Pre-Exposure Prophylaxis Study of Lenacapavir and Emtricitabine/Tenofovir Alafenamide in Adolescent Girls and Young Women at Risk of HIV Infection (PURPOSE 1)

• ClinicalTrials.gov Identifier: NCT04994509
• Recruitment Status: Active, not recruiting
• First Posted: August 6, 2021
• Last Update Posted: February 28, 2024
• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

Tracking Information

• First Submitted Date: August 2, 2021
• First Posted Date: August 6, 2021
• Last Update Posted Date: February 28, 2024
• Actual Study Start Date: August 30, 2021
• Estimated Primary Completion Date: September 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 2, 2021)

• 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) ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 2, 2021)

• 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) ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Pre-Exposure Prophylaxis Study of Lenacapavir and Emtricitabine/Tenofovir Alafenamide in Adolescent Girls and Young Women at Risk of HIV Infection
• Official Title: 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
• Brief Summary: The goal of this study is to evaluate the efficacy in preventing HIV infection of the study drugs, lenacapavir (LEN) and emtricitabine/tenofovir alafenamide (F/TAF), in adolescent girls and young women.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Prevention
• Condition: Pre-Exposure Prophylaxis of HIV Infection

Intervention

• Drug: Oral Lenacapavir (LEN)
  Tablets administered orally without regard to food
  Other Name: GS-6207
• Drug: Subcutaneous (SC) Lenacapavir (LEN)
  Administered via SC injections
  Other Name: GS-6207
• Drug: F/TAF
  Tablets administered orally
  Other Name: Descovy®
• Drug: F/TDF
  Tablets administered orally
  Other Name: Truvada®
• 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

Study Arms

• 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
  Interventions:

  • Drug: Oral Lenacapavir (LEN)
  • Drug: Subcutaneous (SC) Lenacapavir (LEN)
  • Drug: PTM F/TAF
• 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
  Interventions:

  • Drug: Oral Lenacapavir (LEN)
  • Drug: Subcutaneous (SC) Lenacapavir (LEN)
  • Drug: PTM F/TDF
• 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
  Interventions:

  • Drug: F/TAF
  • Drug: Placebo SC LEN
  • Drug: PTM Oral LEN
• 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
  Interventions:

  • Drug: F/TDF
  • Drug: Placebo SC LEN
  • Drug: PTM Oral LEN
• 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.

  Interventions:

  • Drug: Oral Lenacapavir (LEN)
  • Drug: Subcutaneous (SC) Lenacapavir (LEN)
• 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.

  Intervention: Drug: F/TDF

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: February 26, 2024): 5368
• Original Estimated Enrollment (submitted: August 2, 2021): 5010
• Estimated Study Completion Date: July 2027
• Estimated Primary Completion Date: September 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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 HIV pre-exposure prophylaxis (PrEP) or or HIV PEP (postexposure prophylaxis).

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

Sex/Gender

• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Cisgender Female

• Ages: 16 Years to 25 Years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: South Africa, Uganda

Administrative Information

• NCT Number: NCT04994509
• Other Study ID Numbers: GS-US-412-5624; DOH-27- 072021-6125 ( Registry Identifier: South African National Clinical Trial Registry )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Gilead Sciences
• Original Responsible Party: Same as current
• Current Study Sponsor: Gilead Sciences
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Gilead Study Director; Gilead Sciences

• PRS Account: Gilead Sciences
• Verification Date: February 2024