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

Gilead Sciences

Status and phase: Enrolling; Phase 3; Phase 2

Conditions: HIV-1-infection

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT06613685

2024-512505-66 (Other Identifier)

GS-US-695-7156

Details and patient eligibility

About

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.

Enrollment: 675 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key 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.

Key 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.

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 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: B/F/TAF (Treatment Group 2)

Active Comparator group

Description:

Participants will receive B/F/TAF (50/200/25 mg) 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 (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.

Treatment:

Drug: GS-1720/GS-4182 FDC

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

Experimental group

Description:

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.

Treatment:

Drug: GS-1720/GS-4182 FDC

Drug: Placebo to Match BVY

Phase 3: B/F/TAF + PTM GS-1720/GS-4182 FDC (Treatment Group 2)

Active Comparator group

Description:

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.

Treatment:

Drug: Placebo to Match GS1720/GS-4182 FDC

Drug: Bictegravir/emtricitabine/tenofovir alafenamide

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 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.

Treatment:

Drug: GS-1720/GS-4182 FDC