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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

Phase 3
Completed
Conditions
HIV-1 Infection
Interventions
Drug: B/F/TAF
Drug: DTG Placebo
Drug: F/TAF Placebo
Drug: B/F/TAF Placebo
Registration Number
NCT02607956
Lead Sponsor
Gilead Sciences
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
657
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
B/F/TAFB/F/TAFB/F/TAF + DTG + F/TAF placebo administered without regard to food for at least 144 weeks.
B/F/TAFDTG PlaceboB/F/TAF + DTG + F/TAF placebo administered without regard to food for at least 144 weeks.
B/F/TAFF/TAF PlaceboB/F/TAF + DTG + F/TAF placebo administered without regard to food for at least 144 weeks.
DTG + F/TAFF/TAFDTG + F/TAF+ B/F/TAF placebo administered without regard to food for at least 144 weeks.
DTG + F/TAFB/F/TAF PlaceboDTG + F/TAF+ B/F/TAF placebo administered without regard to food for at least 144 weeks.
Open-label Phase B/F/TAF from B/F/TAFB/F/TAFAfter 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.
Open-label Phase B/F/TAF from DTG + F/TAFB/F/TAFAfter 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.
DTG + F/TAFDTGDTG + F/TAF+ B/F/TAF placebo administered without regard to food for at least 144 weeks.
Primary Outcome Measures
NameTimeMethod
Percentage of Participants Who Achieved HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot AlgorithmWeek 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.

Secondary Outcome Measures
NameTimeMethod
Percentage of Participants Who Achieved HIV-1 RNA < 20 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot AlgorithmWeek 48

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.

Percentage of Participants Who Achieved HIV-1 RNA < 20 Copies/mL at Week 96 as Defined by the US FDA-Defined Snapshot AlgorithmWeek 96

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.

Change From Baseline in log10 HIV-1 RNA at Week 96Baseline, Week 96
Percentage of Participants Who Achieved HIV-1 RNA < 20 Copies/mL at Week 144 as Defined by the US FDA-Defined Snapshot AlgorithmWeek 144

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.

Change From Baseline in log10 HIV-1 RNA at Week 48Baseline, Week 48
Change From Baseline in log10 HIV-1 RNA at Week 144Baseline, Week 144
Percentage of Participants Who Achieved HIV-1 RNA < 50 Copies/mL at Week 144 as Defined by the US FDA-Defined Snapshot AlgorithmWeek 144

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.

Percentage of Participants Who Achieved HIV-1 RNA < 50 Copies/mL at Week 96 as Defined by the US FDA-Defined Snapshot AlgorithmWeek 96

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.

Change From Baseline in CD4+ Cell Count at Week 48Baseline, Week 48
Change From Baseline in CD4+ Cell Count at Week 96Baseline, Week 96
Change From Baseline in CD4+ Cell Count at Week 144Baseline, Week 144
Percentage of Participants Who Achieved HIV-1 RNA < 50 Copies/mL at Week 48 Open-Label as Defined by Missing = Excluded AlgorithmBaseline, open-label Week 48

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.

Percentage of Participants Who Achieved HIV-1 RNA < 50 Copies/mL at Week 48 Open-Label as Defined by Missing = Failure AlgorithmBaseline, open-label Week 48

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.

Percentage of Participants Who Achieved HIV-1 RNA < 50 Copies/mL at Week 96 Open-Label as Defined by Missing = Excluded AlgorithmBaseline, open-label Week 96

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.

Percentage of Participants Who Achieved HIV-1 RNA < 50 Copies/mL at Week 96 Open-Label as Defined by Missing = Failure AlgorithmBaseline, open-label Week 96

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.

Change From Baseline in CD4+ Cell Count at Week 48 Open-LabelBaseline, open-label Week 48
Change From Baseline in CD4+ Cell Count at Week 96 Open-LabelBaseline, open-label Week 96

Trial Locations

Locations (15)

St George's Healthcare NHS Trust

🇬🇧

London, United Kingdom

Sunnybrook Health Sciences Centre

🇨🇦

Toronto, Canada

Prahran Market Clinic

🇦🇺

Prahran, Victoria, Australia

Chelsea and Westminster NHS Trust

🇬🇧

London, United Kingdom

McGill University Health Center

🇨🇦

Montreal, Canada

CHU de Nice Archet I

🇫🇷

Nice, France

Uniklinik Köln

🇩🇪

Köln, Germany

Optimus Medical - ClinEdge - PPDS

🇺🇸

San Francisco, California, United States

Kaiser Permanente

🇺🇸

San Leandro, California, United States

Cone Health Regional Center for Infectious Disease

🇺🇸

Greensboro, North Carolina, United States

Allegheny Health Network

🇺🇸

Pittsburgh, Pennsylvania, United States

AIDS Arms Inc

🇺🇸

Dallas, Texas, United States

North Texas Infectious Diseases Consultants PA

🇺🇸

Dallas, Texas, United States

Sinai Hospital of Baltimore

🇺🇸

Baltimore, Maryland, United States

Hospital Universitario Ramon y Cajal

🇪🇸

Madrid, Spain

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