Safety and Efficacy of Switching From Dolutegravir and ABC/3TC or ABC/DTG/3TC to B/F/TAF in HIV-1 Infected Adults Who Are Virologically Suppressed

A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of Switching From a Regimen of Dolutegravir and ABC/3TC, or a Fixed Dose Combination (FDC) of ABC/DTG/3TC to a FDC of GS-9883/F/TAF in HIV-1 Infected Subjects Who Are Virologically Suppressed

The primary objective of this study is to evaluate the efficacy of switching from a regimen of dolutegravir (DTG) and abacavir/lamivudine (ABC/3TC) or a fixed dose combination (FDC) of abacavir/dolutegravir/lamivudine (ABC/DTG/3TC) to a FDC of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) versus continuing DTG and ABC/3TC as the FDC ABC/DTG/3TC in virologically suppressed Human Immunodeficiency Virus- 1 (HIV-1) infected adults.

Study Overview

• Status: Completed
• Conditions: HIV-1 Infection
• Intervention / Treatment: Drug: B/F/TAF; Drug: ABC/DTG/3TC Placebo; Drug: ABC/DTG/3TC; Drug: B/F/TAF Placebo

• Study Type: Interventional
• Enrollment (Actual): 567
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2010 NSW
    • Sydney, New South Wales, Australia, 2010
• Belgium
  • Ghent, Belgium, 9000
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 2T1
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3A 1R9
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
    • Montreal, Quebec, Canada, H2l 4P9
    • Montreal, Quebec, Canada, H3A 1T1
• France
  • NICE Cedex 03, France, 6202
  • Nantes, France, 44093
  • Paris, France, 75010
  • Paris cedex 20, France, 75970
• Germany
  • Berlin, Germany, 13353
  • Berlin, Germany, 12157
  • Bonn, Germany, 53127
  • Essen, Germany, 45122
  • Frankfurt am Main, Germany, 60596
  • Hamburg, Germany, 20146
  • Munich, Germany, 80336
  • München, Germany, 80335
• Italy
  • Roma, Italy, 00149
• Puerto Rico
  • San Juan, Puerto Rico, 00909
  • San Juan, Puerto Rico, 00909-1711
• Spain
  • Badalona, Spain, 08916
  • Badalona, Spain, 8907
  • Barcelona, Spain, 8025
  • Cordoba, Spain, 14004
  • Madrid, Spain, 28034
  • Santiago de Compostela, Spain, 15706
  • Sevilla, Spain, 41013
• United Kingdom
  • Brighton, United Kingdom, BN2 3EW
  • Manchester, United Kingdom, M8 5RB
  • Manchester, United Kingdom, M13 0FH
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85012
  • California
    • Beverly Hills, California, United States, 90211
    • Los Angeles, California, United States, 90027
    • Los Angeles, California, United States, 90036
    • Los Angeles, California, United States, 90033
    • Los Angeles, California, United States, 90069
    • Oakland, California, United States, 94609
    • Oakland, California, United States, 94602
    • Palm Springs, California, United States, 92264
    • Sacramento, California, United States, 95825
    • Sacramento, California, United States, 95187
    • San Leandro, California, United States, 94577
  • District of Columbia
    • Washington, District of Columbia, United States, 20009
    • Washington, District of Columbia, United States, 20036
  • Florida
    • DeLand, Florida, United States, 32720
    • Fort Lauderdale, Florida, United States, 33308
    • Fort Lauderdale, Florida, United States, 33316
    • Fort Pierce, Florida, United States, 34982
    • Miami, Florida, United States, 33133
    • Miami Beach, Florida, United States, 33139
    • Orlando, Florida, United States, 32803
    • Pensacola, Florida, United States, 32504
    • Tampa, Florida, United States, 33614
    • Vero Beach, Florida, United States, 32960
    • West Palm Beach, Florida, United States, 33401
    • Wilton Manors, Florida, United States, 33305
  • Georgia
    • Augusta, Georgia, United States, 30912
    • Decatur, Georgia, United States, 30033
    • Macon, Georgia, United States, 31201
    • Savannah, Georgia, United States, 31401
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
  • Illinois
    • Chicago, Illinois, United States, 60613
    • Chicago, Illinois, United States, 60657
  • Kentucky
    • Louisville, Kentucky, United States, 40202
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
  • Massachusetts
    • Boston, Massachusetts, United States, 02118-2393
    • Springfield, Massachusetts, United States, 01105
  • Michigan
    • Berkley, Michigan, United States, 48072
    • Detroit, Michigan, United States, 48202
  • Minnesota
    • Minneapolis, Minnesota, United States, 55415
  • Missouri
    • Kansas City, Missouri, United States, 64111
    • Saint Louis, Missouri, United States, 63139
  • New Jersey
    • Newark, New Jersey, United States, 07102
  • New Mexico
    • Santa Fe, New Mexico, United States, 87505
  • New York
    • Bronx, New York, United States, 10467-2490
    • Buffalo, New York, United States, 14215
    • New York, New York, United States, 10011
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
    • Greenville, North Carolina, United States, 27834
    • Huntersville, North Carolina, United States, 28078
  • Ohio
    • Cincinnati, Ohio, United States, 45267-0560
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
  • South Carolina
    • Columbia, South Carolina, United States, 29203-6840
  • Texas
    • Austin, Texas, United States, 78705
    • Dallas, Texas, United States, 75246
    • Dallas, Texas, United States, 75219
    • Houston, Texas, United States, 77004
    • Houston, Texas, United States, 77098
    • Longview, Texas, United States, 75605
  • Washington
    • Seattle, Washington, United States, 98104
    • Spokane, Washington, United States, 99204

