Study of Lenacapavir for HIV Pre-Exposure Prophylaxis in People Who Are at Risk for HIV Infection (PURPOSE 2)

Gilead Sciences

Status and phase: Active, not recruiting; Phase 3

Conditions: Pre-Exposure Prophylaxis of HIV Infection

Treatments: Drug: Sub-cutaneous (SC) Lenacapavir (LEN); Drug: PTM Oral LEN; Drug: Oral Lenacapavir (LEN); Drug: Placebo SC LEN; Drug: F/TDF; Drug: F/TAF (for US participants only); Drug: PTM F/TDF

Study type: Interventional

Funder types: Industry

Identifiers

NCT04925752

GS-US-528-9023

DOH-27-102021-6681 (Other Identifier)

Details and patient eligibility

About

The goal of this study is to evaluate the efficacy of the study drugs, lenacapavir (LEN) in preventing HIV infection, in participants ≥ 16 years of age who have condomless receptive anal sex with partners assigned male at birth and are at risk for HIV-1 infection.

The primary objective of this study is to evaluate the efficacy of LEN for HIV-1 PrEP in participants ≥ 16 years of age who have condomless receptive anal sex with partners assigned male at birth at risk of HIV-1 infection.

Enrollment: 3,292 patients

Sex: All

Ages: 16+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

Incidence Phase

• CGM, TGW, TGM, and GNB who have condomless receptive anal sex with partners assigned male at birth and are at risk for HIV infection.

• HIV-1 status unknown at screening and no prior HIV-1 testing within the last 3 months.

• Sexually active with ≥ 1 partner assigned male at birth (condomless receptive anal sex) in the last 12 months and 1 of the following:

  • Condomless receptive anal sex with ≥ 2 partners in the last 12 weeks.
  • History of syphilis, rectal gonorrhea, or rectal chlamydia in the last 24 weeks.
  • Self-reported use of stimulants with sex in the last 12 weeks.

Randomized Phase

• Negative local rapid fourth generation HIV-1/2 Ab/Ag, central fourth generation HIV-1/2 Ab/Ag, and HIV-1 RNA quantitative nucleic acid amplification testing (NAAT).
• Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min at screening according to the Cockcroft-Gault formula for creatinine clearance (CLcr).

Key Exclusion Criteria:

Incidence Phase

• Prior use of HIV PrEP (including F/TDF or F/TAF) or HIV postexposure prophylaxis (PEP) in the past 12 weeks or any prior use of long-acting systemic PrEP (including cabotegravir or islatravir).
• Prior recipient of an HIV vaccine or HIV broadly neutralizing antibody formulation.

Randomized Phase

• 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.

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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3,292 participants in 4 patient groups

Randomized Blinded Phase: LEN + Placebo-to-match (PTM) F/TDF

Experimental group

Description:

Participants will receive the following for up to approximately 52 weeks: * Subcutaneous (SC) lenacapavir (LEN) 927 mg every 26 weeks * Oral PTM Emtricitabine/Tenofovir Disoproxil Fumarate (F/TDF) once daily * Oral LEN 600 mg on Days 1 and 2 Participants will receive oral LEN if SC injections are not available.

Treatment:

Drug: Oral Lenacapavir (LEN)

Drug: Sub-cutaneous (SC) Lenacapavir (LEN)

Drug: PTM F/TDF

Randomized Blinded Phase: Placebo LEN + F/TDF

Experimental group

Description:

Participants will receive the following for up to approximately 52 weeks: * SC LEN placebo every 26 weeks * Oral F/TDF 200/300 mg once daily * PTM Oral LEN on Days 1 and 2 Participants will receive oral LEN placebo if SC injections are not available.

Treatment:

Drug: PTM Oral LEN

Drug: Placebo SC LEN

Drug: F/TDF

LEN Open-Label Extension (OLE) Phase

Experimental group

Description:

Participants will be offered entry into LEN OLE Phase, following completion of primary analysis, if LEN demonstrates acceptable safety and efficacy in the Randomized Blinded Phase. Participants randomized to LEN will continue to receive SC LEN 927 mg, every 26 weeks (± 7 days), and have study visits every 13 weeks (± 7 days). Participants randomized to F/TDF will switch to SC LEN 927 mg on OLE Day 1, Week 26 and every 26 weeks thereafter. Participants will also receive oral LEN 600 mg on OLE Days 1 and 2. All participants in LEN OLE Phase will complete the phase, once LEN becomes available or the sponsor decides to discontinue the study, whichever happens first. After completing LEN OLE Phase or study discontinuation, participants will transition to local PrEP, including LEN or other options. If a participant exits early, they will complete an early study drug discontinuation (ESDD), be referred to local PrEP services if needed, and have a 30-day follow-up visit.

Treatment:

Drug: Oral Lenacapavir (LEN)

Drug: Sub-cutaneous (SC) Lenacapavir (LEN)

Pharmacokinetic (PK) Tail Phase

Experimental group

Description:

Participants who prematurely discontinue study drug during the Randomized Blinded Phase and participants that were randomized to LEN who choose not to continue in the LEN OLE Phase will transition to the PK Tail Phase. Participants will receive oral F/TDF (or Emtricitabine/Tenofovir Alafenamide (F/TAF) for US participants only) once daily for 78 weeks to cover the PK tail and complete visits every 13 weeks (+/- 7 days). Upon unblinding, participants who were randomized to F/TDF in the Randomized Blinded Phase who decline to participate in the LEN OLE Phase will complete the ESDD visit, transition to local HIV prevention services, and return for a 30-day follow-up visit.

Treatment:

Drug: F/TAF (for US participants only)

Drug: F/TDF