Study of Oral Weekly GS-1720 and GS-4182 Compared With Biktarvy in People With HIV-1 Who Have Not Been Treated

Purpose

The goal of this clinical study is to learn more about the experimental drugs GS-1720 (an oral, long-acting integrase strand transfer inhibitor (INSTI)) and GS-4182 (a prodrug of Lenacapavir (LEN)); to compare the combination of GS-1720 and GS-4182 with the current standard-of-care treatment bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (Biktarvy), 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 in treatment-naive people with HIV-1 (PWH). This study has two phases: Phase 2 and Phase 3. The primary objectives of this study are: Phase 2: To evaluate the efficacy of oral weekly GS-1720 coadministered with GS-4182 versus continuing Biktarvy (BVY) in treatment-naive PWH at Week 24. Phase 3: To evaluate the efficacy of oral weekly GS-1720/GS-4182 fixed-dose combination (FDC) tablet regimen versus continuing BVY in treatment-naive PWH at Week 48.

Condition

  • HIV-1-infection

Eligibility

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

Inclusion Criteria

  • HIV-1 RNA ≥ 500 copies/mL at screening. - Antiretroviral (ARV) treatment-naive, except the use of oral pre-exposure prophylaxis (PrEP) or postexposure prophylaxis (PEP) with emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) or F/TAF, up to 1 month prior to screening.

Exclusion Criteria

  • Prior use of any long acting parenteral antiretrovirals (ARVs) such as monoclonal antibodies, broadly neutralizing antibodies targeting HIV-1, LEN, injectable cabotegravir (including oral cabotegravir lead-in), and/or injectable rilpivirine. - Documented resistance to the integrase strand-transfer inhibitor class, specifically, resistance-associated mutations E92G/Q, G118R, F121Y, Y143C/H/R, S147G, Q148H/K/R, N155H/S, or R263K in the integrase gene. - Any of the following laboratory values at screening: 1. CD4 cell count < 200 cells/mm3 at screening. 2. Estimated glomerular filtrations arate < 60 mL/min according to the Modification of Diet in Renal Disease formula. 3. Hepatic transaminases (aspartate aminotransferase and alanine aminotransferase) > 1.5 × upper limit of normal (ULN). 4. Direct bilirubin > 1.5 × ULN. 5. Platelets count < 50,000 cells/mm3. 6. Hemoglobin < 8.0 g/dL. - Active or occult hepatitis B virus infection. - Active hepatitis C virus infection. 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 of the study has 2 periods: Randomized and Extension, which are both open label. Phase 3 of the study has 2 periods: Randomized Period which would be double-blind (at least Week 96), followed by an Extension Period which will be Open-label.

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Phase 2: GS-1720 + GS-4182 (Treatment Group 1) 		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: B/F/TAF (Treatment Group 2) 		Participants will receive B/F/TAF (50/200/25 mg) 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 (650/300 mg) weekly. Phase 2 Treatment Group 2 will receive a loading dose of GS-1720/GS-4182 FDC (1300 mg/600 mg) on Extension Phase Day 1, then GS-1720/GS-4182 FDC (650/300 mg) 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) B/F/TAF (Treatment Group 1) 		Participants will receive a 1-day loading dose of GS-1720/GS-4182 FDC on Day 1. Thereafter, participants will receive GS-1720/GS-4182 FDC tablets weekly + PTM B/F/TAF once daily. Participants will receive treatment for at least 96 weeks.
  • Drug: GS-1720/GS-4182 FDC
    Tablets administered orally without regard to food
  • Drug: Placebo to Match BVY
    Tablets administered orally without regard to food
Active Comparator
Phase 3: B/F/TAF + PTM GS-1720/GS-4182 FDC (Treatment Group 2) 		Participants will receive oral B/F/TAF daily along with PTM GS-1720/GS-4182 FDC weekly for at least 96 weeks. Additionally, participants will receive a 1-day loading dose of PTM GS-1720/GS-4182 on Day 1.
  • 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 continue to receive GS-1720/GS-4182 FDC weekly while PTM B/F/TAF will be discontinued. Phase 3 Treatment Group 2 will switch to receive GS-1720/GS-4182 FDC tablets weekly. Participants in Treatment Group 2 will also receive a 1-day loading dose of GS-1720/GS-4182 FDC on Extension Phase Day 1. Participants who choose to enter the Phase 3 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

More Details

Status
Active, not recruiting
Sponsor
Gilead Sciences

Study Contact