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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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HIV-1/HBV Co-Infection

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: B/F/TAF<br>B/F/TAF + placebo to match DTG + placebo to match F/TDF for 96 weeks. | Drug: B/F/TAF<br>* 50/200/25 mg B/F/TAF FDC tablet administered orally once daily, without regard to food<br>* Other names: Biktarvy®;Drug: Placebo to match DTG<br>* Tablet administered orally once daily, without regard to food<br>Drug: Placebo to match F/TDF<br>* Tablet administered orally once daily, without regard to food<br>|
| Active Comparator: DTG+F/TDF<br>DTG + F/TDF + placebo to match B/F/TAF for 96 weeks. | Drug: DTG<br>* 50 mg tablet administered orally once daily, without regard to food<br>Drug: F/TDF<br>* 200/300 mg tablet administered orally once daily, without regard to food<br>* Other names: Truvada®;Drug: Placebo to match B/F/TAF<br>* Tablet administered orally once daily, without regard to food<br>|
| Experimental: Open-label Extension Phase: B/F/TAF<br>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<br>* 50/200/25 mg B/F/TAF FDC tablet administered orally once daily, without regard to food<br>* Other names: Biktarvy®;|

What is the study measuring?
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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) | 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. | 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) | 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. | Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 CD4 Percentage at Week 48 |  | Baseline; Week 48 | 
| Change From Baseline in CD4 Percentage 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 | 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. | 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 | 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. | Week 48 | 
| Percentage of Participants With HBsAg Loss at Week 96 |  | Week 96 |