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
Overview
- Phase
- Phase 2
- Intervention
- Lepetegravir
- Conditions
- HIV-1-Infection
- Sponsor
- Gilead Sciences
- Enrollment
- 675
- Locations
- 70
- Primary Endpoint
- 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
- Status
- Active, not recruiting
- Last Updated
- 15 days ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
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.
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
Arms & Interventions
Phase 2: Lepetegravir + Lenacapavir pacfosacil (Treatment Group 1)
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.
Intervention: Lepetegravir
Phase 2: Lepetegravir + Lenacapavir pacfosacil (Treatment Group 1)
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.
Intervention: Lenacapavir pacfosacil
Phase 2 Extension Phase: Lepetegravir /Lenacapavir pacfosacil Fixed-dose Combination (FDC)
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.
Intervention: Lepetegravir/Lenacapavir pacfosacil FDC
Phase 3: Lepetegravir /Lenacapavir pacfosacil FDC + Placebo to Match (PTM) BVY (Treatment Group 1)
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.
Intervention: Placebo to Match BVY
Phase 3: Lepetegravir /Lenacapavir pacfosacil FDC + Placebo to Match (PTM) BVY (Treatment Group 1)
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.
Intervention: Lepetegravir/Lenacapavir pacfosacil FDC
Phase 3: BVY Placebo to Match Lepetegravir /Lenacapavir pacfosacil FDC + BVY (Treatment Group 2)
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.
Intervention: Bictegravir/emtricitabine/tenofovir alafenamide
Phase 3: BVY Placebo to Match Lepetegravir /Lenacapavir pacfosacil FDC + BVY (Treatment Group 2)
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.
Intervention: Placebo to Match GS1720/GS-4182 FDC
Phase 3 Extension Phase: Lepetegravir/Lenacapavir pacfosacil Fixed-dose Combination (FDC)
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.
Intervention: Lepetegravir/Lenacapavir pacfosacil FDC
Phase 2: Bictegravir/emtricitabine/tenofovir alafenamide (BVY) (Treatment Group 2)
Participants who have been virologically suppressed on bictegravir/emtricitabine/tenofovir alafenamide (BVY) will continue receiving BVY daily for at least 48 weeks.
Intervention: Bictegravir/emtricitabine/tenofovir alafenamide
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: Change From Baseline in CD4+ T-cell Count at Week 24(Baseline, Week 24)
- Phase 2: Proportion of Participants With HIV-1 RNA < 50 Copies/mL at Week 12 as Determined by the US FDA-defined Snapshot Algorithm(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(Week 48)
- Phase 2: Percentage of Participants Experiencing TEAEs Through Week 24(First dose date up to Week 24)
- Phase 2: Change From Baseline in Clusters of Differentiation 4 (CD4+) T-cell Count at Week 12(Baseline, Week 12)
- Phase 3: Proportion of Participants With HIV-1 RNA ≥ 50 copies/mL at Week 96 as Determined by the US FDA-defined Snapshot Algorithm(Week 96)
- Phase 2: Proportion of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 as Determined by the US FDA-defined Snapshot Algorithm(Week 24)
- Phase 2: Change From Baseline in CD4+ T-cell Count at Week 48(Baseline, Week 48)
- Phase 2: Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities Through Week 12(First dose date up to Week 12)
- Phase 2: PK Parameter: Ctau of GS-1720 and LEN(Day 1 up to Week 48)
- Phase 2: PK Parameter: AUCtau of GS-1720 and LEN(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(Week 96)
- Phase 3: Change From Baseline in CD4+ T-cell Count at Week 48(Baseline, Week 48)
- Phase 3: Percentage of Participants Experiencing TEAEs Through Week 48(First dose date up to 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(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(Week 48)
- Phase 2: Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities Through Week 24(First dose date up to Week 24)
- Phase 2: Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities Through Week 48(First dose date up to Week 48)
- Phase 2: Pharmacokinetic (PK) Parameter: Cmax of GS-1720 and Lenacapavir (LEN)(Day 1 up to Week 48)
- Phase 3: Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities Through Week 96(First dose date up to Week 96)
- Phase 2: Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs) Through Week 12(First dose date up to Week 12)
- Phase 2: Percentage of Participants Experiencing TEAEs Through Week 48(First dose date up to Week 48)
- Phase 2: PK Parameter: Tmax of GS-1720 and LEN(Day 1 up to Week 48)
- Phase 3: Proportion of Participants With HIV-1 RNA < 50 copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm(Week 48)
- Phase 3: Change From Baseline in CD4+ T-cell Count at Week 96(Baseline, Week 96)
- Phase 3: Proportion of Participants Experiencing TEAEs Through Week 96(First dose date up to Week 96)
- Phase 3: Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities Through Week 48(First dose date up to Week 48)
- Phase 2: Pharmacokinetic (PK) Parameter: Cmax of Lepetegravir and Lenacapavir (LEN)(Day 1 up to Week 48)
- Phase 2: PK Parameter: Tmax of Lepetegravir and LEN(Day 1 up to Week 48)
- Phase 2: PK Parameter: Ctau of Lepetegravir and LEN(Day 1 up to Week 48)
- Phase 2: PK Parameter: AUCtau of Lepetegravir and LEN(Day 1 up to Week 48)