Study of Oral Weekly GS-1720 and GS-4182 Compared With Biktarvy in People With HIV-1 Who Have Not Been Treated
- Conditions
- HIV-1-infection
- Interventions
- Drug: Bictegravir/emtricitabine/tenofovir alafenamideDrug: GS-1720/GS-4182 FDCDrug: Placebo to Match BVYDrug: Placebo to Match GS1720/GS-4182 FDC
- Registration Number
- NCT06613685
- Lead Sponsor
- Gilead Sciences
- Brief Summary
The goal of this clinical study is to learn more about the experimental drugs GS-1720 (an oral, long-acting integrase strand transfer inhibitor (INSTI)) and GS-4182 (a prodrug of Lenacapavir (LEN)); to compare the combination of GS-1720 and GS-4182 with the current standard-of-care treatment bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (Biktarvy), 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 in treatment-naive people with HIV-1 (PWH).
This study has two phases: Phase 2 and Phase 3.
The primary objectives of this study are:
Phase 2: To evaluate the efficacy of oral weekly GS-1720 coadministered with GS-4182 versus continuing Biktarvy (BVY) in treatment-naive PWH at Week 24.
Phase 3: To evaluate the efficacy of oral weekly GS-1720/GS-4182 fixed-dose combination (FDC) tablet regimen versus continuing BVY in treatment-naive PWH at Week 48.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 675
- HIV-1 RNA ≥ 500 copies/mL at screening.
- Antiretroviral (ARV) treatment-naive, except the use of oral pre-exposure prophylaxis (PrEP) or postexposure prophylaxis (PEP) with emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) or F/TAF, up to 1 month prior to screening.
Key
-
Prior use of any long acting parenteral antiretrovirals (ARVs) such as monoclonal antibodies, broadly neutralizing antibodies targeting HIV-1, LEN, injectable cabotegravir (including oral cabotegravir lead-in), and/or injectable rilpivirine.
-
Documented resistance to the integrase strand-transfer inhibitor class, specifically, resistance-associated mutations E92G/Q, G118R, F121Y, Y143C/H/R, S147G, Q148H/K/R, N155H/S, or R263K in the integrase gene.
-
Any of the following laboratory values at screening:
- CD4 cell count < 200 cells/mm3 at screening.
- Estimated glomerular filtrations arate < 60 mL/min according to the Modification of Diet in Renal Disease formula.
- Hepatic transaminases (aspartate aminotransferase and alanine aminotransferase) > 1.5 × upper limit of normal (ULN).
- Direct bilirubin > 1.5 × ULN.
- Platelets count < 50,000 cells/mm3.
- Hemoglobin < 8.0 g/dL.
-
Active or occult hepatitis B virus infection.
-
Active hepatitis C virus infection.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Phase 2: GS-1720 + GS-4182 (Treatment Group 1) GS-4182 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-1720 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: B/F/TAF (Treatment Group 2) Bictegravir/emtricitabine/tenofovir alafenamide Participants will receive B/F/TAF (50/200/25 mg) daily for at least 48 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 (650/300 mg) weekly. Phase 2 Treatment Group 2 will receive a loading dose of GS-1720/GS-4182 FDC (1300 mg/600 mg) on Extension Phase Day 1, then GS-1720/GS-4182 FDC (650/300 mg) 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) B/F/TAF (Treatment Group 1) GS-1720/GS-4182 FDC Participants will receive a 1-day loading dose of GS-1720/GS-4182 FDC on Day 1. Thereafter, participants will receive GS-1720/GS-4182 FDC tablets weekly + PTM B/F/TAF once daily. Participants will receive treatment for at least 96 weeks. Phase 3: GS-1720/GS-4182 FDC + Placebo to Match (PTM) B/F/TAF (Treatment Group 1) Placebo to Match BVY