Study of Lenacapavir Taken Twice a Year for HIV Pre-Exposure Prophylaxis (PrEP) (PURPOSE 5)

A Phase 2, Open-label, Multicenter, Randomized Study to Evaluate the Persistence, Safety, Acceptability, and Pharmacokinetics of Twice Yearly Long-acting Subcutaneous Lenacapavir for HIV Pre-Exposure Prophylaxis (PrEP) in People Who Would Benefit From PrEP

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Pre-Exposure Prophylaxis of HIV Infection
• Intervention / Treatment: Drug: Lenacapavir Tablet; Drug: Lenacapavir Injection; Drug: Emtricitabine/tenofovir disoproxil fumarate (F/TDF)

• Study Type: Interventional
• Enrollment (Actual): 268
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Bobigny, France, 93000
    • Hopital Avicenne
  • Marseille, France, 13006
    • Hôpital Européen Marseille
  • Nice, France, 6202
    • CHU Nice Archet
  • Paris, France, 75012
    • APHP Hopital Saint-Antoine
  • Paris, France, 75010
    • Hopital Saint Louis - Assistance Publique des Hopitaux de Paris
  • Paris, France, 75018
    • APHP Bichat Claude-Bernard Hospital
• United Kingdom
  • Birmingham, United Kingdom, B9 5SS
    • University Hospitals Birmingham NHS Foundation Trust, Birmingham Heartlands Hospital
  • Brighton, United Kingdom, BN2 3EW
    • Clinical Research Facility, University Hospitals Sussex NHS Foundation Trust
  • Liverpool, United Kingdom, L7 8YE
    • Axess Sexual Health, Liverpool University Hospitals NHS Trust
  • London, United Kingdom, E11BB
    • Grahame Hayton Unit, Ambrose King Centre, Royal London Hospital, Barts Health NHS Trust
  • London, United Kingdom, E9 6SR
    • Homerton Healthcare NHS Foundation Trust, Homerton University Hospital
  • London, United Kingdom, SE5 9RS
    • Caldecot Centre, Kings College Hospital, Kings College Hospital NHS Foundation Trust
  • London, United Kingdom, SW10 9NH
    • Chelsea and Westminster Hospital NHS Foundation Trust, Clinical Research Facility, Chelsea and Westminster Hospital
  • Manchester, United Kingdom, M13 0FH
    • Manchester University NS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Key Inclusion Criteria:

• 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:

  1. Condomless sex with ≥ 2 partners in the past 6 months
  2. Diagnosis of a bacterial sexually transmitted infection (STI) in the past 12 months
  3. Engagement in sex work or transactional sex in the past 12 months
  4. Use of ≥ 2 courses of nonoccupational HIV post-exposure prophylaxis (nPEP) in the past 12 months
  5. 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.

  1) 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)

Key Exclusion Criteria:

• 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).

Note: Other protocol defined Inclusion/Exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Randomized Phase: Lenacapavir (LEN) Group; 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 Tablet; Administered orally; Other Names: GS-6207; Drug: Lenacapavir Injection; Administered subcutaneously; Other Names: GS-6207; Yeztugo®
Experimental: LEN Open Label Extension (OLE) Phase; 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 Tablet; Administered orally; Other Names: GS-6207; Drug: Lenacapavir Injection; Administered subcutaneously; Other Names: GS-6207; Yeztugo®
Experimental: Pharmacokinetic (PK) Tail Phase: F/TDF; 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); Administered orally; Other Names: Truvada®
Active Comparator: Randomized Phase: F/TDF; 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); Administered orally; Other Names: Truvada®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	To assess the acceptability of the study drug, participants will complete the questionnaire including a question on general acceptability of the assigned study drug on an ordinal 5-category scale with a response of: Completely unacceptable, Unacceptable, No opinion, Acceptable, or Completely acceptable.	Up to Week 52
Pharmacokinetic (PK) Parameter: Ctrough for LEN at Week 26	Ctrough is defined as the concentration at the end of the dosing interval.	Week 26
PK Parameter: Ctrough for LEN at Week 52	Ctrough is defined as the concentration at the end of the dosing interval.	Week 52

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• Gilead Clinical Trials Website

Study record dates

Study Major Dates

• Study Start (Actual): October 7, 2024
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): November 1, 2028

Study Registration Dates

• First Submitted: July 16, 2024
• First Submitted That Met QC Criteria: July 16, 2024
• First Posted (Actual): July 22, 2024

Study Record Updates

• Last Update Posted (Actual): May 19, 2026
• Last Update Submitted That Met QC Criteria: May 15, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Blood-Borne Infections; Urogenital Diseases; Genital Diseases; Immune System Diseases; Infections; RNA Virus Infections; Virus Diseases; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; HIV Infections; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pharmaceutical Preparations; Nucleic Acids, Nucleotides, and Nucleosides; Purines; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Organophosphorus Compounds; Nucleosides; Deoxyribonucleosides; Organophosphonates; Adenine; Drug Combinations; Tenofovir; Emtricitabine; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; lenacapavir
• Other Study ID Numbers: GS-US-528-6727; 2023-507891-31 (Other Identifier: EU CT Number)

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
• product manufactured in and exported from the U.S.: Yes