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

NCT ID: NCT02607956

Last Updated: 2022-03-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 657 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-11-11
• Study Completion Date: 2021-07-05

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.

Conditions

HIV-1 Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

B/F/TAF

B/F/TAF + DTG + F/TAF placebo administered without regard to food for at least 144 weeks.

Group Type: EXPERIMENTAL

B/F/TAF

Intervention Type: DRUG

50/200/25 milligrams (mg) FDC tablets administered orally, once daily

DTG Placebo

Intervention Type: DRUG

Tablets administered orally, once daily

F/TAF Placebo

Intervention Type: DRUG

Tablets administered orally, once daily

DTG + F/TAF

DTG + F/TAF+ B/F/TAF placebo administered without regard to food for at least 144 weeks.

Group Type: ACTIVE_COMPARATOR

DTG

Intervention Type: DRUG

50 mg tablets administered orally, once daily

F/TAF

Intervention Type: DRUG

200/25 mg tablets administered orally, once daily

B/F/TAF Placebo

Intervention Type: DRUG

Tablets administered orally, once daily

Open-label Phase B/F/TAF from B/F/TAF

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.

Group Type: EXPERIMENTAL

B/F/TAF

Intervention Type: DRUG

50/200/25 milligrams (mg) FDC tablets administered orally, once daily

Open-label Phase B/F/TAF from DTG + F/TAF

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.

Group Type: EXPERIMENTAL

B/F/TAF

Intervention Type: DRUG

50/200/25 milligrams (mg) FDC tablets administered orally, once daily

Interventions

DTG

50 mg tablets administered orally, once daily

Intervention Type: DRUG

F/TAF

200/25 mg tablets administered orally, once daily

Intervention Type: DRUG

B/F/TAF

50/200/25 milligrams (mg) FDC tablets administered orally, once daily

Intervention Type: DRUG

DTG Placebo

Tablets administered orally, once daily

Intervention Type: DRUG

F/TAF Placebo

Tablets administered orally, once daily

Intervention Type: DRUG

B/F/TAF Placebo

Tablets administered orally, once daily

Intervention Type: DRUG

Other Intervention Names

Tivicay®; Descovy®; GS-9883/F/TAF; Biktarvy®

Eligibility Criteria

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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

