Clinical trial NCT02607956: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV-1 Infection
Keywords: HIV
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2015-11-18
Enrollment: 657
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants Who Achieved HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm
timeFrame: Week 48
Secondary outcomes:
measure: Percentage of Participants Who Achieved HIV-1 RNA < 50 Copies/mL at Week 96 as Defined by the US FDA-Defined Snapshot Algorithm
timeFrame: Week 96
measure: Percentage of Participants Who Achieved HIV-1 RNA < 50 Copies/mL at Week 144 as Defined by the US FDA-Defined Snapshot Algorithm
timeFrame: Week 144
measure: Percentage of Participants Who Achieved HIV-1 RNA < 20 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm
timeFrame: Week 48
measure: Percentage of Participants Who Achieved HIV-1 RNA < 20 Copies/mL at Week 96 as Defined by the US FDA-Defined Snapshot Algorithm
timeFrame: Week 96
measure: Percentage of Participants Who Achieved HIV-1 RNA < 20 Copies/mL at Week 144 as Defined by the US FDA-Defined Snapshot Algorithm
timeFrame: Week 144
measure: Change From Baseline in log10 HIV-1 RNA at Week 48
timeFrame: Baseline, Week 48
measure: Change From Baseline in log10 HIV-1 RNA at Week 96
timeFrame: Baseline, Week 96
measure: Change From Baseline in log10 HIV-1 RNA at Week 144
timeFrame: Baseline, Week 144
measure: Change From Baseline in CD4+ Cell Count at Week 48
timeFrame: Baseline, Week 48
measure: Change From Baseline in CD4+ Cell Count at Week 96
timeFrame: Baseline, Week 96
measure: Change From Baseline in CD4+ Cell Count at Week 144
timeFrame: Baseline, Week 144
measure: Percentage of Participants Who Achieved HIV-1 RNA < 50 Copies/mL at Week 48 Open-Label as Defined by Missing = Excluded Algorithm
timeFrame: Baseline, open-label Week 48
measure: Percentage of Participants Who Achieved HIV-1 RNA < 50 Copies/mL at Week 48 Open-Label as Defined by Missing = Failure Algorithm
timeFrame: Baseline, open-label Week 48
measure: Percentage of Participants Who Achieved HIV-1 RNA < 50 Copies/mL at Week 96 Open-Label as Defined by Missing = Excluded Algorithm
timeFrame: Baseline, open-label Week 96
measure: Percentage of Participants Who Achieved HIV-1 RNA < 50 Copies/mL at Week 96 Open-Label as Defined by Missing = Failure Algorithm
timeFrame: Baseline, open-label Week 96
measure: Change From Baseline in CD4+ Cell Count at Week 48 Open-Label
timeFrame: Baseline, open-label Week 48
measure: Change From Baseline in CD4+ Cell Count at Week 96 Open-Label
timeFrame: Baseline, open-label Week 96
Other outcomes:
Locations:
city: Phoenix
country: United States
state: Arizona
city: Phoenix
country: United States
state: Arizona
city: Beverly Hills
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Sacramento
country: United States
state: California
city: Sacramento
country: United States
state: California
city: San Francisco
country: United States
facility: Optimus Medical - ClinEdge - PPDS
state: California
city: San Leandro
country: United States
facility: Kaiser Permanente
state: California
city: Denver
country: United States
state: Colorado
city: Washington
country: United States
state: District of Columbia
city: Washington
country: United States
state: District of Columbia
city: Washington
country: United States
state: District of Columbia
city: DeLand
country: United States
state: Florida
city: Fort Lauderdale
country: United States
state: Florida
city: Fort Pierce
country: United States
state: Florida
city: Miami Beach
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Oakland Park
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Pensacola
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: West Palm Beach
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Atlanta
country: United States
state: Georgia
city: Decatur
country: United States
state: Georgia
city: Macon
country: United States
state: Georgia
city: Savannah
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Chicago
country: United States
state: Illinois
city: Indianapolis
country: United States
state: Indiana
city: Baltimore
country: United States
facility: Sinai Hospital of Baltimore
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Boston
country: United States
state: Massachusetts
city: Springfield
country: United States
state: Massachusetts
city: Berkley
country: United States
state: Michigan
city: Detroit
country: United States
state: Michigan
city: Kansas City
country: United States
state: Missouri
city: Saint Louis
country: United States
state: Missouri
city: Saint Louis
country: United States
