Safety and Efficacy of Bictegravir + Emtricitabine/Tenofovir Alafenamide Versus Dolutegravir + Emtricitabine/Tenofovir Alafenamide in HIV-1 Infected, Antiretroviral Treatment-Naive Adults
Phase 2
Completed
- Conditions
- HIV-1 Infection
- Interventions
- Registration Number
- NCT02397694
- Lead Sponsor
- Gilead Sciences
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 98
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description BIC + F/TAF BIC 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. BIC + F/TAF DTG Placebo 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. DTG + F/TAF DTG 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. BIC + F/TAF B/F/TAF 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. DTG + F/TAF F/TAF 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. DTG + F/TAF BIC Placebo 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. DTG + F/TAF B/F/TAF 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. Open Label Extension Phase B/F/TAF 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. BIC + F/TAF F/TAF 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.
- Primary Outcome Measures
Name Time Method Percentage of Participants With HIV-1 RNA < 50 Copies/mL as Determined by the FDA-defined Snapshot Algorithm. Week 24 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.
- Secondary Outcome Measures
Name Time Method PK Parameter: Cmax for Bictegravir (BIC), Emtricitabine (FTC), Tenofovir Alafenamide (TAF) and Tenofavir (TFV) at Steady-State 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours postdose at Week 4 or 8 Cmax is the maximum observed plasma concentration of the drug.
PK Parameter: Tmax for BIC, FTC, TAF, and TFV at Steady-State 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours postdose at Week 4 or 8 Tmax was defined as the time to Cmax.
PK Parameter:Ctau for BIC, FTC and TFV 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours postdose at Week 4 or 8 Ctau was defined as the observed drug concentration at the end of the dosing interval.
PK Parameter: AUCtau for BIC, FTC, TAF, and TFV 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours postdose at Week 4 or 8 AUCtau is defined as the area under the concentration-time curve of the drug over time.
PK Parameter: t1/2 of BIC, FTC, TAF, and TFV 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours postdose at Week 4 or 8 t1/2 was defined as the terminal elimination half-life of the drug
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) Percentage of Participants With HIV-1 RNA < 50 Copies/mL as Determined by the FDA-defined Snapshot Algorithm at Week 48 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.
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 log10 HIV-1 RNA at Week 12 Baseline; Week 12 Percentage of Participants With HIV-1 RNA < 50 Copies/mL as Determined by the FDA-defined Snapshot Algorithm at Week 12 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.
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