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

Phase 3

Active, not recruiting

• Conditions: Pre-Exposure Prophylaxis of HIV Infection
• Interventions: Drug: Oral Lenacapavir (LEN); Drug: F/TAF; Drug: F/TDF; Drug: Subcutaneous (SC) Lenacapavir (LEN); Drug: Placebo SC LEN; Drug: PTM F/TDF; Drug: PTM F/TAF; Drug: PTM Oral LEN

• Registration Number: NCT04994509
• Lead Sponsor: Gilead Sciences

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 available

Study Timeline

• Study First Submitted: 2021-08-02
• Study First Submitted QC: 2021-08-02
• Study First Posted: 2021-08-06
• Study Start: 2021-08-30
• Primary Completion: 2024-05-08
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-21
• Last Update Posted: 2025-02-24
• Study Completion: 2027-07

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Female
• Target Recruitment: 5368

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Blinded Phase: LEN + PTM F/TDF	PTM F/TDF	Participants will receive the following for approximately 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
Blinded Phase: LEN + Placebo-to-match (PTM) F/TAF	Oral Lenacapavir (LEN)	Participants will receive the following for approximately 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
Blinded Phase: LEN + Placebo-to-match (PTM) F/TAF	Subcutaneous (SC) Lenacapavir (LEN)	Participants will receive the following for approximately 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
Blinded Phase: LEN + Placebo-to-match (PTM) F/TAF	PTM F/TAF	Participants will receive the following for approximately 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
Blinded Phase: LEN + PTM F/TDF	Oral Lenacapavir (LEN)	Participants will receive the following for approximately 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
Blinded Phase: LEN + PTM F/TDF	Subcutaneous (SC) Lenacapavir (LEN)	Participants will receive the following for approximately 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
Blinded Phase: Placebo LEN + F/TAF	Placebo SC LEN	Participants will receive the following for approximately 52 weeks: * SC placebo LEN every 26 weeks * Oral F/TAF 200/25 mg once daily * Oral PTM LEN on Days 1 and 2
Blinded Phase: Placebo LEN + F/TAF	PTM Oral LEN	Participants will receive the following for approximately 52 weeks: * SC placebo LEN every 26 weeks * Oral F/TAF 200/25 mg once daily * Oral PTM LEN on Days 1 and 2
Blinded Phase: Placebo LEN + F/TDF	Placebo SC LEN	Participants will receive the following for approximately 52 weeks: * SC placebo LEN every 26 weeks * Oral F/TDF 200/300 mg once daily * Oral PTM LEN on Days 1 and 2
Blinded Phase: Placebo LEN + F/TDF	PTM Oral LEN	Participants will receive the following for approximately 52 weeks: * SC placebo LEN every 26 weeks * Oral F/TDF 200/300 mg once daily * Oral PTM LEN on Days 1 and 2
LEN Open-Label Extension (OLE) Phase	Oral Lenacapavir (LEN)	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 until LEN becomes available or the sponsor elects to discontinue the study, whichever occurs first. Participants randomized to F/TAF or F/TDF will receive 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.
LEN Open-Label Extension (OLE) Phase	Subcutaneous (SC) Lenacapavir (LEN)	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 until LEN becomes available or the sponsor elects to discontinue the study, whichever occurs first. Participants randomized to F/TAF or F/TDF will receive 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.
Blinded Phase: Placebo LEN + F/TAF	F/TAF	Participants will receive the following for approximately 52 weeks: * SC placebo LEN every 26 weeks * Oral F/TAF 200/25 mg once daily * Oral PTM LEN on Days 1 and 2
Blinded Phase: Placebo LEN + F/TDF	F/TDF	Participants will receive the following for approximately 52 weeks: * SC placebo LEN every 26 weeks * Oral F/TDF 200/300 mg once daily * Oral PTM LEN on Days 1 and 2
Pharmacokinetic (PK) Tail Coverage Phase	F/TDF	Participants who prematurely discontinue study drug in the randomized blinded phase will transition into the PK Tail Coverage phase. Participants will receive oral F/TDF once daily for 78 weeks beginning 26 weeks after the last LEN injection.

