Study to Evaluate the Safety and Efficacy of Bictegravir/Emtricitabine/Tenofovir Alafenamide Versus Dolutegravir + Emtricitabine/Tenofovir Alafenamide in Human Immunodeficiency Virus (HIV-1) Infected, Antiretroviral Treatment-Naive Adults

Study Overview
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Brief Summary
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This 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 dolutegravir (DTG) + a FDC containing emtricitabine/tenofovir alafenamide (F/TAF) 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 Dolutegravir + Emtricitabine/Tenofovir Alafenamide in HIV-1 Infected, Antiretroviral Treatment-Naive Adults

Conditions
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HIV-1 Infection

Intervention / Treatment
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* Drug: DTG
* Drug: F/TAF
* Drug: B/F/TAF
* Drug: DTG Placebo
* Drug: F/TAF 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 ≥ 30 mL per minute (min) (≥ 0.50 mL per second (sec)) according to the Cockcroft-Gault formula Key Exclusion Criteria: An opportunistic illness indicative of stage 3 HIV diagnosed within the 30 days prior to screening Decompensated cirrhosis (eg, 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 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 + DTG + F/TAF placebo administered without regard to food for at least 144 weeks. | Drug: B/F/TAF<br>* 50/200/25 milligrams (mg) FDC tablets administered orally, once daily<br>* Other names: Biktarvy®;Drug: DTG Placebo<br>* Tablets administered orally, once daily<br>Drug: F/TAF Placebo<br>* Tablets administered orally, once daily<br>|
| Active Comparator: DTG + F/TAF<br>DTG + F/TAF+ B/F/TAF placebo administered without regard to food for at least 144 weeks. | Drug: DTG<br>* 50 mg tablets administered orally, once daily<br>* Other names: Tivicay®;Drug: F/TAF<br>* 200/25 mg tablets administered orally, once daily<br>* Other names: Descovy®;Drug: B/F/TAF Placebo<br>* Tablets administered orally, once daily<br>|
| Experimental: Open-label Phase B/F/TAF from 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 milligrams (mg) FDC tablets administered orally, once daily<br>* Other names: Biktarvy®;|
| Experimental: Open-label Phase B/F/TAF from DTG + 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 milligrams (mg) FDC tablets administered orally, once daily<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 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 for the all B/F/TAF analysis. 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 nonmissing 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 for the all B/F/TAF analysis. 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 for the all B/F/TAF analysis. 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 nonmissing 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 for the all B/F/TAF analysis. 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