Study to Evaluate the Safety and Efficacy of Bictegravir/Emtricitabine/Tenofovir Alafenamide Versus Abacavir/Dolutegravir/Lamivudine in Human Immunodeficiency Virus-1 (HIV-1) Infected, Antiretroviral Treatment-Naive Adults

HIV-1 Infection Clinical Trial

Official title:

A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of GS-9883/Emtricitabine/Tenofovir Alafenamide Versus Abacavir/Dolutegravir/Lamivudine in HIV-1 Infected, Antiretroviral Treatment-Naive Adults

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02607930
• Other study ID #: GS-US-380-1489
• Secondary ID: 2015-004024-54
• Status: Completed
• Phase: Phase 3
• Start date: November 13, 2015
• Est. completion date: July 2, 2021

Study information

• Verified date: February 2022
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The 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 a FDC containing abacavir/dolutegravir/lamivudine (ABC/DTG/3TC) in HIV-1 infected, antiretroviral treatment naive-adults.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 631
• Est. completion date: July 2, 2021
• Est. primary completion date: May 9, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 = 50 milliliter per minute (mL/min) (= 0.83 milliliter per second [mL/sec]) according to the Cockcroft-Gault formula

• Negative screening test for human leukocyte antigen (HLA) -B x 5701 allele provided by Gilead Sciences

Key Exclusion Criteria:

• An opportunistic illness indicative of stage 3 HIV diagnosed within the 30 days prior to screening (refer to study protocol)

• Decompensated cirrhosis (e.g, 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

• Chronic Hepatitis B Virus (HBV) infection

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Related Conditions & MeSH terms

• HIV-1 Infection

Intervention

Drug:
• ABC/DTG/3TC
600/50/300 milligrams (mg) tablets administered orally, once daily
• B/F/TAF
50/200/25 mg tablets administered orally, once daily, without regard to food
• ABC/DTG/3TC Placebo
Tablets administered orally, once daily
• B/F/TAF Placebo
Tablets administered orally, once daily

