LAST UPDATED
April 15, 2026
Clinicaltrials.gov ID
CTSID
OVERVIEW
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 Treatment-Naive People With HIV-1 (WONDERS2)
PROTOCOL SUMMARY
The goal of this clinical study is to learn more about the experimental drugs lepetegravir (formerly GS-1720) (an oral, long-acting integrase strand transfer inhibitor (INSTI)) and lenacapavir pacfosacil (formerly GS-4182) (a prodrug of Lenacapavir (LEN)); to compare the combination of lepetegravir and lenacapavir pacfosacil with the current standard-of-care treatment bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (Biktarvy), 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 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 lepetegravir coadministered with lenacapavir pacfosacil versus continuing Biktarvy (BVY) in treatment-naive PWH at Week 24. Phase 3: To evaluate the efficacy of oral weekly lepetegravir/lenacapavir pacfosacil fixed-dose combination (FDC) tablet regimen versus continuing BVY in treatment-naive PWH at Week 48.
View moreParticipation requirements
Age
18 years +
Sex
All
Healthy Volunteers
No
Age
18 years +
Sex
All
Healthy Volunteers
No
Study details
Medical Condition
HIV-1-infection
Gender
N/A
Date
October 2024 - March 2026
Study Type
Interventional
Study Phase
Phase 2, Phase 3
Product
lepetegravir, lenacapavir pacfosacil, Bictegravir/emtricitabine/tenofovir alafenamide, lepetegravir/lenacapavir pacfosacil FDC, Placebo to Match BVY, Placebo to Match GS1720/GS-4182 FDC
Eligibility information
Inclusion criteria
- 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.
Exclusion criteria
- 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:
- 1. CD4 cell count < 200 cells/mm3 at screening.
- 2. Estimated glomerular filtrations arate < 60 mL/min according to the Modification of Diet in Renal Disease formula.
- 3. Hepatic transaminases (aspartate aminotransferase and alanine aminotransferase) > 1.5 × upper limit of normal (ULN).
- 4. Direct bilirubin > 1.5 × ULN.
- 5. Platelets count < 50,000 cells/mm3.
- 6. 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.
Locations
Locations (58)
The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Torrance, California, United States, 90502
Mills Clinical Research
West Hollywood, California, United States, 90046
Georgetown University Medical School
Washington D.C., District of Columbia, United States, 20007
Midland Florida Clinical Research Center, LLC
DeLand, Florida, United States, 32720
Midway Immunology and Research Center
Ft. Pierce, Florida, United States, 34982
Floridian Clinical Research, LLC
Miami Lakes, Florida, United States, 33016
Triple O Research Institute, P.A.
West Palm Beach, Florida, United States, 33407
Emory University Hospital Midtown Infectious Disease Clinic
Atlanta, Georgia, United States, 30308
Mercer University, Department of Internal Medicine
Macon, Georgia, United States, 31201
University of Mississippi Medical Center
Jackson, Mississippi, United States, 39216
Saint Michael's Medical Center
Newark, New Jersey, United States, 07102
NYU Langone Health Vaccine Center
New York, New York, United States, 10016
Medical University of South Carolina (MUSC) Research Nexus
Charleston, South Carolina, United States, 29425
Prism Health North Texas, Aids Arms
Dallas, Texas, United States, 75208
North Texas Infectious Diseases Consultants, PA
Dallas, Texas, United States, 75246
Texas Centers for Infectious Disease Associates
Fort Worth, Texas, United States, 76104
MultiCare Rockwood Main Clinic
Spokane, Washington, United States, 99202
Chronic Viral Illness Service / McGill University Health Centre
Montreal, Canada, H4A 3J1
Universitätsklinikum Bonn, Medizinische Klinik und Poliklinik I, Immunologische Studienambulanz
Bonn, Germany, 53127
Universitätsmedizin Essen, Universitätsklinikum Essen, Klinik für Dermatologie, Venerologie und Allergologie, HPSTD-Ambulanz
Essen, Germany, 45122
Medizinische Hochschule Hannover, Klinik für Rheumatologie und Immunologie, Gebäude K14
Hanover, Germany, 30625
Klinikum rechts der Isar, Technische Universität München, Klinik und Poliklinik für Innere Medizin II
München, Germany, 81675
Wojewódzki Szpital Obserwacyjno-Zakaźny im. Tadeusza Browicza
Bydoszcz, Poland, 85-030
Samodzielny Publiczny Wojewódzki Szpital Zespolony w Szczecinie
Szczecin, Poland, 71-455
Unidade Local de Saude de Amadora Sinatra EPE, Hospital Prof. Doutor Fernando Fonseca
Amadora, Portugal, 2720- 276
Unidade Local de Saúde de Lisboa Ocidental E.P.E. - Hospital Egas Moniz
Lisbon, Portugal, 1249-019
Unidade Local de Saúde de Santo Maria E.P.E. - Hospital Santa Maria
Lisbon, Portugal, 1649-035
Unidade Local de Saúde de Santo António, E.P.E.
Porto, Portugal, 4050
Institutul National De Boli Infectioase Prof. Dr. Matei Bals
Bucharest, Romania, 021105
Spitalul Clinic De Urgenta Prof Dr Agrippa Ionescu
Bucharest, Romania,
Spitalul Clinic De Boli Infectioase Cluj-Napoca
Cluj-Napoca, Romania, 400003
Spitalul Clinic de Boli Infectioase Constanta
Constanța, Romania, 00709
Clinical Hospital of Infectious Diseases and Pneumophysiology Dr. Victor Babes Timisoara
Timișoara, Romania,
Durban International Clinical Research Site, Enhancing Care Foundation
Durban, South Africa, 4013
Clinical Research Institute of South Africa (CRISA)
KwaZulu-Natal, South Africa, 4449
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