state: Missouri
city: Hillsborough
country: United States
state: New Jersey
city: Newark
country: United States
state: New Jersey
city: Albany
country: United States
state: New York
city: Bronx
country: United States
state: New York
city: Manhasset
country: United States
state: New York
city: New York
country: United States
state: New York
city: New York
country: United States
state: New York
city: Chapel Hill
country: United States
state: North Carolina
city: Charlotte
country: United States
state: North Carolina
city: Greensboro
country: United States
facility: Cone Health Regional Center for Infectious Disease
state: North Carolina
city: Greenville
country: United States
state: North Carolina
city: Huntersville
country: United States
state: North Carolina
city: Winston-Salem
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Philadelphia
country: United States
state: Pennsylvania
city: Philadelphia
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny Health Network
state: Pennsylvania
city: Columbia
country: United States
state: South Carolina
city: Austin
country: United States
state: Texas
city: Bellaire
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Dallas
country: United States
facility: AIDS Arms Inc
state: Texas
city: Dallas
country: United States
state: Texas
city: Dallas
country: United States
facility: North Texas Infectious Diseases Consultants PA
state: Texas
city: Fort Worth
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Longview
country: United States
state: Texas
city: Annandale
country: United States
state: Virginia
city: Seattle
country: United States
state: Washington
city: Spokane
country: United States
state: Washington
city: Sydney
country: Australia
state: New South Wales
city: Carlton
country: Australia
state: Victoria
city: Clayton
country: Australia
state: Victoria
city: Melbourne
country: Australia
state: Victoria
city: Prahran
country: Australia
state: Victoria
city: Prahran
country: Australia
facility: Prahran Market Clinic
state: Victoria
city: Antwerp
country: Belgium
city: Ghent
country: Belgium
city: Montreal
country: Canada
facility: McGill University Health Center
city: Ottawa
country: Canada
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
city: Toronto
country: Canada
city: Toronto
country: Canada
city: Winnipeg
country: Canada
city: Santo Domingo
country: Dominican Republic
city: Montpellier
country: France
city: Nice
country: France
facility: CHU de Nice Archet I
city: Tourcoing
country: France
city: Tourcoing
country: France
city: Berlin
country: Germany
city: Düsseldorf
country: Germany
city: Essen
country: Germany
city: Frankfurt
country: Germany
city: Frankfurt
country: Germany
city: Hamburg
country: Germany
city: Köln
country: Germany
facility: Uniklinik Köln
city: München
country: Germany
city: Bergamo
country: Italy
city: Milano
country: Italy
city: Roma
country: Italy
city: San Juan
country: Puerto Rico
city: San Juan
country: Puerto Rico
city: Alicante
country: Spain
city: Badalona
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Malaga
country: Spain
city: Vigo
country: Spain
city: Birmingham
country: United Kingdom
city: Birmingham
country: United Kingdom
city: London
country: United Kingdom
city: London
country: United Kingdom
city: London
country: United Kingdom
city: London
country: United Kingdom
city: London
country: United Kingdom
facility: Chelsea and Westminster NHS Trust
city: London
country: United Kingdom
facility: St George's Healthcare NHS Trust
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
city: Manchester
country: United Kingdom
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: Sax PE, Pozniak A, Montes ML, Koenig E, DeJesus E, Stellbrink HJ, Antinori A, Workowski K, Slim J, Reynes J, Garner W, Custodio J, White K, SenGupta D, Cheng A, Quirk E. Coformulated bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir with emtricitabine and tenofovir alafenamide, for initial treatment of HIV-1 infection (GS-US-380-1490): a randomised, double-blind, multicentre, phase 3, non-inferiority trial. Lancet. 2017 Nov 4;390(10107):2073-2082. doi: 10.1016/S0140-6736(17)32340-1. Epub 2017 Aug 31.
citation: Gupta SK, Post FA, Arribas JR, Eron JJ Jr, Wohl DA, Clarke AE, Sax PE, Stellbrink HJ, Esser S, Pozniak AL, Podzamczer D, Waters L, Orkin C, Rockstroh JK, Mudrikova T, Negredo E, Elion RA, Guo S, Zhong L, Carter C, Martin H, Brainard D, SenGupta D, Das M. Renal safety of tenofovir alafenamide vs. tenofovir disoproxil fumarate: a pooled analysis of 26 clinical trials. AIDS. 2019 Jul 15;33(9):1455-1465. doi: 10.1097/QAD.0000000000002223.