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Estimated glomerular filtration rate ≥ 50 mL/min (≥ 0.83 mL/sec).
• Currently receiving an antiretroviral regimen of DTG + ABC/3TC, or ABC/DTG/3TC FDC for ≥ 3 months prior to the screening visit.
• HIV ribonucleic acid (RNA) < 50 copies/mL at the screening visit.
• Currently on a stable regimen for ≥ 3 months preceding the screening visit with documented plasma HIV-1 RNA < 50 copies/mL for ≥ 3 months preceding the screening visit (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL).
• Have no documented or suspected resistance to emtricitabine (FTC), tenofovir (TFV), DTG, ABC or 3TC.

Key Exclusion Criteria:

• Current alcohol or substance use judged by the Investigator to potentially interfere with subject study compliance.
• Active tuberculosis infection.
• Individuals experiencing decompensated cirrhosis (eg, ascites, encephalopathy, or variceal bleeding).
• Females who are pregnant.
• Females who are breastfeeding.
• Acute hepatitis in the 30 days prior to study entry.
• Chronic Hepatitis B Virus (HBV) infection.

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Blinded Phase: B/F/TAF; B/F/TAF + ABC/DTG/3TC placebo for at least 48 weeks	Drug: B/F/TAF; 50/200/25 mg FDC tablets administered orally once daily without regard to food; Other Names: Bictegravir (previously referred to as GS-9883)/Emtricitabine/Tenofovir Alafenamide; Biktarvy® [BVY]; Drug: ABC/DTG/3TC Placebo; Tablets administered orally once daily without regard to food
Active Comparator: Blinded Phase: ABC/DTG/3TC; ABC/DTG/3TC + B/F/TAF placebo for at least 48 weeks	Drug: ABC/DTG/3TC; 600/50/300 mg FDC tablets administered orally once daily without regard to food; Other Names: Triumeq®; Drug: B/F/TAF Placebo; Tablets administered orally once daily without regard to food
Experimental: Open-Label Phase; At the End of Blinded Treatment Visit, if safety and efficacy of B/F/TAF is demonstrated following review of unblinded data, participants in a country where B/F/TAF FDC is not available will be given the option to receive B/F/TAF FDC in an open-label extension phase for up to 96 weeks, or until the product becomes accessible to subjects through an access program, or until Gilead Sciences elects to discontinue the study in that country, whichever occurs first.	Drug: B/F/TAF; 50/200/25 mg FDC tablets administered orally once daily without regard to food; Other Names: Bictegravir (previously referred to as GS-9883)/Emtricitabine/Tenofovir Alafenamide; Biktarvy® [BVY]

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Virologic Failure (HIV-1 RNA ≥ 50 Copies/mL) as Defined by the Modified 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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in CD4+ Cell Count at Week 48		Baseline; Week 48
Percentage of Participants With HIV-1 RNA < 50 Copies/mL 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
Spine Bone Mineral Density (BMD) at Baseline		Baseline
Percentage Change From Baseline in Spine BMD at Week 48		Baseline; Week 48
Hip Bone Mineral Density at Baseline		Baseline
Percentage Change From Baseline in Hip BMD at Week 48		Baseline; Week 48

Collaborators and Investigators

• Sponsor: Gilead Sciences

Publications and helpful links

General Publications

• Andreatta K, Willkom M, Martin R, Chang S, Wei L, Liu H, Liu YP, Graham H, Quirk E, Martin H, White KL. Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I. J Antimicrob Chemother. 2019 Dec 1;74(12):3555-3564. doi: 10.1093/jac/dkz347. Erratum In: J Antimicrob Chemother. 2019 Dec 1;74(12):3646-3647.
• Molina JM, Ward D, Brar I, Mills A, Stellbrink HJ, Lopez-Cortes L, Ruane P, Podzamczer D, Brinson C, Custodio J, Liu H, Andreatta K, Martin H, Cheng A, Quirk E. Switching to fixed-dose bictegravir, emtricitabine, and tenofovir alafenamide from dolutegravir plus abacavir and lamivudine in virologically suppressed adults with HIV-1: 48 week results of a randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial. Lancet HIV. 2018 Jul;5(7):e357-e365. doi: 10.1016/S2352-3018(18)30092-4. Epub 2018 Jun 18. Erratum In: Lancet HIV. 2018 Jun 22;:
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2015
• Primary Completion (Actual): May 9, 2017
• Study Completion (Actual): October 23, 2019

Study Registration Dates

• First Submitted: November 10, 2015
• First Submitted That Met QC Criteria: November 10, 2015
• First Posted (Estimate): November 11, 2015

Study Record Updates

• Last Update Posted (Actual): November 12, 2020
• Last Update Submitted That Met QC Criteria: October 22, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Tenofovir; Emtricitabine; Emtricitabine tenofovir alafenamide; Lamivudine; Triumeq
• Other Study ID Numbers: GS-US-380-1844; 2015-004025-14 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at https://www.gilead.com/science-and-medicine/research/clinical-trials-transparency-and-data-sharing-policy.
• IPD Sharing Time Frame: 18 months after study completion
• IPD Sharing Access Criteria: A secured external environment with username, password, and RSA code.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No