A Study of GS-3242 in Combination With Lenacapavir Versus Biktarvy in Virologically Suppressed People With HIV-1

A Phase 2 Randomized, Active-Controlled Study Evaluating the Safety and Efficacy of an Injectable Regimen of GS-3242 in Combination With Lenacapavir Versus Biktarvy (Bictegravir/Emtricitabine/Tenofovir Alafenamide) in Virologically Suppressed People With HIV-1

The study will have two parts: Part A and Part B. In Part A, the goal of the study is to compare the effectiveness of switching to the study drugs GS-3242 plus Lenacapavir (LEN) versus continuing Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF)), in virologically suppressed people with HIV-1 (PWH) in treatment Group 1, 2 and 3 at Week 35. In Part B the goal of the study is to compare the effectiveness of switching to the study drugs, GS-3242 and LEN versus continuing B/F/TAF in Groups 4 and 3 at Week 26.

The primary objective of part A is to evaluate the efficacy of switching to intramuscular (IM) GS-3242 plus IM LEN versus continuing on B/F/TAF PWH who are virologically suppressed in treatment Groups 1, 2, and 3 at Week 35 and Part B is to evaluate the efficacy of switching to IM GS-3242 plus IM LEN versus continuing on B/F/TAF in PWH who are virologically suppressed in Treatment Groups 4 and 3 at Week 26.

Study Overview

• Status: Not yet recruiting
• Conditions: HIV-1-infection
• Intervention / Treatment: Drug: B/F/TAF; Drug: Lenacapavir Tablet; Drug: GS-3242 Tablet; Drug: GS-3242 Injection; Drug: Lenacapavir Injection

• Study Type: Interventional
• Enrollment (Estimated): 175
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Gilead Clinical Study Information Center; Phone Number: 1-833-445-3230 (GILEAD-0); Email: GileadClinicalTrials@gilead.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Documented human immunodeficiency virus type 1 (HIV-1) ribonucleic acid (RNA) < 50 copies/mL for ≥ 6 months before screening.
• Plasma HIV-1 RNA levels < 50 copies/mL at screening.
• Receiving bictegravir/emtricitabine/tenofovir alafenamide (coformulated; Biktarvy®) (B/F/TAF) for ≥ 6 months prior to screening.
• No documented resistance to GS-3242 (integrase mutation Q148H/K/R plus at least 2 of the following integrase mutations: L74I/M, T97A, E138A/K/T, or G140A/C/S).

Key Exclusion Criteria:

• Prior use of, or exposure to GS-3242 or LEN.
• History of virologic failure while on an integrase strand transfer inhibitor (INSTI)-based regimen.
• Prior use of any long-acting parenteral antiretroviral therapy (ART) medications such as monoclonal antibodies or broadly neutralizing antibodies targeting HIV-1, injectable cabotegravir (including oral cabotegravir lead-in), or injectable rilpivirine.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: Group 1 of GS-3242 + LEN; Participants will be randomized to receive oral loading doses of GS-3242 in combination with LEN oral tablets, followed by intramuscular (IM) injections of GS-3242 and LEN up to 52 weeks.	Drug: Lenacapavir Tablet; Administered orally; Other Names: LEN; Drug: GS-3242 Tablet; Administered orally; Drug: GS-3242 Injection; Administered intramuscularly (IM); Drug: Lenacapavir Injection; Administered IM; Other Names: LEN
Experimental: Part A: Group 2 of GS-3242 + LEN; Participants will be randomized to receive oral loading doses of GS-3242 in combination with LEN oral tablets, followed by a IM injections of GS-3242 (at a different dose than Group 1) and LEN up to 52 weeks.	Drug: Lenacapavir Tablet; Administered orally; Other Names: LEN; Drug: GS-3242 Tablet; Administered orally; Drug: GS-3242 Injection; Administered intramuscularly (IM); Drug: Lenacapavir Injection; Administered IM; Other Names: LEN
Experimental: Part A: Group 3 of B/F/TAF; Participants will be randomized to continue to receive 50/200/25 mg of B/F/TAF daily for up to 52 weeks.	Drug: B/F/TAF; Administered orally
Experimental: Part B: Group 4 (Conditional) of GS-3242 + LEN; Participants will be enrolled (non-randomized) to receive oral loading doses of GS-3242 in combination with LEN oral tablets, followed IM injection of GS-3242 and LEN (at different doses than Groups 1 and 2) up to 52 weeks.	Drug: Lenacapavir Tablet; Administered orally; Other Names: LEN; Drug: GS-3242 Tablet; Administered orally; Drug: GS-3242 Injection; Administered intramuscularly (IM); Drug: Lenacapavir Injection; Administered IM; Other Names: LEN

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Part A: Proportion of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 35 as Determined by the United States (US) Food and Drug Administration (FDA) Snapshot Algorithm	Week 35
Part B: Proportion of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 26 as Determined by the US FDA Snapshot Algorithm	Week 26

Secondary Outcome Measures

Outcome Measure	Time Frame
Part A and Part B: Proportion of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 52 as Determined by the US FDA Snapshot Algorithm	Week 52
Part A: Proportion of Participants With HIV-1 RNA < 50 Copies/mL at Week 35 as Determined by the US FDA Snapshot Algorithm	Week 35
Part A and Part B: Proportion of Participants With HIV-1 RNA < 50 Copies/mL at Week 52 as Determined by the US FDA Snapshot Algorithm	Week 52
Part A: Change From Baseline in Clusters of Differentiation 4 (CD4) Cell Count at Week 35	Baseline, Week 35
Part A and Part B: Change From Baseline in Clusters of Differentiation 4 (CD4) Cell Count at Week 52	Baseline, Week 52
Part B: Proportion of Participants Wth HIV-1 RNA < 50 Copies/mL at Week 26 as Determined by the US FDA Snapshot Algorithm	Week 26
Part B: Change From Baseline in CD4 Cell Count at Week 26	Baseline, Week 26
Part A: Percentage of Participants Experiencing Treatment-Emergent Adverse Events (AEs) Through Week 35	Up to Week 35
Part A and Part B: Percentage of Participants Experiencing Treatment-Emergent Adverse Events (AEs) Through Week 52	Up to Week 52
Part B: Percentage of Participants Experiencing Treatment-Emergent AEs Through Week 26	Up to Week 26
Part A: Group 1 and 2:Trough Concentrations of GS-3242 and LEN at Week 18	Week 18
Part A: Group 1 and 2:Trough Concentrations of GS-3242 and LEN at Week 35	Week 35
Part A: Group 1 and 2 and Part B: Groups 1 and 2:Trough Concentrations of GS-3242 and LEN at Week 52	Week 52
Part B: Trough Concentrations at GS-3242 and LEN at Week 26	Week 26

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Investigators: Study Director: Gilead Study Director, Gilead Sciences

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): April 1, 2033

Study Registration Dates

• First Submitted: June 8, 2026
• First Submitted That Met QC Criteria: June 8, 2026
• First Posted (Actual): June 12, 2026

Study Record Updates

• Last Update Posted (Actual): June 12, 2026
• Last Update Submitted That Met QC Criteria: June 8, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: lenacapavir
• Other Study ID Numbers: GS-US-643-7710

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No