Locations

Country	Name	City	State
Belgium	Cliniques Universitaires Saint-Luc	Brussels
Belgium	UZ Gent	Ghent
Canada	Clinique Medicale L'actuel	Montreal
Canada	Clinique OPUS Inc	Montreal
Canada	McGill University Health Center	Montreal
Canada	Ottawa Hospital	Ottawa
Canada	Maple Leaf Research	Toronto
Canada	Sunnybrook Health Sciences Centre	Toronto
Canada	Spectrum Health Care	Vancouver
Canada	Winnipeg Regional Health Authority	Winnipeg
Dominican Republic	Instituto Dominicano de Estudios Virologicos IDEV	Santo Domingo
France	Hôpital de La Croix Rousse	Lyon cedex 04
France	CHU de Nice Archet I	Nice
France	Hôpital Saint Antoine	Paris
France	Hôpital Saint Louis	PARIS cedex 10
France	Groupe Hospitalier Bichat Claude Bernard	Tourcoing
Germany	zibp Zentrum für Infektiologie Berlin Prenzlauer Berg GmbH	Berlin
Germany	Universitätsklinikum Bonn	Bonn
Germany	ICH Study Center	Hamburg
Italy	ASST Papa Giovanni XXIII - Azienda Ospedaliera Papa Giovanni XXIII	Bergamo
Italy	Ospedale San Raffaele S.r.l. - PPDS	Milano
Italy	Istituto Nazionale Malattie Infettive Lazzaro Spallanzani IRCCS	Roma
Puerto Rico	Hope Clinical Research	San Juan
Puerto Rico	University of Puerto Rico	San Juan
Spain	Hospital General Universitario de Alicante	Alicante
Spain	Hospital Universitario de Bellvitge	Badalona
Spain	Hospital Universitario Germans Trias i Pujol	Badalona	Barcelona
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	C.H. Regional Reina Sofia - PPDS	Cordoba
Spain	Hospital Clinico San Carlos	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario La Paz - PPDS	Madrid
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	CHUVI - H.U. Alvaro Cunqueiro	Vigo
United Kingdom	University Hospitals Birmingham NHS Foundation Trust	Birmingham
United Kingdom	Brighton and Sussex University Hospitals NHS Trust	Brighton
United Kingdom	Barts Health NHS Trust, Royal London Hospital, Ambrose King Centre	London
United Kingdom	Chelsea and Westminster NHS Trust	London
United Kingdom	Kings College Hospital	London
United Kingdom	Mortimer Market Centre	London
United Kingdom	Royal Free London NHS Foundation Trust	London
United Kingdom	North Manchester General Hospital - PPDS	Manchester
United States	Summa Health System	Akron	Ohio
United States	Upstate Infectious Disease Associates	Albany	New York
United States	Aids Research Consortium of Atlanta Inc	Atlanta	Georgia
United States	Atlanta Infectious Disease Group PC	Atlanta	Georgia
United States	Emory University	Atlanta	Georgia
United States	Augusta University	Augusta	Georgia
United States	Central Texas Clinical Research	Austin	Texas
United States	Saint Hope Foundation Inc	Bellaire	Texas
United States	Be Well Medical Center	Berkley	Michigan
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Bronx Care	Bronx	New York
United States	Montefiore Medical Center	Bronx	New York
United States	Evergreen Health	Buffalo	New York
United States	Aids Research Consortium of Atlanta Inc	Chapel Hill	North Carolina
United States	ID Consultants PA	Charlotte	North Carolina
United States	University of Cincinnati	Cincinnati	Ohio
United States	MetroHealth Research Institute	Cleveland	Ohio
United States	Medical University of South Carolina PPDS	Columbia	South Carolina
United States	Ohio State University Medical Center	Columbus	Ohio
United States	AIDS Arms Inc	Dallas	Texas
United States	North Texas Infectious Diseases Consultants PA	Dallas	Texas
United States	UT Southwestern Clinical Trials Office	Dallas	Texas
United States	Infectious Disease Specialists of Atlanta	Decatur	Georgia
United States	Apex Research	Denver	Colorado
United States	Henry Ford Health System	Detroit	Michigan
United States	Gary J. Richmond, M.D., P.A.	Fort Lauderdale	Florida
United States	Therafirst Medical Center	Fort Lauderdale	Florida
United States	Midway Immunology and Research Center	Fort Pierce	Florida
United States	East Carolina University	Greenville	North Carolina
United States	Gordon E Crofoot MD PA	Houston	Texas
United States	Research Access Network	Houston	Texas
United States	Therapeutic Concepts	Houston	Texas
United States	Rosedale Infectious Diseases	Huntersville	North Carolina
United States	Indiana CTSI Clinical Research Center	Indianapolis	Indiana
United States	Kansas City CARE Clinic	Kansas City	Missouri
United States	Diagnostic Clinic of Longview Center For Clinical Research (DCOL)	Longview	Texas
United States	Anthony Martin Mills MD A Medical Corporation, DBA Mills Clinical Research	Los Angeles	California
United States	Kaiser Permanente Medical Center	Los Angeles	California
United States	Ruane Clinical Research Group, Inc.	Los Angeles	California
United States	North Shore University Hospital-(Manhasset)	Manhasset	New York
United States	AHF Kinder Medical Group	Miami	Florida
United States	The Medical College of Wisconsin, Inc.	Milwaukee	Wisconsin
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Louisiana State University Health Sciences Center	New Orleans	Louisiana
United States	Prime healthcare services - St Michael's LLC d/b/a Saint Michael's medical center	Newark	New Jersey
United States	Alameda Health System- Highland Hospital	Oakland	California
United States	Orlando Immunology Center	Orlando	Florida
United States	AIDS Healthcare Foundation-Miami Beach	Pensacola	Florida
United States	Perelman Center for Advanced Medicine	Philadelphia	Pennsylvania
United States	Philadelphia FIGHT	Philadelphia	Pennsylvania
United States	Pueblo Family Physicians	Phoenix	Arizona
United States	Spectrum Medical Group	Phoenix	Arizona
United States	Allegheny Health Network	Pittsburgh	Pennsylvania
United States	Kaiser Permanente Medical Group	Sacramento	California
United States	University of California Davis	Sacramento	California
United States	Southampton Clinical Research Group, Inc.	Saint Louis	Missouri
United States	Southampton Healthcare Inc	Saint Louis	Missouri
United States	La Playa Medical Group	San Diego	California
United States	Kaiser Permanente	San Francisco	California
United States	Kaiser Permanente	San Leandro	California
United States	Chatham County Health Department	Savannah	Georgia
United States	Peter Shalit MD	Seattle	Washington
United States	South Jersey Infectious Disease	Somers Point	New Jersey
United States	Multicare Rockwood HIV Critical Care Clinic	Spokane	Washington
United States	Baystate Medical Center	Springfield	Massachusetts
United States	St. Joseph's Comprehensive Research Institute	Tampa	Florida
United States	The Lundquist Institute for BioMedical Innovation at Harbor-UCLA Medical Center	Torrance	California
United States	AIDS Research and Treatment Center of the Treasure Coast	Vero Beach	Florida
United States	Capital Medical Associates	Washington	District of Columbia
United States	Medical Faculty Associates	Washington	District of Columbia
United States	Providence Hospital - DC	Washington	District of Columbia
United States	Whitman-Walker Institute	Washington	District of Columbia
United States	Triple O Research Institute PA	West Palm Beach	Florida
United States	Wake Forest Baptist Medical Center - PPDS	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

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

References & Publications (20)

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

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

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;

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; Virtu

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-Naïve Clinical Trials. [Poster PEB150]. 11th IAS Conference on HIV Science (IAS 2021); 2021 July 18-21; Virtual.