citation: Stellbrink HJ, Arribas JR, Stephens JL, Albrecht H, Sax PE, Maggiolo F, Creticos C, Martorell CT, Wei X, Acosta R, Collins SE, Brainard D, Martin H. Co-formulated bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir with emtricitabine and tenofovir alafenamide for initial treatment of HIV-1 infection: week 96 results from a randomised, double-blind, multicentre, phase 3, non-inferiority trial. Lancet HIV. 2019 Jun;6(6):e364-e372. doi: 10.1016/S2352-3018(19)30080-3. Epub 2019 May 5.
citation: Acosta RK, Willkom M, Martin R, Chang S, Wei X, Garner W, Lutz J, Majeed S, SenGupta D, Martin H, Quirk E, White KL. Resistance Analysis of Bictegravir-Emtricitabine-Tenofovir Alafenamide in HIV-1 Treatment-Naive Patients through 48 Weeks. Antimicrob Agents Chemother. 2019 Apr 25;63(5):e02533-18. doi: 10.1128/AAC.02533-18. Print 2019 May.
citation: Acosta R, Willkom M, Martin R, Chang S, Liu X, Hedskog C, et al. Low-frequency resistance variants in ART-naive participants do not affect bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) triple therapy outcome. [Poster MOPEB242]. 10th IAS Conference on HIV Science (IAS 2019); 2019 July 21-24; Mexico City, Mexico.
citation: Johnson M, Taylor S, Wei X, Collins SE, Martin H. Hepatic Safety of Bictegravir/Emtricitabine/Tenofovir Alafenamide [Poster P061]. 25th Annual Conference of the British HIV Association; 2019 02-05 April; Bournemouth, United Kingdom.
citation: Gupta S, Mills A, Brinson C, Workowski K, Clarke A, Antinori A, et al. 96 Week Efficacy and Safety of B/F/TAF in Treatment-Naïve Adults and Adults ≥50 Years [Poster 502]. CROI 2019; 2019 04-07 March; Seattle, WA.
citation: Acosta R, White K, Garner W, Wei X, Andreatta K, Willkom M, et al. HIV-1 subtype (B or non-B) had no impact on the efficacy of B/F/TAF or resistance development in five phase 3 treatment-naïve or switch studies. [Poster THPEB077]. 22nd International AIDS Conference; 2018 July 23-27; Amsterdam, Netherlands.
citation: White K, Kulkarni R, Willkom M, Martin R, Chang S, Wei X, et al. Pooled week 48 efficacy and baseline resistance: B/F/TAF in treatment-naive patients. [Poster 532]. Conference on Retroviruses and Opportunistic Infections; 2018 March 4-7; Boston, USA.
citation: Wohl D, Clarke A, Maggiolo F, Garner W, Laouri M, Martin H, Quirk E. Patient-Reported Symptoms Over 48 Weeks Among Participants in Randomized, Double-Blind, Phase III Non-inferiority Trials of Adults with HIV on Co-formulated Bictegravir, Emtricitabine, and Tenofovir Alafenamide versus Co-formulated Abacavir, Dolutegravir, and Lamivudine. Patient. 2018 Oct;11(5):561-573. doi: 10.1007/s40271-018-0322-8.
citation: Wohl DA, Yazdanpanah Y, Baumgarten A, Clarke A, Thompson MA, Brinson C, Hagins D, Ramgopal MN, Antinori A, Wei X, Acosta R, Collins SE, Brainard D, Martin H. Bictegravir combined with emtricitabine and tenofovir alafenamide versus dolutegravir, abacavir, and lamivudine for initial treatment of HIV-1 infection: week 96 results from a randomised, double-blind, multicentre, phase 3, non-inferiority trial. Lancet HIV. 2019 Jun;6(6):e355-e363. doi: 10.1016/S2352-3018(19)30077-3. Epub 2019 May 5.
citation: Acosta R, Andreatta K, D'Antoni M, Collins S, Martin H, White K. HIV Viral Blips in Adults Treated with INSTI-Based Regimens Through 144 Weeks. [Poster 540]. Conference on Retroviruses and Opportunistic Infections 2020 (CROI 2020); 2020 March 8-11; Boston, Massachusetts.
citation: Mills A, Gupta SK, Brinson C, Workowski K, Clarke A, Antinori A, Stephens JL, et al. 144-Week Efficacy and Safety of B/F/TAF in Treatment-Naive Adults Age ≥50 Years. [Poster 477]. Conference on Retroviruses and Opportunistic Infections 2020 (CROI 2020); 2020 March 8-11; Boston, Massachusetts.
