Safety and Efficacy of Bictegravir + Emtricitabine/Tenofovir Alafenamide Versus Dolutegravir + Emtricitabine/Tenofovir Alafenamide in HIV-1 Infected, Antiretroviral Treatment-Naive Adults

Study Overview
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Brief Summary
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This study will evaluate the efficacy, safety and tolerability of bictegravir (BIC) + emtricitabine/tenofovir alafenamide (F/TAF) fixed dose combination (FDC) versus dolutegravir (DTG) + F/TAF in HIV-1 Infected, antiretroviral treatment-naive adults. This study will also evaluate the pharmacokinetic (PK) profile of BIC, emtricitabine and TAF.

Official Title
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A Phase 2, Randomized, Double-Blinded Study of 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: BIC
* Drug: F/TAF
* Drug: DTG
* Drug: BIC Placebo
* Drug: DTG Placebo
* Drug: B/F/TAF


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Antiretroviral naive (≤ 10 days of prior therapy with any antiretroviral agent) Plasma HIV-1 RNA levels ≥ 1,000 copies/mL at screening Screening genotype report provided by Gilead Sciences must show sensitivity to tenofovir (TFV) and emtricitabine (FTC) Adequate renal function as measured by estimated glomerular filtration rate ≥ 70 mL/min according to the Cockcroft-Gault formula CD4+ cell count ≥ 200 cells/µL at screening Key Exclusion Criteria: A new AIDS-defining condition diagnosed within the 30 days prior to screening as defined in the study protocol Prior use of antiretrovirals in the setting of pre-exposure prophylaxis (PrEP) or post exposure prophylaxis (PEP) Chronic hepatitis B virus (HBV) infection Hepatitis C infection (Individuals who are hepatitis C virus (HCV) Ab positive, but have a documented negative HCV RNA, are eligible) Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to baseline Participation in any other clinical trial 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: BIC + F/TAF<br>Participants will receive BIC + F/TAF FDC + DTG placebo for 48 weeks. Following Week 48, participants will continue to take their blinded treatment and attend visits every 12 weeks until treatment assignments have been unblinded. Participants will return for an unblinding visit and be given the option to participate in an open-label rollover extension and receive bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) until it becomes commercially available, or until Gilead Sciences elects to terminate the development of BIC/F/TAF. | Drug: BIC<br>* 75 mg tablet administered orally once daily<br>* Other names: GS-9883;Drug: F/TAF<br>* 200/25 mg FDC tablet administered orally once daily<br>Drug: DTG Placebo<br>* Tablet administered orally once daily<br>Drug: B/F/TAF<br>* 50/200/25 mg FDC tablet administered orally once daily<br>|
| Active Comparator: DTG + F/TAF<br>Participants will receive DTG + F/TAF FDC + BIC placebo for 48 weeks. Following Week 48, participants will continue to take their blinded treatment and attend visits every 12 weeks until treatment assignments have been unblinded. Participants will return for an unblinding visit and be given the option to participate in an open-label rollover extension and receive B/F/TAF until it becomes commercially available, or until Gilead Sciences elects to terminate the development of BIC/F/TAF. | Drug: F/TAF<br>* 200/25 mg FDC tablet administered orally once daily<br>Drug: DTG<br>* 50 mg tablet administered orally once daily<br>* Other names: Tivicay®;Drug: BIC Placebo<br>* Tablet administered orally once daily<br>Drug: B/F/TAF<br>* 50/200/25 mg FDC tablet administered orally once daily<br>|
| Experimental: Open Label Extension Phase<br>After Week 48 participants continued to take their randomized study drug and attended visits every 12 weeks until treatment assignments were unblinded, at which point all participants returned for an unblinding visit and were given the option to participate in an open-label rollover extension to receive an FDC containing B/F/TAF. | Drug: B/F/TAF<br>* 50/200/25 mg FDC tablet administered orally once daily<br>|

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 as Determined by the FDA-defined Snapshot Algorithm. | The percentage of participants achieving HIV-1 RNA < 50 copies/mL at Week 24 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 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL as Determined by the FDA-defined Snapshot Algorithm at Week 12 | The percentage of participants achieving HIV-1 RNA < 50 copies/mL at Week 12 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 12 | 
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL as Determined by the FDA-defined Snapshot Algorithm at 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. | Week 48 | 
| The Change From Baseline in log10 HIV-1 RNA at Week 12 |  | Baseline; Week 12 | 
| The Change From Baseline in log10 HIV-1 RNA at Week 24 |  | Baseline; Week 24 | 
| The Change From Baseline in log10 HIV-1 RNA at Week 48 |  | Baseline; Week 48 | 
| The Change From Baseline in Cluster of Differentiation 4 Positive (CD4+) Cell Count at Week 12 |  | Baseline; Week 12 | 
| The Change From Baseline in CD4+ Cell Count at Week 24 |  | Baseline; Week 24 | 
| The Change From Baseline in CD4+ Cell Count at Week 48 |  | Baseline; Week 48 | 
| Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) During Double-Blinded Randomized Phase |  | First dose date up to last dose (maximum duration: 58 Weeks) plus 30 days (During Double-Blinded Randomized Phase) | 
| Percentage of Participants With Treatment Emergent Laboratory Abnormalities During Double-Blind Randomized Phase |  | First dose date up to last dose (maximum duration: 58 Weeks) plus 30 days (During Double-Blinded Randomized Phase) | 
| PK Parameter: Cmax for Bictegravir (BIC), Emtricitabine (FTC), Tenofovir Alafenamide (TAF) and Tenofavir (TFV) at Steady-State | Cmax is the maximum observed plasma concentration of the drug. | 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours postdose at Week 4 or 8 | 
| PK Parameter: Tmax for BIC, FTC, TAF, and TFV at Steady-State | Tmax was defined as the time to Cmax. | 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours postdose at Week 4 or 8 | 
| PK Parameter:Ctau for BIC, FTC and TFV | Ctau was defined as the observed drug concentration at the end of the dosing interval. | 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours postdose at Week 4 or 8 | 
| PK Parameter: AUCtau for BIC, FTC, TAF, and TFV | AUCtau is defined as the area under the concentration-time curve of the drug over time. | 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours postdose at Week 4 or 8 | 
| PK Parameter: t1/2 of BIC, FTC, TAF, and TFV | t1/2 was defined as the terminal elimination half-life of the drug | 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours postdose at Week 4 or 8 | 

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