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

Gilead Sciences

Status and phase: Enrolling; Phase 3; Phase 2

Conditions: HIV-1-Infection

Treatments: Drug: Placebo to Match BVY; Drug: Placebo to Match GS1720/GS-4182 FDC; Drug: GS-4182; Drug: GS-1720/GS-4182 FDC; Drug: Bictegravir/emtricitabine/tenofovir alafenamide; Drug: GS-1720

Study type: Interventional

Funder types: Industry

Identifiers

NCT06544733

2024-511054-50 (Other Identifier)

GS-US-695-6509

Details and patient eligibility

About

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.

Enrollment: 675 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key 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.

Key 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Double Blind

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675 participants in 6 patient groups

Phase 2: GS-1720 + GS-4182 (Treatment Group 1)

Experimental group

Description:

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.

Treatment:

Drug: GS-1720

Drug: GS-4182

Phase 2: Bictegravir/emtricitabine/tenofovir alafenamide (BVY) (Treatment Group 2)

Active Comparator group

Description:

Participants who have been virologically suppressed on bictegravir/emtricitabine/tenofovir alafenamide (BVY) will continue receiving BVY daily for at least 48 weeks.

Treatment:

Drug: Bictegravir/emtricitabine/tenofovir alafenamide

Phase 2 Extension Phase: GS-1720/GS-4182 Fixed-dose Combination (FDC)

Experimental group

Description:

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.

Treatment:

Drug: GS-1720/GS-4182 FDC

Phase 3: GS-1720/GS-4182 FDC + Placebo to Match (PTM) BVY (Treatment Group 1)

Experimental group

Description:

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.

Treatment:

Drug: GS-1720/GS-4182 FDC

Drug: Placebo to Match BVY

Phase 3: BVY Placebo to Match GS-1720/GS-4182 FDC + BVY (Treatment Group 2)

Active Comparator group

Description:

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.

Treatment:

Drug: Bictegravir/emtricitabine/tenofovir alafenamide

Drug: Placebo to Match GS1720/GS-4182 FDC

Phase 3 Extension Phase: GS-1720/GS-4182 Fixed-dose Combination (FDC)

Experimental group

Description:

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.

Treatment:

Drug: GS-1720/GS-4182 FDC