Purpose

The primary objective of this study is to evaluate the efficacy of lenacapavir (LEN) in preventing the risk of human immunodeficiency virus (HIV) - 1 infection relative to the background HIV-1 incidence rate. The study will be conducted in 2 parts: a cross-sectional study (Incidence Phase) and a double-blind, randomized study (Randomized Phase). The Incidence Phase will include initial assessments that will provide an estimate of the concurrent background HIV-1 incidence rate. The Randomized Phase of the study will have a Blinded Phase, a LEN Open-label Extension (OLE) Phase, and a pharmacokinetic (PK) Tail Phase. The primary objective for the Incidence Phase of this study is to estimate the HIV-1 background incidence rate. The primary objective of the Randomized Blinded Phase of this study is to evaluate the efficacy of lenacapavir for HIV-1 pre-exposure prophylaxis (PrEP) in cisgender men (CGM), transgender women (TGW), transgender men (TGM), and gender nonbinary people (GNB) ≥ 16 years of age who have condomless receptive anal sex with partners assigned male at birth and are at risk for HIV-1 infection.

Condition

Eligibility

Eligible Ages
Over 16 Years
Eligible Genders
All
Accepts Healthy Volunteers
Yes

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)

Exclusion Criteria

Incidence Phase - Prior use of oral PrEP (including F/TDF or F/TAF) 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.

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Double (Participant, Investigator)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Blinded Phase: LEN + Placebo-to-match (PTM) F/TDF
Participants will receive the following for at least 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
  • Drug: Oral Lenacapavir (LEN)
    Tablets administered orally without regard to food
    Other names:
    • GS-6207
  • Drug: Sub-cutaneous (SC) Lenacapavir (LEN)
    Administered via SC injections
    Other names:
    • GS-6207
  • Drug: PTM F/TDF
    Tablets administered orally
Experimental
Blinded Phase: Placebo LEN + F/TDF
Participants will receive the following for at least 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
  • Drug: F/TDF
    Tablets administered orally
    Other names:
    • Truvada®
  • Drug: Placebo SC LEN
    Administered via SC injections
  • Drug: PTM Oral LEN
    Tablets administered orally
Experimental
LEN Open-Label Extension (OLE) Phase
After completion of the Blinded phase, participants will be offered entry into the LEN OLE Phase. Participants randomized to LEN will continue to receive SC LEN 927 mg every 26 weeks for a total of 2 doses. Participants randomized to F/TDF will receive SC LEN 927 mg on OLE Day 1, OLE Week 26, and will also receive oral LEN 600 mg on OLE Days 1 and 2.
  • Drug: Oral Lenacapavir (LEN)
    Tablets administered orally without regard to food
    Other names:
    • GS-6207
  • Drug: Sub-cutaneous (SC) Lenacapavir (LEN)
    Administered via SC injections
    Other names:
    • GS-6207
Experimental
PK Tail Phase
At the completion of the LEN OLE phase, participants will transition into the PK Tail phase. Additionally, participants that prematurely discontinue the study drug during blinded phase and participants that were randomized to LEN who choose not to continue in the LEN OLE Phase are also eligible to 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 beginning 26 weeks after the last injection of LEN.
  • Drug: F/TDF
    Tablets administered orally
    Other names:
    • Truvada®
  • Drug: F/TAF (for US participants only)
    F/TAF tablets administered orally once daily

Recruiting Locations

Howard Brown Health Center
Chicago, Illinois 60613

More Details

Status
Recruiting
Sponsor
Gilead Sciences

Study Contact

Gilead Clinical Study Information Center
1-833-445-3230 (GILEAD-0)
GileadClinicalTrials@gilead.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.