Participants will receive a 1-day loading dose of GS-1720/GS-4182 FDC on Day 1. Thereafter, participants will receive GS-1720/GS-4182 FDC tablets weekly + PTM B/F/TAF once daily. Participants will receive treatment for at least 96 weeks. Phase 3: B/F/TAF + PTM GS-1720/GS-4182 FDC (Treatment Group 2) Bictegravir/emtricitabine/tenofovir alafenamide Participants will receive oral B/F/TAF daily along with PTM GS-1720/GS-4182 FDC weekly for at least 96 weeks. Additionally, participants will receive a 1-day loading dose of PTM GS-1720/GS-4182 on Day 1. Phase 3: B/F/TAF + PTM GS-1720/GS-4182 FDC (Treatment Group 2) Placebo to Match GS1720/GS-4182 FDC Participants will receive oral B/F/TAF daily along with PTM GS-1720/GS-4182 FDC weekly for at least 96 weeks. Additionally, participants will receive a 1-day loading dose of PTM GS-1720/GS-4182 on Day 1. 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 continue to receive GS-1720/GS-4182 FDC weekly while PTM B/F/TAF will be discontinued. Phase 3 Treatment Group 2 will switch to receive GS-1720/GS-4182 FDC tablets weekly. Participants in Treatment Group 2 will also receive a 1-day loading dose of GS-1720/GS-4182 FDC on Extension Phase Day 1. Participants who choose to enter the Phase 3 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.
- 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: 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: Change From Baseline in log10 HIV-1 RNA at Week 12 Baseline, Week 12 Phase 2: Change From Baseline in log10 HIV-1 RNA at Week 24 Baseline, Week 24 Phase 2: Change From Baseline in log10 HIV-1 RNA at Week 48 Baseline, Week 48 Phase 2: Change From Baseline in Clusters of Differentiation 4 (CD4) Cell Count at Week 12 Baseline, Week 12 Phase 2: Change From Baseline in CD4 Cell Count at Week 24 Baseline, Week 24 Phase 2: Change From Baseline in CD4 Cell Count at Week 48 Baseline, Week 48 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 24 First dose date up to Week 24 Phase 2: Percentage of Participants Experiencing TEAEs Through Week 48 First dose date up to Week 48 Phase 2: Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities Through Week 12 First dose date up to Week 12 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), as Applicable Day 1 up to Week 24 Cmax is defined as the maximum observed concentration of drug.
Phase 2: PK Parameter: Tmax of GS-1720 and LEN, as Applicable Day 1 up to Week 24 Tmax is defined as the time (observed time point) of Cmax.
Phase 2: PK Parameter: Ctau of GS-1720 and LEN, as Applicable Day 1 up to Week 24 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, as Applicable Day 1 up to Week 24 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 log10 HIV-1 RNA at Week 48 Baseline, Week 48 Phase 3: Change From Baseline in log10 HIV-1 RNA at Week 96 Baseline, Week 96 Phase 3: Change From Baseline in CD4 Cell Count at Week 48 Baseline, Week 48 Phase 3: Change From Baseline in CD4 Cell Count at Week 96 Baseline, Week 96 Phase 3: Percentage of Participants Experiencing TEAEs Through Week 48 First dose date up to Week 48 Phase 3: Percentage 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 3: Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities Through Week 96 First dose date up to Week 96
Trial Locations
- Locations (52)
Hospital Clinico San Carlos
🇪🇸Madrid, Spain
Hospital Universitario Virgen de la Victoria
🇪🇸Malaga, Spain
Proyecto ACTU
🇵🇷San Juan, Puerto Rico
Hospital Universitario Alvaro Cunqueiro
🇪🇸Pontevedra, Spain
Unidade Local de Saúde de Santo António, E.P.E.
🇵🇹Porto, Portugal
Unidade Local de Saúde de São João E.P.E.
