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

• ClinicalTrials.gov Identifier: NCT02603120
• Recruitment Status: Completed
• First Posted: November 11, 2015
• Results First Posted: July 23, 2018
• Last Update Posted: November 12, 2020
• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

Tracking Information

• First Submitted Date: November 10, 2015
• First Posted Date: November 11, 2015
• Results First Submitted Date: May 1, 2018
• Results First Posted Date: July 23, 2018
• Last Update Posted Date: November 12, 2020
• Actual Study Start Date: November 11, 2015
• Actual Primary Completion Date: May 9, 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 25, 2018)

Percentage of Participants With Virologic Failure (HIV-1 RNA ≥ 50 Copies/mL) as Defined by the Modified US FDA-defined Snapshot Algorithm [ Time Frame: Week 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.

• Original Primary Outcome Measures (submitted: November 10, 2015): Proportion of participants with virologic failure (HIV-1 RNA ≥ 50 copies/mL) as defined by the modified US FDA snapshot algorithm [ Time Frame: Week 48 ]

Current Secondary Outcome Measures (submitted: June 25, 2018)

• Percentage of Participants With HIV-1 RNA < 50 Copies/mL as Defined by the US FDA-defined Snapshot Algorithm [ Time Frame: Week 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.
• Change From Baseline in CD4+ Cell Count at Week 48 [ Time Frame: Baseline; Week 48 ]
• Spine Bone Mineral Density (BMD) at Baseline [ Time Frame: Baseline ]
• Percentage Change From Baseline in Spine BMD at Week 48 [ Time Frame: Baseline; Week 48 ]
• Hip Bone Mineral Density at Baseline [ Time Frame: Baseline ]
• Percentage Change From Baseline in Hip BMD at Week 48 [ Time Frame: Baseline; Week 48 ]

Original Secondary Outcome Measures (submitted: November 10, 2015)

• Proportion of participants with HIV-1 RNA < 50 copies/mL as defined by the US FDA snapshot algorithm [ Time Frame: Week 48 ]
• Change from baseline in CD4+ cell count at Week 48 [ Time Frame: Baseline and Week 48 ]
• Percentage change from baseline in hip and spine bone mineral density (BMD) at Week 48 [ Time Frame: Baseline and Week 48 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• Official Title: 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
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: HIV-1 Infection

Intervention

• Drug: ABC/DTG/3TC
  600/50/300 mg FDC tablets administered orally once daily without regard to food
  Other Name: Triumeq®
• 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
• Drug: B/F/TAF Placebo
  Tablets administered orally once daily without regard to food

Study Arms

• Experimental: Blinded Phase: B/F/TAF
  B/F/TAF + ABC/DTG/3TC placebo for at least 48 weeks
  Interventions:

  • Drug: B/F/TAF
  • Drug: ABC/DTG/3TC Placebo
• Active Comparator: Blinded Phase: ABC/DTG/3TC
  ABC/DTG/3TC + B/F/TAF placebo for at least 48 weeks
  Interventions:

  • Drug: ABC/DTG/3TC
  • Drug: B/F/TAF Placebo
• 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.
  Intervention: Drug: B/F/TAF

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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 19, 2017): 567
• Original Estimated Enrollment (submitted: November 10, 2015): 520
• Actual Study Completion Date: October 23, 2019
• Actual Primary Completion Date: May 9, 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Belgium, Canada, France, Germany, Italy, Puerto Rico, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT02603120
• Other Study ID Numbers: GS-US-380-1844; 2015-004025-14 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• 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.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Time Frame: 18 months after study completion
• Access Criteria: A secured external environment with username, password, and RSA code.
• URL: https://www.gilead.com/science-and-medicine/research/clinical-trials-transparency-and-data-sharing-policy

• Current Responsible Party: Gilead Sciences
• Original Responsible Party: Same as current
• Current Study Sponsor: Gilead Sciences
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Gilead Study Director; Gilead Sciences

• PRS Account: Gilead Sciences
• Verification Date: October 2020