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

Acosta R, Willkom M, Martin R, Chang S, Liu X, Hedskog C, et al. Low-frequency resistance variants in art-naïve participants do not affect bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) triple therapy outcome. [Poster MOPEB242]. 10th IAS Confer

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 par — View 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 Agen — View 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;

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-O

Gallant J, Lazzarin A, Mills A, Orkin C, Podzamczer D, Tebas P, Girard PM, Brar I, Daar ES, Wohl D, Rockstroh J, Wei X, Custodio J, White K, Martin H, Cheng A, Quirk E. Bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir, abacavir, a — View 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); 2

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- — View 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.

Ramgopal M, Maggiolo F, Ward D, Leboucche B, Rizzardini G, Molina JM, et al. Pooled Analysis of 4 International Trials of Bictegravir/Emtricitabine/Tenofovir Alafenamide (B/F/TAF) in Adults Aged = 65 Years Demonstrating Safety and Efficacy: Week 48 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.

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, a — View 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, — View 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.

* Note: There are 20 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Who Achieved HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm	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
Secondary	Percentage of Participants Who Achieved HIV-1 RNA < 50 Copies/mL at Week 96 as Defined by the US FDA-Defined Snapshot Algorithm	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.	Week 96
Secondary	Percentage of Participants Who Achieved HIV-1 RNA < 50 Copies/mL at Week 144 as Defined by the US FDA-Defined Snapshot Algorithm	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.	Week 144
Secondary	Percentage of Participants Who Achieved HIV-1 RNA < 20 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm	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.	Week 48
Secondary	Percentage of Participants Who Achieved HIV-1 RNA < 20 Copies/mL at Week 96 as Defined by the US FDA-Defined Snapshot Algorithm	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.	Week 96
Secondary	Percentage of Participants Who Achieved HIV-1 RNA < 20 Copies/mL at Week 144 as Defined by the US FDA-Defined Snapshot Algorithm	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.	Week 144
Secondary	Change From Baseline in log10 HIV-1 RNA at Week 48		Baseline, Week 48
Secondary	Change From Baseline in log10 HIV-1 RNA at Week 96		Baseline, Week 96
Secondary	Change From Baseline in log10 HIV-1 RNA at Week 144		Baseline, Week 144
Secondary	Change From Baseline in CD4+ Cell Count at Week 48		Baseline, Week 48
Secondary	Change From Baseline in CD4+ Cell Count at Week 96		Baseline, Week 96
Secondary	Change From Baseline in CD4+ Cell Count at Week 144		Baseline, Week 144
Secondary	Percentage Change From Baseline in Hip BMD at Week 48		Baseline, Week 48
Secondary	Percentage Change From Baseline in Hip BMD at Week 96		Baseline, Week 96
Secondary	Percentage Change From Baseline in Hip BMD at Week 144		Baseline, Week 144
Secondary	Percentage Change From Baseline in Spine BMD at Week 48		Baseline, Week 48
Secondary	Percentage Change From Baseline in Spine BMD at Week 96		Baseline, Week 96
Secondary	Percentage Change From Baseline in Spine BMD at Week 144		Baseline, Week 144
Secondary	Percentage of Participants Who Achieved HIV-1 RNA < 50 Copies/mL at Week 48 Open-Label as Defined by Missing = Excluded Algorithm	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. 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 non-missing HIV-1 RNA value at that visit.	Baseline, open-label Week 48
Secondary	Percentage of Participants Who Achieved HIV-1 RNA < 50 Copies/mL at Week 48 Open-Label as Defined by Missing = Failure Algorithm	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. 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.	Baseline, open-label Week 48
Secondary	Percentage of Participants Who Achieved HIV-1 RNA < 50 Copies/mL at Week 96 Open-Label as Defined by Missing = Excluded Algorithm	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. 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 non-missing HIV-1 RNA value at that visit.	Baseline, open-label Week 96
Secondary	Percentage of Participants Who Achieved HIV-1 RNA < 50 Copies/mL at Week 96 Open-Label as Defined by Missing = Failure Algorithm	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. 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.	Baseline, open-label Week 96
Secondary	Change From Baseline in CD4+ Cell Count at Week 48 Open-Label		Baseline, open-label Week 48
Secondary	Change From Baseline in CD4+ Cell Count at Week 96 Open-Label		Baseline, open-label Week 96