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

Phase 3Active Not RecruitingNCT06544733

Gilead Sciences675 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

675

Conditions

HIV-1-Infection

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Phase 2: Proportion of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 24 as Determined by the United States (US) Food and Drug Administration (FDA)-defined Snapshot Algorithm

Time frame: Week 24

Phase 3: Proportion of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm

Time frame: Week 48

Secondary Outcomes

Phase 2: Proportion of Participants With HIV-1 RNA ≥ 50 copies/mL at Week 12 as Determined by the US FDA-defined Snapshot Algorithm

Time frame: Week 12

Phase 2: Proportion of Participants With HIV-1 RNA ≥ 50 copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm

Time frame: Week 48

Phase 2: Proportion of Participants With HIV-1 RNA < 50 Copies/mL at Week 12 as Determined by the US FDA-defined Snapshot Algorithm

Time frame: Week 12

Phase 2: Proportion of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 as Determined by the US FDA-defined Snapshot Algorithm

Time frame: Week 24

Phase 2: Proportion of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm

Time frame: Week 48

Phase 2: Change From Baseline in Clusters of Differentiation 4 (CD4+) T-cell Count at Week 12

Time frame: Baseline, Week 12

Phase 2: Change From Baseline in CD4+ T-cell Count at Week 24

Time frame: Baseline, Week 24

Phase 2: Change From Baseline in CD4+ T-cell Count at Week 48

Time frame: Baseline, Week 48

Phase 2: Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs) Through Week 12

Time frame: First dose date up to Week 12

Phase 2: Percentage of Participants Experiencing TEAEs Through Week 24

Time frame: First dose date up to Week 24

Phase 2: Percentage of Participants Experiencing TEAEs Through Week 48

Time frame: First dose date up to Week 48

Phase 2: Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities Through Week 12

Time frame: First dose date up to Week 12

Phase 2: Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities Through Week 24

Time frame: First dose date up to Week 24

Phase 2: Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities Through Week 48

Time frame: First dose date up to Week 48

Phase 2: Pharmacokinetic (PK) Parameter: Cmax of Lepetegravir and Lenacapavir (LEN)

Cmax is defined as the maximum observed concentration of drug.

Time frame: Day 1 up to Week 48

Phase 2: PK Parameter: Tmax of Lepetegravir and LEN

Tmax is defined as the time (observed time point) of Cmax.

Time frame: Day 1 up to Week 48

Phase 2: PK Parameter: Ctau of Lepetegravir and LEN

Ctau is defined as the observed drug concentration at the end of the dosing interval.

Time frame: Day 1 up to Week 48

Phase 2: PK Parameter: AUCtau of Lepetegravir and LEN

AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

Time frame: Day 1 up to Week 48

Phase 3: Proportion of Participants With HIV-1 RNA ≥ 50 copies/mL at Week 96 as Determined by the US FDA-defined Snapshot Algorithm

Time frame: Week 96

Phase 3: Proportion of Participants With HIV-1 RNA < 50 copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm

Time frame: Week 48

Phase 3: Proportion of Participants With HIV-1 RNA < 50 copies/mL at Week 96 as Determined by the US FDA-defined Snapshot Algorithm

Time frame: Week 96

Phase 3: Change From Baseline in CD4+ T-cell Count at Week 48

Time frame: Baseline, Week 48

Phase 3: Change From Baseline in CD4+ T-cell Count at Week 96

Time frame: Baseline, Week 96

Phase 3: Percentage of Participants Experiencing TEAEs Through Week 48

Time frame: First dose date up to Week 48

Phase 3: Proportion of Participants Experiencing TEAEs Through Week 96

Time frame: First dose date up to Week 96

Phase 3: Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities Through Week 48

Time frame: First dose date up to Week 48

Phase 3: Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities Through Week 96

Time frame: First dose date up to Week 96

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

Overview

Conditions

Interventions

Eligibility

Locations (39)

Outcomes

Primary Outcomes

Secondary Outcomes