Study of Oral Weekly GS-1720 and GS-4182 Versus Biktarvy in People With HIV-1 Who Are Virologically Suppressed
- Conditions
- HIV-1-Infection
- Interventions
- Drug: GS-1720/GS-4182 FDCDrug: Bictegravir/emtricitabine/tenofovir alafenamideDrug: Placebo to Match BVYDrug: Placebo to Match GS1720/GS-4182 FDC
- Registration Number
- NCT06544733
- Lead Sponsor
- Gilead Sciences
- Brief Summary
The goal of this clinical study is to learn more about the experimental drugs GS-1720 and GS-4182; to compare the combination of GS-1720 and GS-4182 with the current standard-of-care treatment bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF, BVY), 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.
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 GS-1720 in combination with GS-4182 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 GS-1720/GS-4182 Fixed-dose combination (FDC) tablet regimen versus continuing BVY in virologically suppressed PWH at Week 48.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 675
- Documented plasma HIV-1 RNA < 50 copies/mL for ≥ 24 weeks before and at screening.
- Receiving BVY for ≥ 24 weeks prior to screening.
Key
-
Prior use of, or exposure to LEN, GS-1720, or GS-4182.
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History of virologic failure while on an integrase strand-transfer inhibitor (INSTI)-based regimen.
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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.
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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.
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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
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Active or occult hepatitis B virus (HBV) infection.
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Active hepatitis C virus (HCV).
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Phase 3: BVY Placebo to Match GS-1720/GS-4182 FDC + BVY (Treatment Group 2) Placebo to Match GS1720/GS-4182 FDC 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 GS-1720/GS-4182 on Day 1 and weekly PTM thereafter. Participants will receive treatment for at least 96 weeks. Phase 2 Extension Phase: GS-1720/GS-4182 Fixed-dose Combination (FDC) GS-1720/GS-4182 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 GS-1720/GS-4182 FDC weekly. Phase 2 Treatment Group 2 will receive a loading dose of GS-1720/GS-4182 FDC on Extension Phase Day 1 then, GS-1720/GS-4182 FDC 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. Phase 3: GS-1720/GS-4182 FDC + Placebo to Match (PTM) BVY (Treatment Group 1) GS-1720/GS-4182 FDC Participants who have been virologically suppressed on BVY will switch from BVY to GS-1720/GS-4182 FDC tablets weekly + placebo-to-match (PTM) BVY once daily. In addition, participants will receive a 1-day loading dose regimen of GS-1720/GS-4182 FDC on Day 1. Participants will receive treatment for at least 96 weeks. Phase 2: Bictegravir/emtricitabine/tenofovir alafenamide (BVY) (Treatment Group 2) Bictegravir/emtricitabine/tenofovir alafenamide Participants who have been virologically suppressed on bictegravir/emtricitabine/tenofovir alafenamide (BVY) will continue receiving BVY daily for at least 48 weeks. Phase 3: BVY Placebo to Match GS-1720/GS-4182 FDC + BVY (Treatment Group 2) Bictegravir/emtricitabine/tenofovir alafenamide 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 GS-1720/GS-4182 on Day 1 and weekly PTM thereafter. Participants will receive treatment for at least 96 weeks. Phase 3: GS-1720/GS-4182 FDC + Placebo to Match (PTM) BVY (Treatment Group 1) Placebo to Match BVY Participants who have been virologically suppressed on BVY will switch from BVY to GS-1720/GS-4182 FDC tablets weekly + placebo-to-match (PTM) BVY once daily. In addition, participants will receive a 1-day loading dose regimen of GS-1720/GS-4182 FDC on Day 1. Participants will receive treatment for at least 96 weeks. Phase 3 Extension Phase: GS-1720/GS-4182 Fixed-dose Combination (FDC) GS-1720/GS-4182 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 GS-1720/GS-4182 FDC weekly. Phase 3 Treatment Group 2 will receive a 1-day loading dose of GS-1720/GS-4182 FDC on Extension Phase Day 1, then GS-1720/GS-4182 FDC 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. Phase 2: GS-1720 + GS-4182 (Treatment Group 1) GS-1720 Participants who have been virologically suppressed on bictegravir/emtricitabine/tenofovir alafenamide (BVY) will switch to GS-1720 (650 mg tablet) and GS-4182 (300 mg tablet) coadministered. 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. Phase 2: GS-1720 + GS-4182 (Treatment Group 1) GS-4182 Participants who have been virologically suppressed on bictegravir/emtricitabine/tenofovir alafenamide (BVY) will switch to GS-1720 (650 mg tablet) and GS-4182 (300 mg tablet) coadministered. 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.
