Study to Evaluate the Safety and Efficacy of Bictegravir/Emtricitabine/Tenofovir Alafenamide Versus Abacavir/Dolutegravir/Lamivudine in Human Immunodeficiency Virus-1 (HIV-1) Infected, Antiretroviral Treatment-Naive 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 a fixed dose combination (FDC) containing bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) versus a FDC containing abacavir/dolutegravir/lamivudine (ABC/DTG/3TC) in HIV-1 infected, antiretroviral treatment naive-adults.

Official Title
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A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of GS-9883/Emtricitabine/Tenofovir Alafenamide Versus Abacavir/Dolutegravir/Lamivudine in HIV-1 Infected, Antiretroviral Treatment-Naive Adults

Conditions
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HIV-1 Infection

Intervention / Treatment
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* Drug: ABC/DTG/3TC
* Drug: B/F/TAF
* Drug: ABC/DTG/3TC Placebo
* Drug: B/F/TAF Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Antiretroviral treatment naive (≤ 10 days of prior therapy with any antiretroviral agent 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 Plasma HIV-1 ribonucleic acid (RNA) levels ≥ 500 copies per milliliter (mL) at screening Adequate renal function: Estimated glomerular filtration rate ≥ 50 milliliter per minute (mL/min) (≥ 0.83 milliliter per second [mL/sec]) according to the Cockcroft-Gault formula Negative screening test for human leukocyte antigen (HLA) -B x 5701 allele provided by Gilead Sciences Key Exclusion Criteria: An opportunistic illness indicative of stage 3 HIV diagnosed within the 30 days prior to screening (refer to study protocol) Decompensated cirrhosis (e.g, ascites, encephalopathy, or variceal bleeding) Current alcohol or substance use judged by the Investigator to potentially interfere with subject study compliance Females who are pregnant (as confirmed by positive serum pregnancy test) Females who are breastfeeding Chronic Hepatitis B Virus (HBV) infection 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 + ABC/DTG/3TC placebo administered without regard to food for at least 144 weeks. | Drug: B/F/TAF<br>* 50/200/25 mg tablets administered orally, once daily, without regard to food<br>* Other names: Biktarvy®;Drug: ABC/DTG/3TC Placebo<br>* Tablets administered orally, once daily<br>|
| Active Comparator: ABC/DTG/3TC<br>ABC/DTG/3TC + B/F/TAF placebo administered without regard to food for at least 144 weeks. | Drug: ABC/DTG/3TC<br>* 600/50/300 milligrams (mg) tablets administered orally, once daily<br>* Other names: Triumeq®;Drug: B/F/TAF Placebo<br>* Tablets administered orally, once daily<br>|
| Experimental: Open-label Phase B/F/TAF to B/F/TAF<br>After Week 144, 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 will be given the option to receive open-label (OL) B/F/TAF for 96 weeks. After the Week 96 OL Visit, participants in a country where B/F/TAF is not commercially available will be given the option to continue OL B/F/TAF 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 tablets administered orally, once daily, without regard to food<br>* Other names: Biktarvy®;|
| Experimental: Open-label Phase ABC/DTG/3TC to B/F/TAF<br>After Week 144, 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 will be given the option to receive OL B/F/TAF for 96 weeks. After the Week 96 OL Visit, participants in a country where B/F/TAF is not commercially available will be given the option to continue OL B/F/TAF 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 tablets 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 Who Achieved HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm | 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieved HIV-1 RNA < 50 Copies/mL at Week 96 as Defined by the US FDA-Defined Snapshot Algorithm | The percentage of participants achieving HIV-1 RNA < 50 copies/mL at Week 96 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 96 | 
| Percentage of Participants Who Achieved HIV-1 RNA < 50 Copies/mL at Week 144 as Defined by the US FDA-Defined Snapshot Algorithm | The percentage of participants achieving HIV-1 RNA < 50 copies/mL at Week 144 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 144 | 
