Study of Oral Weekly Lepetegravir (Formerly GS-1720) and Lenacapavir Pacfosacil (Formerly GS-4182) Versus Biktarvy in People With HIV-1 Who Are Virologically Suppressed (WONDERS1)

Gilead Sciences

Status and phase: Active, not recruiting; Phase 3; Phase 2

Conditions: HIV-1-Infection

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

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 lepetegravir and lenacapavir pacfosacil; to compare the combination of lepetegravir and lenacapavir pacfosacil with the current standard-of-care treatment bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF, BVY), to see if the combination of lepetegravir and lenacapavir pacfosacil 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 lepetegravir in combination with lenacapavir pacfosacil 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 lepetegravir /lenacapavir pacfosacil 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, lepetegravir, or lenacapavir pacfosacil.

• 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: Lepetegravir + Lenacapavir pacfosacil (Treatment Group 1)

Experimental group

Description:

Participants who have been virologically suppressed on bictegravir/emtricitabine/tenofovir alafenamide (BVY) will switch to lepetegravir (650 mg tablet) and lenacapavir pacfosacil (300 mg tablet) coadministered. Participants will receive a 1-day loading dose of lepetegravir (1300 mg) and lenacapavir pacfosacil (600 mg) on Day 1. Thereafter, participants will take weekly doses of single agent lepetegravir (650 mg) and lenacapavir pacfosacil (300 mg) coadministered for at least 48 weeks.

Treatment:

Drug: Lenacapavir pacfosacil

Drug: Lepetegravir

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: Lepetegravir /Lenacapavir pacfosacil 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 lepetegravir /lenacapavir pacfosacil FDC weekly. Phase 2 Treatment Group 2 will receive a loading dose of lepetegravir /lenacapavir pacfosacil FDC on Extension Phase Day 1 then, lepetegravir/lenacapavir pacfosacil FDC weekly. Participants who choose to enter the Extension Phase will receive lepetegravir /lenacapavir pacfosacil FDC tablets until the product becomes available or until Gilead Sciences elects to discontinue the study, whichever occurs first.

Treatment:

Drug: Lepetegravir/Lenacapavir pacfosacil FDC

Phase 3: Lepetegravir /Lenacapavir pacfosacil 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 lepetegravir/lenacapavir pacfosacil FDC tablets weekly + placebo-to-match (PTM) BVY once daily. In addition, participants will receive a 1-day loading dose regimen of lepetegravir /lenacapavir pacfosacil FDC on Day 1. Participants will receive treatment for at least 96 weeks.

Treatment:

Drug: Placebo to Match BVY

Drug: Lepetegravir/Lenacapavir pacfosacil FDC

Phase 3: BVY Placebo to Match Lepetegravir /Lenacapavir pacfosacil 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 lepetegravir /lenacapavir pacfosacil 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: Lepetegravir/Lenacapavir pacfosacil 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 lepetegravir/lenacapavir pacfosacil FDC weekly. Phase 3 Treatment Group 2 will receive a 1-day loading dose of lepetegravir/lenacapavir pacfosacil FDC on Extension Phase Day 1, then lepetegravir/lenacapavir pacfosacil FDC weekly. Participants who choose to enter the Extension Phase will receive lepetegravir/lenacapavir pacfosacil FDC tablets until the product becomes available or until Gilead Sciences elects to discontinue the study, whichever occurs first.

Treatment:

Drug: Lepetegravir/Lenacapavir pacfosacil FDC