- Primary Outcome Measures
Name Time Method 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 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 Week 48
- Secondary Outcome Measures
Name Time Method 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 Ctau is defined as the observed drug concentration at the end of the dosing interval.
Phase 2: PK Parameter: AUCtau of GS-1720 and LEN Day 1 up to Week 48 AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
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 Cmax is defined as the maximum observed concentration of drug.
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 Tmax is defined as the time (observed time point) of Cmax.
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
Trial Locations
- Locations (37)
UAB 1917 Research Clinic
🇺🇸Birmingham, Alabama, United States
Pacific Oaks Medical Group
🇺🇸Beverly Hills, California, United States
Be Well Medical Center
🇺🇸Berkley, Michigan, United States
Ruane Clinical Research Group
🇺🇸Los Angeles, California, United States
Mills Clinical Research
🇺🇸Los Angeles, California, United States
BIOS Clinical Research
🇺🇸Palm Springs, California, United States
UCSF Division of HIV, Infectious Diseases & Global Medicine
🇺🇸San Francisco, California, United States
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
🇺🇸Torrance, California, United States
Georgetown University Medical Center
🇺🇸Washington, District of Columbia, United States
Midland Florida Clinical Research Center, LLC
🇺🇸DeLand, Florida, United States
CAN Community Health
🇺🇸Sarasota, Florida, United States
Midway and Immunology Research Center
🇺🇸Fort Pierce, Florida, United States
Floridian Clinical Research
🇺🇸Miami Lakes, Florida, United States
AIDS Healthcare Foundation - The Kinder Medical Group
🇺🇸Miami, Florida, United States
Orlando Immunology Center
🇺🇸Orlando, Florida, United States
Triple O Research Institute, P.A.
🇺🇸West Palm Beach, Florida, United States
Metro Infectious Disease Consultants, P.L.L.C.
🇺🇸Decatur, Georgia, United States
Mercer University, Department of Internal Medicine
🇺🇸Macon, Georgia, United States
Chatham County Health Department
🇺🇸Savannah, Georgia, United States
KC CARE Health Center
🇺🇸Kansas City, Missouri, United States
Saint Michael's Medical Center
🇺🇸Newark, New Jersey, United States
AXCES Research Group, LLC
🇺🇸El Paso, Texas, United States
NewYork-Presbyterian Queens
🇺🇸Flushing, New York, United States
NYU Langone Health Vaccine Center
🇺🇸New York, New York, United States
Rosedale Health and Wellness
🇺🇸Huntersville, North Carolina, United States
Central Texas Clinical Research
🇺🇸Austin, Texas, United States
St Hope Foundation, Inc.
🇺🇸Bellaire, Texas, United States
Prism Health North Texas, Oak Cliff Health Center
🇺🇸Dallas, Texas, United States
North Texas Infectious Diseases Consultants, PA
🇺🇸Dallas, Texas, United States
Texas Centers for Infectious Disease Associates
🇺🇸Fort Worth, Texas, United States
The Crofoot Research Center, INC.
🇺🇸Houston, Texas, United States
DCOL Center for Clinical Research
🇺🇸Longview, Texas, United States
Peter Shalit, MD
🇺🇸Seattle, Washington, United States
Centro Ararat, Inc.
🇵🇷San Juan, Puerto Rico
Clinical Research Puerto Rico
🇵🇷San Juan, Puerto Rico
HOPE Clinical Research
🇵🇷San Juan, Puerto Rico
Proyecto ACTC
🇵🇷San Juan, Puerto Rico