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

An Operationally Seamless Phase 2/3, Randomized, Active-Controlled Study Evaluating the Safety and Efficacy of an Oral Weekly Regimen of GS-1720 in Combination With GS-4182 Versus Biktarvy in Virologically Suppressed People With HIV-1

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.

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.