Study of Oral Weekly GS-1720 and GS-4182 Versus Biktarvy in People With HIV-1 Who Are Virologically Suppressed

Purpose

The goal of this clinical study is to learn more about the experimental drugs GS-1720 and GS-4182; to compare the combination of GS-1720 and GS-4182 with the current standard-of-care treatment bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF, BVY), to see if the combination of GS-1720 and GS-4182 is safe and if it works for treating human immunodeficiency virus type 1 (HIV-1) infection. This study has two phases: Phase 2 and Phase 3. The primary objectives of this study are: Phase 2: To evaluate the efficacy of switching to oral weekly GS-1720 in combination with GS-4182 versus continuing BVY in virologically suppressed people with HIV-1 (PWH) at Week 24. Phase 3: To evaluate the efficacy of switching to oral weekly GS-1720/GS-4182 Fixed-dose combination (FDC) tablet regimen versus continuing BVY in virologically suppressed PWH at Week 48.

Condition

  • HIV-1-Infection

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Documented plasma HIV-1 RNA < 50 copies/mL for ≥ 24 weeks before and at screening. - Receiving BVY for ≥ 24 weeks prior to screening.

Exclusion Criteria

  • Prior use of, or exposure to LEN, GS-1720, or GS-4182. - History of virologic failure while on an integrase strand-transfer inhibitor (INSTI)-based regimen. - Documented integrase strand-transfer inhibitor (INSTI) resistance, specifically, resistance-associated mutations (RAMs) E92G/Q, G118R, F121Y, Y143C/H/R, S147G, Q148H/K/R, N155H/S, or R263K in the integrase gene. - Prior use of any long-acting (LA) parenteral antiretrovirals (ARV) such as monoclonal antibodies (mAbs) or broadly neutralizing antibodies (bNAbs) targeting HIV-1, injectable cabotegravir (including oral cabotegravir lead-in), or injectable rilpivirine. - Any of the following laboratory values at screening: - Clusters of differentiation 4 (CD4) cell count < 200 cells/mm^3 at screening - Glomerular filtration rate < 60 mL/min according to the Modification of Diet in Renal Disease formula - Hepatic transaminases (aspartate aminotransferase (AST) and alanine aminotransferase (ALT) > 1.5 × upper limit of normal (ULN) - Direct bilirubin > 1.5 × ULN - Platelets count < 50,000 cells/mm^3 - Hemoglobin < 8.0 g/dL - Active or occult hepatitis B virus (HBV) infection. - Active hepatitis C virus (HCV). Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Design

Phase
Phase 2/Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
Double (Participant, Investigator)
Masking Description
Phase 2 (Treatment Group 1, Treatment Group 2, and Extension Phase) arms and Phase 3 Extension Phase arm are open-label; Phase 3 Treatment Group 1 and Phase 3 Treatment Group 2 arms are blinded.

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Phase 2: GS-1720 + GS-4182 (Treatment Group 1) 		Participants who have been virologically suppressed on bictegravir/emtricitabine/tenofovir alafenamide (BVY) will switch to GS-1720 (650 mg tablet) and GS-4182 (300 mg tablet) coadministered. Participants will receive a 1-day loading dose of GS-1720 (1300 mg) and GS-4182 (600 mg) on Day 1. Thereafter, participants will take weekly doses of single agent GS-1720 (650 mg) and GS-4182 (300 mg) coadministered for at least 48 weeks.
  • Drug: GS-1720
    Tablets administered orally without regard to food
  • Drug: GS-4182
    Tablets administered orally without regard to food
Active Comparator
Phase 2: Bictegravir/emtricitabine/tenofovir alafenamide (BVY) (Treatment Group 2) 		Participants who have been virologically suppressed on bictegravir/emtricitabine/tenofovir alafenamide (BVY) will continue receiving BVY daily for at least 48 weeks.
  • Drug: Bictegravir/emtricitabine/tenofovir alafenamide
    Tablets administered orally without regard to food
    Other names:
    • Biktarvy®
Experimental
Phase 2 Extension Phase: GS-1720/GS-4182 Fixed-dose Combination (FDC) 		At the end of the randomized treatment, Phase 2 participants will be given the option to participate in the Extension Phase. Phase 2 Treatment Group 1 will switch to GS-1720/GS-4182 FDC weekly. Phase 2 Treatment Group 2 will receive a loading dose of GS-1720/GS-4182 FDC on Extension Phase Day 1 then, GS-1720/GS-4182 FDC weekly. Participants who choose to enter the Extension Phase will receive GS-1720/GS-4182 FDC tablets until the product becomes available or until Gilead Sciences elects to discontinue the study, whichever occurs first.
  • Drug: GS-1720/GS-4182 FDC
    Tablets administered orally without regard to food
Experimental
Phase 3: GS-1720/GS-4182 FDC + Placebo to Match (PTM) BVY (Treatment Group 1) 		Participants who have been virologically suppressed on BVY will switch from BVY to GS-1720/GS-4182 FDC tablets weekly + placebo-to-match (PTM) BVY once daily. In addition, participants will receive a 1-day loading dose regimen of GS-1720/GS-4182 FDC on Day 1. Participants will receive treatment for at least 96 weeks.
  • Drug: Placebo to Match BVY
    Tablets administered orally without regard to food
  • Drug: GS-1720/GS-4182 FDC
    Tablets administered orally without regard to food
Active Comparator
Phase 3: BVY Placebo to Match GS-1720/GS-4182 FDC + BVY (Treatment Group 2) 		Participants who have been virologically suppressed on BVY will continue receiving oral BVY daily. In addition, participants will receive a 1-day loading dose of PTM GS-1720/GS-4182 on Day 1 and weekly PTM thereafter. Participants will receive treatment for at least 96 weeks.
  • Drug: Bictegravir/emtricitabine/tenofovir alafenamide
    Tablets administered orally without regard to food
    Other names:
    • Biktarvy®
  • Drug: Placebo to Match GS1720/GS-4182 FDC
    Tablets administered orally without regard to food
Experimental
Phase 3 Extension Phase: GS-1720/GS-4182 Fixed-dose Combination (FDC) 		After the end of blinded treatment, Phase 3 participants will be given the option to participate in the Extension Phase. Phase 3 Treatment Group 1 will switch to GS-1720/GS-4182 FDC weekly. Phase 3 Treatment Group 2 will receive a 1-day loading dose of GS-1720/GS-4182 FDC on Extension Phase Day 1, then GS-1720/GS-4182 FDC weekly. Participants who choose to enter the Extension Phase will receive GS-1720/GS-4182 FDC tablets until the product becomes available or until Gilead Sciences elects to discontinue the study, whichever occurs first.
  • Drug: GS-1720/GS-4182 FDC
    Tablets administered orally without regard to food

Recruiting Locations

Georgetown University Medical Center
Washington, District of Columbia 20007

More Details

Status
Recruiting
Sponsor
Gilead Sciences

Study Contact

Gilead Clinical Study Information Center
1-833-445-3230 (GILEAD-0)
GileadClinicalTrials@gilead.com