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HIV-1-infectionPhase 2/3WONDERS2NCT06613685

Study of Oral Weekly GS-1720 and GS-4182 Compared With Biktarvy in People With HIV-1 Who Have Not Been Treated

A Phase 2/3 study testing lepetegravir, lenacapavir pacfosacil and Bictegravir/emtricitabine/tenofovir alafenamide in people with HIV-1-infection, run by Gilead Sciences at 58 sites in 9 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
HIV-1-infection
What is being tested?
lepetegravir, lenacapavir pacfosacil and Bictegravir/emtricitabine/tenofovir alafenamide
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
73 participants
Where
58 sitesin 9 countries
Study dates
21 Oct 2024to 16 Mar 2026
Phase
Phase 2/3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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).
Show all 12Show fewer
  • 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.

Trial locations and contacts

58 sites in 9 countries.

58 sites in 9 countries

United States21 sites

  • Emory University Hospital Midtown Infectious Disease Clinic

    Atlanta, Georgia, 30308

  • St Hope Foundation, Inc.

    Bellaire, Texas, 77401

  • UAB 1917 Research Clinic

    Birmingham, Alabama, 35222

  • Medical University of South Carolina (MUSC) Research Nexus

    Charleston, South Carolina, 29425

  • Prism Health North Texas, Aids Arms

    Dallas, Texas, 75208

  • North Texas Infectious Diseases Consultants, PA

    Dallas, Texas, 75246

  • Midland Florida Clinical Research Center, LLC

    DeLand, Florida, 32720

  • Texas Centers for Infectious Disease Associates

    Fort Worth, Texas, 76104

  • Midway Immunology and Research Center

    Ft. Pierce, Florida, 34982

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216

  • Mercer University, Department of Internal Medicine

    Macon, Georgia, 31201

  • Floridian Clinical Research, LLC

    Miami Lakes, Florida, 33016

  • NYU Langone Health Vaccine Center

    New York, New York, 10016

  • Saint Michael's Medical Center

    Newark, New Jersey, 07102

  • Orlando Immunology Center

    Orlando, Florida, 32803

  • UT Health San Antonio

    San Antonio, Texas, 78229

  • MultiCare Rockwood Main Clinic

    Spokane, Washington, 99202

  • The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

    Torrance, California, 90502

  • Georgetown University Medical School

    Washington D.C., District of Columbia, 20007

  • Mills Clinical Research

    West Hollywood, California, 90046

  • Triple O Research Institute, P.A.

    West Palm Beach, Florida, 33407

Other trials in United States

South Africa8 sites

  • JOSHA Research

    Bloemfontein, 9301

  • Durban International Clinical Research Site, Enhancing Care Foundation

    Durban, 4013

  • Synergy Biomed Research Institute

    East London, 5241

  • CRISMO Research Center

    Germiston, 1401

  • WITS RHI Research Centre

    Johannesburg, 2038

  • Clinical Research Institute of South Africa (CRISA)

    KwaZulu-Natal, 4449

  • FPD Ndevana Community Research Site

    Ndevana, 5660

  • The Aurum Institute Tembisa Clinic 4

    Tembisa, 1632

Other trials in South Africa

Spain6 sites

  • Hospital Clinic de Barcelona

    Barcelona, 8036

  • Hospital Clinico San Carlos

    Madrid, 28040

  • Hospital Universitario Fundación Jiménez Díaz

    Madrid, 28040

  • Hospital Universitario Virgen de la Victoria

    Málaga, 29010

  • Hospital Universitario Alvaro Cunqueiro

    Pontevedra, 36312

  • Hospital Arnau de Vilanova de Valencia

    Valencia, 46015

Other trials in Spain

Germany5 sites

  • Universitätsklinikum Bonn, Medizinische Klinik und Poliklinik I, Immunologische Studienambulanz

    Bonn, 53127

  • Universitätsmedizin Essen, Universitätsklinikum Essen, Klinik für Dermatologie, Venerologie und Allergologie, HPSTD-Ambulanz

    Essen, 45122

  • ICH Study Center GmbH & Co. KG

    Hamburg, 20146

  • Medizinische Hochschule Hannover, Klinik für Rheumatologie und Immunologie, Gebäude K14

    Hanover, 30625

  • Klinikum rechts der Isar, Technische Universität München, Klinik und Poliklinik für Innere Medizin II

    München, 81675

Other trials in Germany

Portugal5 sites

  • Unidade Local de Saude de Amadora Sinatra EPE, Hospital Prof. Doutor Fernando Fonseca

    Amadora, 2720- 276

  • Unidade Local de Saúde de Lisboa Ocidental E.P.E. - Hospital Egas Moniz

    Lisbon, 1249-019

  • Unidade Local de Saúde de Santo Maria E.P.E. - Hospital Santa Maria

    Lisbon, 1649-035

  • Unidade Local de Saúde de Santo António, E.P.E.

