Study of Lenacapavir Taken Twice a Year for HIV Pre-Exposure Prophylaxis (PrEP)

NCT06513312 | Active Not Recruiting Phase 2 FDA Drug

• 2 other identifiers: GS-US-528-67272023-507891-31
• Study Type: interventional
• Target: 268
• Locations: 2 countries
• Sites: 14

Brief Summary

The goals of this clinical study are to learn more about the study drug lenacapavir (LEN), by comparing the consistent and continuous use of LEN and emtricitabine/tenofovir disoproxil fumarate (coformulated; Truvada®) (F/TDF), then by observing the safety of LEN and F/TDF, evaluating the acceptability of LEN injections and oral F/TDF, and observe how LEN moves throughout the body in people who would benefit from pre-exposure prophylaxis (PrEP). The primary objective of this study is to compare LEN and F/TDF consistent and continuous use among people who would benefit from PrEP.

Conditions

Pre-Exposure Prophylaxis of HIV Infection

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants with LEN and F/TDF Persistence through 52 Weeks

  This outcome measure will compare LEN and F/TDF persistence through 52 weeks, where persistence is defined by On-time LEN Injection at Day 1/Baseline and Week 26 and On-time Follow-up Visit at Week 52 for LEN arm and by Adherence Levels Based on tenofovir diphosphate (TFV-DP) concentrations in red blood cells consistent with ≥ 4 doses/week (≥ 700 fmol/punch) in dried blood spot (DBS) at Weeks 13, 26, 39, and 52 for F/TDF arm.

  Up to Week 52

Secondary Outcomes (5)

• Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)

  First dose date up to 30 days post last dose at Week 78

• Percentage of Participants Experiencing Treatment-emergent Clinical Laboratory Abnormalities

  First dose date up to 30 days post last dose at Week 78

• Overall acceptability of LEN and F/TDF as PrEP as Assessed by Percentage of Participants with responses to Question on Acceptability

  Up to Week 52

• Pharmacokinetic (PK) Parameter: Ctrough for LEN at Week 26

  Week 26

• PK Parameter: Ctrough for LEN at Week 52

  Week 52

Study Arms (4)

Randomized Phase: Lenacapavir (LEN) Group

EXPERIMENTAL

Participants will receive subcutaneous (SC) LEN 927 mg on Day 1 and 26 weeks and oral LEN 600 mg on Day 1 and 2.

Drug: Lenacapavir Injection; Drug: Lenacapavir Tablet

Randomized Phase: F/TDF

ACTIVE COMPARATOR

Participants will receive daily F/TDF (200/300 mg) fixed dose combination (FDC) tablets for up to 52 weeks.

Drug: Emtricitabine/tenofovir disoproxil fumarate (F/TDF)

LEN Open Label Extension (OLE) Phase

EXPERIMENTAL

Participants in the F/TDF group will transition to get LEN and participants in the LEN group will continue to get LEN. All participants will get SC LEN on Day 1 and week 26 of the OLE phase.

Drug: Lenacapavir Injection; Drug: Lenacapavir Tablet

Pharmacokinetic (PK) Tail Phase: F/TDF

EXPERIMENTAL

After completion of the LEN OLE Phase or upon discontinuation from the Randomized Phase for those receiving LEN, participants will be transitioned to receive F/TDF in the PK Tail Phase. Participants will receive once daily F/TDF for 78 weeks, beginning 26 weeks after the last LEN injection

Drug: Emtricitabine/tenofovir disoproxil fumarate (F/TDF)

