Study to Assess Safety and Efficacy of Lenacapavir and Emtricitabine/Tenofovir Alafenamide for Pre-Exposure Prophylaxis in Adolescent Girls and Young Women at Risk of HIV Infection

Overview

The primary objective of this study is to evaluate the efficacy of lenacapavir (LEN) and emtricitabine/tenofovir alafenamide (F/TAF) in preventing the risk of human immunodeficiency virus (HIV) infection relative to the background HIV 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 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 Coverage Phase. The primary objective for the Incidence Phase of this study is to estimate the HIV background incidence rate. The primary objectives of the Randomized Phase of this study are to evaluate the efficacy of LEN and F/TAF for HIV pre-exposure prophylaxis (PrEP) in adolescent girls and young women (AGYW) at risk of HIV infection.

Full Title of Study: “A Phase 3, Double-Blinded, Multicenter, Randomized Study to Evaluate Safety and Efficacy of Twice Yearly Long-Acting Subcutaneous Lenacapavir, and Daily Oral Emtricitabine/Tenofovir Alafenamide for Pre-Exposure Prophylaxis in Adolescent Girls and Young Women at Risk of HIV Infection”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Prevention
    • Masking: Double (Participant, Investigator)
  • Study Primary Completion Date: March 2024

Interventions

  • Drug: Oral Lenacapavir (LEN)
    • Tablets administered orally without regard to food
  • Drug: Subcutaneous (SC) Lenacapavir (LEN)
    • Administered via SC injections
  • Drug: F/TAF
    • Tablets administered orally
  • Drug: F/TDF
    • Tablets administered orally
  • Drug: Placebo SC LEN
    • Administered via SC injections
  • Drug: PTM Oral LEN
    • Tablets administered orally
  • Drug: PTM F/TAF
    • Tablets administered orally
  • Drug: PTM F/TDF
    • Tablets administered orally

Arms, Groups and Cohorts

  • Experimental: Blinded Phase: LEN + Placebo-to-match (PTM) F/TAF
    • Participants will receive the following for at least 52 weeks: Subcutaneous (SC) lenacapavir (LEN) 927 mg every 26 weeks Oral PTM Emtricitabine/Tenofovir Alafenamide (F/TAF) once daily Oral LEN 600 mg on Days 1 and 2
  • Experimental: Blinded Phase: LEN + PTM F/TDF
    • Participants will receive the following for at least 52 weeks: SC 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
  • Experimental: Blinded Phase: Placebo LEN + F/TAF
    • Participants will receive the following for at least 52 weeks: SC placebo LEN every 26 weeks Oral F/TAF 200/25 mg once daily Oral PTM LEN on Days 1 and 2
  • Experimental: Blinded Phase: Placebo LEN + F/TDF
    • Participants will receive the following for at least 52 weeks: SC placebo LEN every 26 weeks Oral F/TDF 200/300 mg once daily Oral PTM LEN on Days 1 and 2
  • 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/TAF or F/TDF will receive SC LEN 927 mg on OLE Day 1 and OLE Week 26, and will also receive oral LEN 600 mg on OLE Days 1 and 2.
  • Experimental: Pharmacokinetic (PK) Tail Coverage Phase
    • At the completion of the LEN OLE phase, participants will transition into the PK Tail Coverage phase. Additionally, participants that either prematurely discontinue the study drug during the blinded phase or choose not to continue in the LEN OLE phase (if randomized to LEN in the blinded phase) or who discontinue the study drug in the LEN OLE phase are also eligible to transition to the PK Tail Coverage phase. Participants will receive oral F/TDF once daily for 78 weeks beginning 26 weeks after the last LEN injection.

Clinical Trial Outcome Measures

Primary Measures

  • Incidence Phase: Background HIV Incidence Reported Per 100-Person-Years (PY)
    • Time Frame: At Screening
  • Randomized Phase: HIV Incidence Reported Per 100-PY of Follow-up
    • Time Frame: When all participants have a minimum of 52 weeks of exposure to study drug or permanent discontinuation, whichever occurs first (maximum approximately 3 years)

Secondary Measures

  • HIV Incidence Among Participants While Adherent to Study Drug
    • Time Frame: When all participants have a minimum of 52 weeks of exposure to study drug or permanent discontinuation, whichever occurs first (maximum approximately 3 years)
  • Percentage of Participants Experiencing Treatment-Emergent Adverse Events
    • Time Frame: When all participants have a minimum of 52 weeks of exposure to study drug or permanent discontinuation, whichever occurs first (maximum approximately 3 years)
  • Percentage of Participants Experiencing Clinically Significant Laboratory Abnormalities
    • Time Frame: When all participants have a minimum of 52 weeks of exposure to study drug or permanent discontinuation, whichever occurs first (maximum approximately 3 years)

Participating in This Clinical Trial

Key Inclusion Criteria:

  • Incidence Phase – HIV-1 status unknown at initial screening and no prior human immunodeficiency virus ( HIV)-1 testing within the last 3 months – Sexually active (has had > 1 vaginal intercourse within the last 3 months) with cisgender male individuals (CGM) – Randomized Phase – Negative fourth generation HIV-1 antibody (Ab)/antigen (Ag) test confirmed with central HIV-1 testing – Estimated glomerular filtration rate (GFR) ≥ 60 mL/min at screening – Body weight ≥ 35 kg Key Exclusion Criteria:

  • Prior receipt of an HIV vaccine – Prior use of long-acting systemic pre-exposure prophylaxis (PrEP) Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Gender Eligibility: Female

Cisgender Female

Minimum Age: 16 Years

Maximum Age: 25 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • Gilead Sciences
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Gilead Study Director, Study Director, Gilead Sciences
  • Overall Contact(s)
    • Gilead Clinical Study Information Center, 1-833-445-3230 (GILEAD-0), GileadClinicalTrials@gilead.com

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