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

Gilead Sciences

Status and phase: Enrolling; Phase 2

Conditions: Pre-Exposure Prophylaxis of HIV Infection

Treatments: Drug: Lenacapavir Tablet; Drug: Lenacapavir Injection; Drug: Emtricitabine/tenofovir disoproxil fumarate (F/TDF)

Study type: Interventional

Funder types: Industry

Identifiers

NCT06513312

GS-US-528-6727

2023-507891-31 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 262 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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262 participants in 4 patient groups

Randomized Phase: Lenacapavir (LEN) Group

Experimental group

Description:

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

Treatment:

Drug: Lenacapavir Injection

Drug: Lenacapavir Tablet

Randomized Phase: F/TDF

Active Comparator group

Description:

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

Treatment:

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

LEN Open Label Extension (OLE) Phase

Experimental group

Description:

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.

Treatment:

Drug: Lenacapavir Injection

Drug: Lenacapavir Tablet

Pharmacokinetic (PK) Tail Phase: F/TDF

Experimental group

Description:

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

Treatment:

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