Interventions

Lenacapavir Injection DRUG

Administered subcutaneously

Also known as: GS-6207, Yeztugo®

LEN Open Label Extension (OLE) Phase; Randomized Phase: Lenacapavir (LEN) Group

Lenacapavir Tablet DRUG

Administered orally

Also known as: GS-6207

LEN Open Label Extension (OLE) Phase; Randomized Phase: Lenacapavir (LEN) Group

Emtricitabine/tenofovir disoproxil fumarate (F/TDF) DRUG

Administered orally

Also known as: Truvada®

Pharmacokinetic (PK) Tail Phase: F/TDF; Randomized Phase: F/TDF

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Cisgender male, Cisgender female, Transgender male, Transgender female, and Gender non-binary
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to comprehend and provide a signed written informed consent, which must be obtained prior to initiation of study procedures.
• Cisgender men who have sex with men, transgender women, transgender men, cisgender women, and nonbinary people.
• Increased likelihood of HIV acquisition as indicated by at least one of the following:
• Condomless sex with ≥ 2 partners in the past 6 months
• Diagnosis of a bacterial sexually transmitted infection (STI) in the past 12 months
• Engagement in sex work or transactional sex in the past 12 months
• Use of ≥ 2 courses of nonoccupational HIV post-exposure prophylaxis (nPEP) in the past 12 months
• Condomless sex with a partner living with HIV who has unknown or unsuppressed viral load (≥ 200 copies/mL) in the past 12 months
• Negative local rapid HIV-1/2 antibody (Ab)/antigen (Ag) test, central HIV-1/2 Ab/Ag, and HIV-1 RNA quantitative nucleic acid amplification testing (NAAT) at screening.
• \) If rapid HIV-1/2 Ab/Ag tests are unavailable due to extenuating circumstances, sites may run a laboratory-instrumented HIV-1/2 Ab/Ag test at their local laboratory, only if they confirm this is a fourth-generation assay and the time from blood draw to injection at any injection visit is \< 48 hours.
• Estimated glomerular filtration rate (GFR) at least 60 mL/min at screening according to the Cockcroft-Gault formula for creatinine clearance (CLcr):
• (140 - age in years) × (weight in kg) x (0.85 if female) = CLcr (mL/min) / 72 × (serum creatinine in mg/dL)

You may not qualify if:

• Coenrollment in any other clinical study (including observational) without prior approval from the sponsor is prohibited while participating in this study.
• Known hypersensitivity to the study drug, the metabolites, or formulation excipient.
• Current use of PrEP, defined as the use of PrEP in the preceding 4 weeks. PrEP should not be discontinued to facilitate study participation. For cabotegravir, this is defined as 4 weeks since the next injection was due (ie, 12 weeks since their most recent cabotegravir injection).
• Current use of nPEP, unless the prescribed course will be completed prior to randomization.
• Past or current participation in HIV vaccine or HIV broadly neutralizing Ab study unless participant provides documentation of receipt of placebo (ie, not active product).
• Acute viral hepatitis A, B, or C or evidence of chronic hepatitis B or C infection
• Severe hepatic impairment or a history of or current clinical decompensated liver cirrhosis (eg, ascites, encephalopathy, variceal bleeding).
• Have a suspected or known active, serious infection(s) (eg, active tuberculosis, etc).

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (14)

Hopital Avicenne

Bobigny, 93000, France

Location

Hopital Europeen Marseille

Marseille, 13006, France

Location

CHU Nice Archet

Nice, 6202, France

Location

Hopital Saint Louis - Assistance Publique des Hopitaux de Paris

Paris, 75010, France

Location

APHP Hopital Saint-Antoine

Paris, 75012, France

Location

APHP Bichat Claude-Bernard Hospital

Paris, 75018, France

Location

University Hospitals Birmingham NHS Foundation Trust, Birmingham Heartlands Hospital

Birmingham, B9 5SS, United Kingdom

Location

Clinical Research Facility, University Hospitals Sussex NHS Foundation Trust

Brighton, BN2 3EW, United Kingdom

Location

Axess Sexual Health, Liverpool University Hospitals NHS Trust

Liverpool, L7 8YE, United Kingdom

Location

Grahame Hayton Unit, Ambrose King Centre, Royal London Hospital, Barts Health NHS Trust

London, E11BB, United Kingdom

Location

Homerton Healthcare NHS Foundation Trust, Homerton University Hospital

London, E9 6SR, United Kingdom

Location

Caldecot Centre, Kings College Hospital, Kings College Hospital NHS Foundation Trust

London, SE5 9RS, United Kingdom

Location

Chelsea and Westminster Hospital NHS Foundation Trust, Clinical Research Facility, Chelsea and Westminster Hospital

London, SW10 9NH, United Kingdom

Location

Manchester University NS Foundation Trust

Manchester, M13 0FH, United Kingdom

Location

Related Links

• Gilead Clinical Trials Website

MeSH Terms

Interventions

lenacapavir; Emtricitabine; Tenofovir; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2024
• First Posted: July 22, 2024
• Study Start: October 7, 2024
• Primary Completion: May 1, 2026
• Study Completion (Estimated): December 1, 2028
• Last Updated: September 2, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

FR (6); GB (8)