Primary Outcome Measures

Name	Time	Method
Incidence Phase: Background HIV Incidence Reported Per 100-Person-Years (PY)	At Screening
Randomized Phase: HIV Incidence Reported Per 100-PY of Follow-up	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 Outcome Measures

Name	Time	Method
HIV Incidence Among Participants While Adherent to Study Drug	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	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	When all participants have a minimum of 52 weeks of exposure to study drug or permanent discontinuation, whichever occurs first (maximum approximately 3 years)

Trial Locations

Locations (28)

Emavundleni Research Centre; 🇿🇦 Cape Town, South Africa

The Aurum Institute: Rustenburg Clinical Research Centre; 🇿🇦 Rustenburg, South Africa

Synergy Biomed Research Institute (SBRI); 🇿🇦 East London, South Africa

Perinatal HIV Research Unit (PHRU) Soweto Kliptown; 🇿🇦 Kliptown, South Africa

CAPRISA eThekwini Clinical Research Site; 🇿🇦 Durban, South Africa

CAPRISA Vulindlela Clinical Research Site; 🇿🇦 Durban, South Africa

Setshaba Research Centre; 🇿🇦 Gauteng, South Africa

Madibeng Centre for Research; 🇿🇦 Brits, South Africa

The Aurum Institute: Pretoria Clinical Research Centre; 🇿🇦 Pretoria, South Africa

FPD-DTHF Ndevana Community Research Site; 🇿🇦 Vincent, South Africa

Qhakaza Mbokodo Research Clinic; 🇿🇦 Ladysmith, South Africa

Desmond Tutu Health Foundation Clinical Trials Unit; 🇿🇦 Cape Town, South Africa

Botha's Hill Clinical Research Site, HIV Prevention Research Unit; 🇿🇦 Durban, South Africa

Phoenix Clinical Research Site, South African Medical Research Council, HIV and Other Infectious Disease Research Unit; 🇿🇦 Kwa Zulu Natal, South Africa

Africa Health Research Institute; 🇿🇦 Mtubatuba, South Africa

Makerere-Kalangala Clinical Research site; 🇺🇬 Kalangala, Uganda

AMBSO Masaka Clinical Research site; 🇺🇬 Kyotera- Masaka Region, Uganda

Makerere University- John Hopkins University (MU-JHU) Mityana Research Site (MU-JHU) Care Ltd; 🇺🇬 Mityana Town, Uganda

Verulam Clinical Research Site, South African Medical Research Council, HIV and Other Infectious Disease Research Unit; 🇿🇦 Kwa Zulu Natal, South Africa

Tongaat Clinical Research Site, South African Medical Research Council, HIV and Other Infectious Disease Research Unit; 🇿🇦 Kwa Zulu Natal, South Africa

Vuka Research Clinic; 🇿🇦 Cape Town, South Africa

MatCH Research Unit, Suite 1112, 11th Floor; 🇿🇦 Durban, South Africa

Wits Reproductive Health & HIV Institute (Wits RHI); 🇿🇦 Johannesburg, South Africa

The Aurum Institute: Gavin J Churchyard Legacy Centre, Klerksdorp Clinical Research Centre; 🇿🇦 Klerksdorp, South Africa

Chatsworth Clinical Research Site, South African Medical Research Council, HIV and Other Infectious Disease Research Unit; 🇿🇦 Kwa Zulu Natal, South Africa

The Aurum Institute: Tembisa Clinical Research Centre; 🇿🇦 Tembisa, South Africa

Desmond Tutu Health Foundation - Masiphumelele Research Office; 🇿🇦 Sunnydale, South Africa

CAPRISA Umlazi Clinical Research Site; 🇿🇦 Umlazi, South Africa