    Porto, 4050

  • Unidade Local de Saúde de São João E.P.E.

    Porto, 4200-319

Other trials in Portugal

Romania5 sites

  • Institutul National De Boli Infectioase Prof. Dr. Matei Bals

    Bucharest, 021105

  • Spitalul Clinic De Urgenta Prof Dr Agrippa Ionescu

    Bucharest

  • Spitalul Clinic De Boli Infectioase Cluj-Napoca

    Cluj-Napoca, 400003

  • Spitalul Clinic de Boli Infectioase Constanta

    Constanța, 00709

  • Clinical Hospital of Infectious Diseases and Pneumophysiology Dr. Victor Babes Timisoara

    Timișoara

Other trials in Romania

Canada3 sites

  • Clinique Médicale L'Actuel

    Montreal, H2L 4P9

  • Chronic Viral Illness Service / McGill University Health Centre

    Montreal, H4A 3J1

  • Ottawa Hospital Research Institute

    Ottawa, K1H 8L6

Other trials in Canada

Poland3 sites

  • Wojewódzki Szpital Obserwacyjno-Zakaźny im. Tadeusza Browicza

    Bydoszcz, 85-030

  • Punkt Zdrowia

    Gdansk, 80-172

  • Samodzielny Publiczny Wojewódzki Szpital Zespolony w Szczecinie

    Szczecin, 71-455

Other trials in Poland

Puerto Rico2 sites

  • HOPE Clinical Research

    San Juan, PR, 00909

  • Proyecto ACTU

    San Juan, PR, 00935

Other trials in Puerto Rico

About this study

Official title: 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

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.

Read more

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.

Conditions
HIV-1-infection
Being tested
lepetegravir, lenacapavir pacfosacil, Bictegravir/emtricitabine/tenofovir alafenamide, lepetegravir/lenacapavir pacfosacil FDC, Placebo to Match BVY

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • lepetegravirDrug

    Also called GS-1720

    Tablets administered orally without regard to food

  • lenacapavir pacfosacilDrug

    Also called GS-4182

    Tablets administered orally without regard to food

  • Bictegravir/emtricitabine/tenofovir alafenamideDrug

    Also called Biktarvy ®

    Tablets administered orally without regard to food

  • lepetegravir/lenacapavir pacfosacil FDCDrug

    Also called GS-1720/GS-4182

    Tablets administered orally without regard to food

  • Placebo to Match BVYDrug

    Tablets administered orally without regard to food

  • Placebo to Match GS1720/GS-4182 FDCDrug

    Tablets administered orally without regard to food

Study groups in NCT06613685
Study groupRoleWhat they receive
Phase 2: Lepetegravir + Lenacapavir Pacfosacil (Treatment Group 1)ExperimentalParticipants 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.
Receives: Drug: lepetegravir; Drug: lenacapavir pacfosacil
Phase 2: B/F/TAF (Treatment Group 2)Active comparatorParticipants will receive B/F/TAF (50/200/25 mg) daily for at least 48 weeks.
Receives: Drug: Bictegravir/emtricitabine/tenofovir alafenamide
Phase 2 Extension Phase: Lepetegravir/Lenacapavir Pacfosacil Fixed-dose Combination (FDC)ExperimentalAt 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 (650/300 mg) weekly. Phase 2 Treatment Group 2 will receive a loading dose of lepetegravir/lenacapavir pacfosacil FDC (1300 mg/600 mg) on Extension Phase Day 1, then lepetegravir/lenacapavir pacfosacil FDC (650/300 mg) 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.
Receives: Drug: lepetegravir/lenacapavir pacfosacil FDC
Phase 3: Lepetegravir/Lenacapavir Pacfosacil FDC + Placebo to Match B/F/TAF (Treatment Group 1)ExperimentalParticipants will receive a 1-day loading dose of lepetegravir/lenacapavir pacfosacil FDC on Day 1. Thereafter, participants will receive lepetegravir/lenacapavir pacfosacil FDC tablets weekly + placebo to match (PTM) B/F/TAF once daily. Participants will receive treatment for at least 96 weeks.
Receives: Drug: lepetegravir/lenacapavir pacfosacil FDC; Drug: Placebo to Match BVY
Phase 3: B/F/TAF + PTM lepetegravir/Lenacapavir Pacfosacil FDC (Treatment Group 2)Active comparatorParticipants will receive oral B/F/TAF daily along with PTM lepetegravir/lenacapavir pacfosacil FDC weekly for at least 96 weeks. Additionally, participants will receive a 1-day loading dose of PTM lepetegravir/lenacapavir pacfosacil on Day 1.
Receives: Drug: Bictegravir/emtricitabine/tenofovir alafenamide; Drug: Placebo to Match GS1720/GS-4182 FDC
Phase 3 Extension Phase: Lepetegravir/Lenacapavir Pacfosacil Fixed-dose Combination (FDC)ExperimentalAfter 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 lepetegravir/lenacapavir pacfosacil FDC weekly while PTM B/F/TAF will be discontinued. Phase 3 Treatment Group 2 will switch to receive lepetegravir/lenacapavir pacfosacil FDC tablets weekly. Participants in Treatment Group 2 will also receive a 1-day loading dose of lepetegravir/lenacapavir pacfosacil FDC on Extension Phase Day 1. Participants who choose to enter the Phase 3 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.
Receives: Drug: lepetegravir/lenacapavir pacfosacil FDC