Phoenix, Arizona, United States

Phoenix, Arizona, United States

Beverly Hills, California, United States

Los Angeles, California, United States

Los Angeles, California, United States

Los Angeles, California, United States

Los Angeles, California, United States

Sacramento, California, United States

Sacramento, California, United States

Optimus Medical - ClinEdge - PPDS

San Francisco, California, United States

Kaiser Permanente

San Leandro, California, United States

Denver, Colorado, United States

Washington D.C., District of Columbia, United States

Washington D.C., District of Columbia, United States

Washington D.C., District of Columbia, United States

DeLand, Florida, United States

Fort Lauderdale, Florida, United States

Ft. Pierce, Florida, United States

Miami, Florida, United States

Miami, Florida, United States

Miami Beach, Florida, United States

Oakland Park, Florida, United States

Orlando, Florida, United States

Pensacola, Florida, United States

Tampa, Florida, United States

West Palm Beach, Florida, United States

Atlanta, Georgia, United States

Atlanta, Georgia, United States

Decatur, Georgia, United States

Macon, Georgia, United States

Savannah, Georgia, United States

Chicago, Illinois, United States

Chicago, Illinois, United States

Indianapolis, Indiana, United States

Sinai Hospital of Baltimore

Baltimore, Maryland, United States

Boston, Massachusetts, United States

Boston, Massachusetts, United States

Springfield, Massachusetts, United States

Berkley, Michigan, United States

Detroit, Michigan, United States

Kansas City, Missouri, United States

St Louis, Missouri, United States

St Louis, Missouri, United States

Hillsborough, New Jersey, United States

Newark, New Jersey, United States

Albany, New York, United States

Manhasset, New York, United States

New York, New York, United States

New York, New York, United States

The Bronx, New York, United States

Chapel Hill, North Carolina, United States

Charlotte, North Carolina, United States

Cone Health Regional Center for Infectious Disease

Greensboro, North Carolina, United States

Greenville, North Carolina, United States

Huntersville, North Carolina, United States

Winston-Salem, North Carolina, United States

Cincinnati, Ohio, United States

Philadelphia, Pennsylvania, United States

Philadelphia, Pennsylvania, United States

Allegheny Health Network

Pittsburgh, Pennsylvania, United States

Columbia, South Carolina, United States

Austin, Texas, United States

Bellaire, Texas, United States

Dallas, Texas, United States

AIDS Arms Inc

Dallas, Texas, United States

Dallas, Texas, United States

North Texas Infectious Diseases Consultants PA

Dallas, Texas, United States

Fort Worth, Texas, United States

Houston, Texas, United States

Houston, Texas, United States

Longview, Texas, United States

Annandale, Virginia, United States

Seattle, Washington, United States

Spokane, Washington, United States

Sydney, New South Wales, Australia

Carlton, Victoria, Australia

Clayton, Victoria, Australia

Melbourne, Victoria, Australia

Prahran, Victoria, Australia

Prahran Market Clinic

Prahran, Victoria, Australia

Antwerp, , Belgium

Ghent, , Belgium

McGill University Health Center

Montreal, , Canada

Ottawa, , Canada

Sunnybrook Health Sciences Centre

Toronto, , Canada

Toronto, , Canada

Toronto, , Canada

Winnipeg, , Canada

Santo Domingo, , Dominican Republic

Montpellier, , France

CHU de Nice Archet I

Nice, , France

Tourcoing, , France

Tourcoing, , France

Berlin, , Germany

Uniklinik Köln

Cologne, , Germany

Düsseldorf, , Germany

Essen, , Germany

Frankfurt, , Germany

Frankfurt, , Germany

Hamburg, , Germany

München, , Germany

Bergamo, , Italy

Milan, , Italy

Roma, , Italy

San Juan, , Puerto Rico

San Juan, , Puerto Rico

Alicante, , Spain

Badalona, , Spain

Madrid, , Spain

Hospital Universitario Ramon y Cajal

Madrid, , Spain

Madrid, , Spain

Madrid, , Spain

Málaga, , Spain

Vigo, , Spain

Birmingham, , United Kingdom

Birmingham, , United Kingdom

London, , United Kingdom

London, , United Kingdom

London, , United Kingdom

London, , United Kingdom

Chelsea and Westminster NHS Trust

London, , United Kingdom

St George's Healthcare NHS Trust

London, , United Kingdom

London, , United Kingdom

Manchester, , United Kingdom

Manchester, , United Kingdom

Countries

United States; Australia; Belgium; Canada; Dominican Republic; France; Germany; Italy; Puerto Rico; Spain; United Kingdom

References

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.

Reference Type: RESULT

PMID: 28867499 (View on PubMed)

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.

Reference Type: RESULT

PMID: 30932951 (View on PubMed)

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.

Reference Type: RESULT

PMID: 31068272 (View on PubMed)

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.

Reference Type: RESULT

PMID: 30803969 (View on PubMed)

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.

Reference Type: RESULT

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.

Reference Type: RESULT

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.

Reference Type: RESULT

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.

Reference Type: RESULT

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.

Reference Type: RESULT

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.

Reference Type: RESULT

PMID: 29956087 (View on PubMed)

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.

Reference Type: RESULT

PMID: 31068270 (View on PubMed)

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.

Reference Type: RESULT

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.

Reference Type: RESULT

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.

Reference Type: RESULT

PMID: 32504574 (View on PubMed)

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.

Reference Type: RESULT

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.

Reference Type: RESULT

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.

Reference Type: RESULT

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.

Reference Type: RESULT

PMID: 33880558 (View on PubMed)

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.

Reference Type: RESULT

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.

Reference Type: RESULT

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.

Reference Type: RESULT

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.

Reference Type: RESULT

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.

Reference Type: RESULT

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.

Reference Type: RESULT

Sax PE, Hindman JT, Martin H, Wohl D. Two 5-year studies of bictegravir/emtricitabine/tenofovir alafenamide in people with HIV: a plain-language summary. Future Microbiol. 2024;19(14):1185-1193. doi: 10.1080/17460913.2024.2372231. Epub 2024 Sep 4.

Reference Type: DERIVED

PMID: 39229805 (View on PubMed)

Orkin C, Antinori A, Rockstroh JK, Moreno-Guillen S, Martorell CT, Molina JM, Lazzarin A, Maggiolo F, Yazdanpanah Y, Andreatta K, Huang H, Hindman JT, Martin H, Pozniak A. Switch to bictegravir/emtricitabine/tenofovir alafenamide from dolutegravir-based therapy. AIDS. 2024 Jun 1;38(7):983-991. doi: 10.1097/QAD.0000000000003865. Epub 2024 Feb 21.

Reference Type: DERIVED

PMID: 38349226 (View on PubMed)

Sax PE, Arribas JR, Orkin C, Lazzarin A, Pozniak A, DeJesus E, Maggiolo F, Stellbrink HJ, Yazdanpanah Y, Acosta R, Huang H, Hindman JT, Martin H, Baeten JM, Wohl D; GS-US-380-1489 and GS-US-380-1490 study investigators. Bictegravir/emtricitabine/tenofovir alafenamide as initial treatment for HIV-1: five-year follow-up from two randomized trials. EClinicalMedicine. 2023 May 11;59:101991. doi: 10.1016/j.eclinm.2023.101991. eCollection 2023 May.

Reference Type: DERIVED

PMID: 37200995 (View on PubMed)

Provided Documents

Document Type: Study Protocol: Original

View Document

Document Type: Study Protocol: Amendment 1

View Document

Document Type: Study Protocol: Amendment 2

View Document

Document Type: Study Protocol: Amendment 3

View Document

Document Type: Statistical Analysis Plan: Original

View Document

Document Type: Statistical Analysis Plan: Amendment 1

View Document

Document Type: Statistical Analysis Plan: Final Analysis

View Document

Other Identifiers

2015-003988-10

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GS-US-380-1490

Identifier Type: -

Identifier Source: org_study_id