citation: Orkin C, DeJesus E, Sax PE, Arribas JR, Gupta SK, Martorell C, Stephens JL, Stellbrink HJ, Wohl D, Maggiolo F, Thompson MA, Podzamczer D, Hagins D, Flamm JA, Brinson C, Clarke A, Huang H, Acosta R, Brainard DM, Collins SE, Martin H; GS-US-380-1489; GS-US-380-1490 study investigators. Fixed-dose combination bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir-containing regimens for initial treatment of HIV-1 infection: week 144 results from two randomised, double-blind, multicentre, phase 3, non-inferiority trials. Lancet HIV. 2020 Jun;7(6):e389-e400. doi: 10.1016/S2352-3018(20)30099-0.
citation: Ramgopal M, Maggiolo F, Ward D, Leboucche B, Rizzardini G, Molina JM, et al. Pooled Analysis of 4 International Trials of Bictegravir/Emtrictabine/Tenofovir Alafenamide (B/F/TAF) in Adults Aged ≥ 65 Years Demonstrating Safety and Efficacy: Week 48 Results. [Oral OAB0403].AIDS 2020; 2020 July 6-10; Virtual.
citation: Acosta R, Andreatta K, D'Antoni M, Collins S, Martin H, White K. Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) shows high efficacy in clinical study participants infected with HIV-1 subtype F. [Poster P124]. HIV Drug Therapy 2020 (HIV Glasgow 2020); 2020 October 5-8; Glasgow, United Kingdom.
citation: Acosta R, Chen G, Chang S, Martin R, Wang X, Huang H, et al. HIV with Transmitted Drug Resistance Is Durably Suppressed by B/F/TAF at Week 144. [Poster 430]. Conference on Retroviruses and Opportunistic Infections 2021 (CROI 2021); 2021 June 3-November 3; Virtual.
citation: Acosta RK, Chen GQ, Chang S, Martin R, Wang X, Huang H, Brainard D, Collins SE, Martin H, White KL. Three-year study of pre-existing drug resistance substitutions and efficacy of bictegravir/emtricitabine/tenofovir alafenamide in HIV-1 treatment-naive participants. J Antimicrob Chemother. 2021 Jul 15;76(8):2153-2157. doi: 10.1093/jac/dkab115.
citation: Workowski K, Orkin C, Sax P, Hagins D, Koenig E, Stephens JL, et al. Four-Year Outcomes of B/F/TAF in Treatment-Naïve Adults [Poster 415]. Conference on Retroviruses and Opportunistic Infections 2021 (CROI 2021); 2021 June 3-November 3; Virtual.
citation: Acosta R, Chen G, Qin L, Wang X, Huang H, Hindman J, et al. Achievement of Undetectable HIV-1 RNA in the B/F/TAF Treatment-Naive Clinical Trials. [Poster PEB150]. 11th IAS Conference on HIV Science (IAS 2021); 2021 July 18-21; Virtual.
citation: Acosta R, Chen G, Huang H, Liu H, White K. Unreturned Pill Bottles in the 1489 and 1490 Clinical Trials: An Important Measure of Poor Adherence That Is Often Ignored in Pill Count Calculations. [Poster 902]. IDWeek 2021; 2021 September 29-October 3; Virtual.
citation: Arribas J, Orkin C, Maggiolo F, Antinori A, Lazzarin A, Yasdanpanah, et al. Long-term Analysis of B/F/TAF in Treatment-Naïve Adults Living With HIV Through Four Years of Follow-up. [PEB151]. 11th IAS Conference on HIV Science (IAS 2021); 2021 July 18-21; Virtual.
citation: Daar E, Orkin C, Sax P, Stephens J, Koenig E, Clarke A, et al. Incidence of Metabolic Complications Among Treatment-naïve Adults Living With HIV-1 Randomized to B/F/TAF, DTG/ABC/3TC or DTG+F/TAF After 3 Years. [Oral 69]. IDWeek 2021; 2021 September 29- October 3; Virtual.
citation: Pozniak A, et al. Outcomes 48 Weeks After Switching From DTG/ABC/3TC or DTG+F/TAF to B/F/TAF. [PE2/68]. 18th European AIDS Conference (EAC 2021), 2021 October 27-30; London, United Kingdom.