🇵🇹Porto, Portugal
UAB 1917 Research Clinic
🇺🇸Birmingham, Alabama, United States
The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
🇺🇸Torrance, California, United States
Mills Clinical Research
🇺🇸West Hollywood, California, United States
Georgetown University Medical School
🇺🇸Washington, District of Columbia, United States
Midland Florida Clinical Research Center, LLC
🇺🇸DeLand, Florida, United States
Midway Immunology and Research Center
🇺🇸Fort Pierce, Florida, United States
Floridian Clinical Research, LLC
🇺🇸Miami Lakes, Florida, United States
HOPE Clinical Research
🇵🇷San Juan, Puerto Rico
Orlando Immunology Center
🇺🇸Orlando, Florida, United States
Triple O Research Institute, P.A.
🇺🇸West Palm Beach, Florida, United States
Emory University Hospital Midtown Infectious Disease Clinic
🇺🇸Atlanta, Georgia, United States
Mercer University, Department of Internal Medicine
🇺🇸Macon, Georgia, United States
Saint Michael's Medical Center
🇺🇸Newark, New Jersey, United States
NYU Langone Health Vaccine Center
🇺🇸New York, New York, United States
Medical University of South Carolina (MUSC) Research Nexus
🇺🇸Charleston, South Carolina, United States
St Hope Foundation, Inc.
🇺🇸Bellaire, Texas, United States
Prism Health North Texas, Aids Arms
🇺🇸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
UT Health San Antonio
🇺🇸San Antonio, Texas, United States
MultiCare Rockwood Main Clinic
🇺🇸Spokane, Washington, United States
Clinique Médicale L'Actuel
🇨🇦Montreal, Canada
Ottawa Hospital Research Institute
🇨🇦Ottawa, Canada
Universitätsklinikum Bonn, Medizinische Klinik und Poliklinik I, Immunologische Studienambulanz
🇩🇪Bonn, Germany
Universitätsmedizin Essen, Universitätsklinikum Essen, Klinik für Dermatologie, Venerologie und Allergologie, HPSTD-Ambulanz
🇩🇪Essen, Germany
ICH Study Center GmbH & Co. KG
🇩🇪Hamburg, Germany
Medizinische Hochschule Hannover, Klinik für Rheumatologie und Immunologie, Gebäude K14
🇩🇪Hannover, Germany
Klinikum rechts der Isar, Technische Universität München, Klinik und Poliklinik für Innere Medizin II
🇩🇪Munchen, Germany
Wojewódzki Szpital Obserwacyjno-Zakaźny im. Tadeusza Browicza
🇵🇱Bydoszcz, Poland
Punkt Zdrowia
🇵🇱Gdansk, Poland
Unidade Local de Saude de Amadora Sinatra EPE, Hospital Prof. Doutor Fernando Fonseca
🇵🇹Amadora, Portugal
Unidade Local de Saúde de Lisboa Ocidental E.P.E. - Hospital Egas Moniz
🇵🇹Lisboa, Portugal
Unidade Local de Saúde de Santo Maria E.P.E. - Hospital Santa Maria
🇵🇹Lisboa, Portugal
Institutul National De Boli Infectioase Prof. Dr. Matei Bals
🇷🇴Bucharest, Romania
Spitalul Clinic De Urgenta Prof Dr Agrippa Ionescu
🇷🇴Bucharest, Romania
Spitalul Clinic De Boli Infectioase Cluj-Napoca
🇷🇴Cluj-Napoca, Romania
Spitalul Clinic de Boli Infectioase Constanta
🇷🇴Constanta, Romania
JOSHA Research
🇿🇦Bloemfontein, South Africa
FPD Ndevana Community Research Site
🇿🇦East London, South Africa
Synergy Biomed Research Institute
🇿🇦East London, South Africa
CRISMO Research Center
🇿🇦Germiston, South Africa
WITS RHI Research Centre
🇿🇦Johannesburg, South Africa
Clinical Research Institute of South Africa (CRISA)
🇿🇦KwaZulu-Natal, South Africa
The Aurum Institute Tembisa Clinic 4
🇿🇦Tembisa, South Africa
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Hospital Arnau de Vilanova de Valencia
🇪🇸Valencia, Spain