eligibility Criteria
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
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.
Arms & Interventions
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.
Intervention: B/F/TAF
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.
Intervention: Placebo to match DTG
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.
Intervention: Placebo to match F/TDF
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.
Intervention: DTG
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.
Intervention: F/TDF
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.
Intervention: Placebo to match B/F/TAF
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.
Intervention: B/F/TAF
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.
Intervention: B/F/TAF
Outcomes
Primary Outcomes
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.
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.
Secondary Outcomes
- Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 as Defined by the US FDA-Defined Snapshot Algorithm(Week 96)
- Change From Baseline in CD4 Cell Count at Week 48(Baseline, Week 48)
- Change From Baseline in CD4 Cell Count at Week 96(Baseline, Week 96)
- Change From Baseline in Percentage of CD4 Cells at Week 48(Baseline, Week 48)
- Change From Baseline in Percentage of CD4 Cells at Week 96(Baseline, Week 96)
- Percentage of Participants With Plasma HBV DNA < 29 IU/mL at Week 96(Week 96)
- Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Week 48 by American Association for the Study of Liver Diseases (AASLD) Criteria(Week 48)
- Percentage of Participants With ALT Normalization at Week 96(Week 96)
- Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Week 48(Week 48)
- Percentage of Participants With HBsAg Loss at Week 96(Week 96)