NCT06613685|TerminatedPhase 2DMCFDA Drug

Study Stopped

Sponsor decision to terminate study.

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

WONDERS2

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

Gilead Sciences ClinicalTrials.gov

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2 other identifiers

GS-US-695-71562024-512505-66

Study Type

interventional

Target

Locations

9 countries

Sites

Timeline

RegisteredSep 2024

StartedOct 2024

CompletionMar 2026

Brief 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.

Trial Health

Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

participants targeted

Target at P50-P75 for phase_2

Timeline

Completed

Started Oct 2024

Shorter than P25 for phase_2

Geographic Reach

9 countries

58 active sites

Status

terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

1.4 years study duration

First Submitted

Initial submission to the registry

September 23, 2024

Completed

3 days until next milestone

First Posted

Study publicly available on registry

September 26, 2024

Completed

25 days until next milestone

Study Start

First participant enrolled

October 21, 2024

Completed

1.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 16, 2026

Completed

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 16, 2026

Completed

Last Updated

April 15, 2026

Status Verified

April 1, 2026

Enrollment Period

1.4 years

First QC Date

September 23, 2024

Last Update Submit

April 10, 2026

Conditions

HIV-1-infection

Outcome Measures

Primary Outcomes (2)

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 Outcomes (27)

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
+22 more secondary outcomes

Study Arms (6)

Phase 2: Lepetegravir + Lenacapavir Pacfosacil (Treatment Group 1)

EXPERIMENTAL

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.

Drug: lepetegravirDrug: lenacapavir pacfosacil

Phase 2: B/F/TAF (Treatment Group 2)

ACTIVE COMPARATOR

Participants will receive B/F/TAF (50/200/25 mg) daily for at least 48 weeks.

Drug: Bictegravir/emtricitabine/tenofovir alafenamide

Phase 2 Extension Phase: Lepetegravir/Lenacapavir Pacfosacil Fixed-dose Combination (FDC)

EXPERIMENTAL

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 (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.

Drug: lepetegravir/lenacapavir pacfosacil FDC

Phase 3: Lepetegravir/Lenacapavir Pacfosacil FDC + Placebo to Match B/F/TAF (Treatment Group 1)

EXPERIMENTAL

Participants 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.

Drug: lepetegravir/lenacapavir pacfosacil FDCDrug: Placebo to Match BVY

Phase 3: B/F/TAF + PTM lepetegravir/Lenacapavir Pacfosacil FDC (Treatment Group 2)

ACTIVE COMPARATOR

Participants 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.

Drug: Bictegravir/emtricitabine/tenofovir alafenamideDrug: Placebo to Match GS1720/GS-4182 FDC

Phase 3 Extension Phase: Lepetegravir/Lenacapavir Pacfosacil Fixed-dose Combination (FDC)

EXPERIMENTAL

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 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.

Drug: lepetegravir/lenacapavir pacfosacil FDC