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: Week 24

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

    Measured: Week 48

Secondary outcomes (27)

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

    Measured: Week 12

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

    Measured: Week 48

  3. Phase 2: Change From Baseline in log10 HIV-1 RNA at Week 12

    Measured: Baseline, Week 12

  4. Phase 2: Change From Baseline in log10 HIV-1 RNA at Week 24

    Measured: Baseline, Week 24

  5. Phase 2: Change From Baseline in log10 HIV-1 RNA at Week 48

    Measured: Baseline, Week 48

  6. Phase 2: Change From Baseline in Clusters of Differentiation 4 (CD4) Cell Count at Week 12

    Measured: Baseline, Week 12

  7. Phase 2: Change From Baseline in CD4 Cell Count at Week 24

    Measured: Baseline, Week 24

  8. Phase 2: Change From Baseline in CD4 Cell Count at Week 48

    Measured: Baseline, Week 48

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

    Measured: First dose date up to Week 12

  10. Phase 2: Percentage of Participants Experiencing TEAEs Through Week 24

    Measured: First dose date up to Week 24

  11. Phase 2: Percentage of Participants Experiencing TEAEs Through Week 48

    Measured: First dose date up to Week 48

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

    Measured: First dose date up to Week 12

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

    Measured: First dose date up to Week 24

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

    Measured: First dose date up to Week 48

  15. Phase 2: Pharmacokinetic (PK) Parameter: Cmax of Lepetegravir and Lenacapavir (LEN), as Applicable

    Cmax is defined as the maximum observed concentration of drug.

    Measured: Day 1 up to Week 24

  16. Phase 2: PK Parameter: Tmax of Lepetegravir and LEN, as Applicable

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

    Measured: Day 1 up to Week 24

  17. Phase 2: PK Parameter: Ctau of Lepetegravir and LEN, as Applicable

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

    Measured: Day 1 up to Week 24

  18. Phase 2: PK Parameter: AUCtau of Lepetegravir and LEN, as Applicable

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

    Measured: Day 1 up to Week 24

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

    Measured: Week 96

  20. Phase 3: Change From Baseline in log10 HIV-1 RNA at Week 48

    Measured: Baseline, Week 48

  21. Phase 3: Change From Baseline in log10 HIV-1 RNA at Week 96

    Measured: Baseline, Week 96

  22. Phase 3: Change From Baseline in CD4 Cell Count at Week 48

    Measured: Baseline, Week 48

  23. Phase 3: Change From Baseline in CD4 Cell Count at Week 96

    Measured: Baseline, Week 96

  24. Phase 3: Percentage of Participants Experiencing TEAEs Through Week 48

    Measured: First dose date up to Week 48

  25. Phase 3: Percentage of Participants Experiencing TEAEs Through Week 96

    Measured: First dose date up to Week 96

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

    Measured: First dose date up to Week 48

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

    Measured: First dose date up to Week 96

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Sep 2024
  2. Study start21 Oct 2024
  3. Primary completion16 Mar 2026
  4. Study completion16 Mar 2026

Why it stopped: Sponsor decision to terminate study.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
73 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06613685
Sponsor's protocol ID
GS-US-695-7156
Other IDs
2024-512505-66
Acronym
WONDERS2
Status last verified
Apr 2026
First submitted
23 Sep 2024
Last updated
15 Apr 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing lepetegravir, lenacapavir pacfosacil and Bictegravir/emtricitabine/tenofovir alafenamide in people with HIV-1-infection, run by Gilead Sciences at 58 sites in 9 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 15 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 58 sites in United States, South Africa, Spain, Germany, Portugal and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Sponsor decision to terminate study.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06613685.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Apr 2026.

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