| Percentage of Participants Who Achieved HIV-1 RNA < 20 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm | The percentage of participants achieving HIV-1 RNA < 20 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 Who Achieved HIV-1 RNA < 20 Copies/mL at Week 96 as Defined by the US FDA-Defined Snapshot Algorithm | The percentage of participants achieving HIV-1 RNA < 20 copies/mL at Week 96 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 96 | 
| Percentage of Participants Who Achieved HIV-1 RNA < 20 Copies/mL at Week 144 as Defined by the US FDA-Defined Snapshot Algorithm | The percentage of participants achieving HIV-1 RNA < 20 copies/mL at Week 144 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 144 | 
| Change From Baseline in log10 HIV-1 RNA at Week 48 |  | Baseline, Week 48 | 
| Change From Baseline in log10 HIV-1 RNA at Week 96 |  | Baseline, Week 96 | 
| Change From Baseline in log10 HIV-1 RNA at Week 144 |  | Baseline, Week 144 | 
| 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+ Cell Count at Week 144 |  | Baseline, Week 144 | 
| Percentage Change From Baseline in Hip BMD at Week 48 |  | Baseline, Week 48 | 
| Percentage Change From Baseline in Hip BMD at Week 96 |  | Baseline, Week 96 | 
| Percentage Change From Baseline in Hip BMD at Week 144 |  | Baseline, Week 144 | 
| Percentage Change From Baseline in Spine BMD at Week 48 |  | Baseline, Week 48 | 
| Percentage Change From Baseline in Spine BMD at Week 96 |  | Baseline, Week 96 | 
| Percentage Change From Baseline in Spine BMD at Week 144 |  | Baseline, Week 144 | 
| Percentage of Participants Who Achieved HIV-1 RNA < 50 Copies/mL at Week 48 Open-Label as Defined by Missing = Excluded Algorithm | The percentage of participants with HIV-1 RNA < 50 copies/mL was analyzed using Missing = Excluded for imputing missing HIV-1 RNA values using the All B/F/TAF Analysis Set. All missing data was excluded in the computation of the percentages (ie, missing data points were excluded from both the numerator and denominator in the computation). The denominator for percentages at a visit was the number of participants in the all B/F/TAF analysis set with non-missing HIV-1 RNA value at that visit. | Baseline, open-label Week 48 | 
| Percentage of Participants Who Achieved HIV-1 RNA < 50 Copies/mL at Week 48 Open-Label as Defined by Missing = Failure Algorithm | The percentage of participants with HIV-1 RNA < 50 copies/mL was analyzed using Missing = Failure for imputing missing HIV-1 RNA values using the All B/F/TAF Analysis Set. All missing data was treated as HIV-1 RNA ≥ 50 copies/mL. The denominator for percentages was the number of participants in all B/F/TAF analysis set. | Baseline, open-label Week 48 | 
| Percentage of Participants Who Achieved HIV-1 RNA < 50 Copies/mL at Week 96 Open-Label as Defined by Missing = Excluded Algorithm | The percentage of participants with HIV-1 RNA < 50 copies/mL was analyzed using Missing = Excluded for imputing missing HIV-1 RNA values using the All B/F/TAF Analysis Set. All missing data was excluded in the computation of the percentages (ie, missing data points were excluded from both the numerator and denominator in the computation). The denominator for percentages at a visit was the number of participants in the all B/F/TAF analysis set with non-missing HIV-1 RNA value at that visit. | Baseline, open-label Week 96 | 
| Percentage of Participants Who Achieved HIV-1 RNA < 50 Copies/mL at Week 96 Open-Label as Defined by Missing = Failure Algorithm | The percentage of participants with HIV-1 RNA < 50 copies/mL was analyzed using Missing = Failure for imputing missing HIV-1 RNA values using the All B/F/TAF Analysis Set. All missing data was treated as HIV-1 RNA ≥ 50 copies/mL. The denominator for percentages was the number of participants in all B/F/TAF analysis set. | Baseline, open-label Week 96 | 
| Change From Baseline in CD4+ Cell Count at Week 48 Open-Label |  | Baseline, open-label Week 48 | 
| Change From Baseline in CD4+ Cell Count at Week 96 Open-Label |  | Baseline, open-label Week 96 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV