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/TAF; Drug: PTM Oral LEN; Drug: PTM F/TDF

• Registration Number: NCT04994509
• Lead Sponsor: Gilead Sciences

Brief Summary

The goal of this study is to evaluate the efficacy of the study drugs, lenacapavir (LEN) and emtricitabine/tenofovir alafenamide (F/TAF) in preventing HIV infection, in adolescent girls and young women (AGYW).

The primary objective of this study is to evaluate the efficacy of LEN and F/TAF for HIV-1 PrEP in AGYW at risk of HIV-1 infection.

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: 2024-05-27
• Results First Submitted: 2025-05-20
• Status Verified: 2025-06
• Results First Submitted QC: 2025-06-17
• Results First Posted: 2025-06-19
• Last Update Submitted: 2025-06-27
• Last Update Posted: 2025-07-17
• Study Completion: 2028-01-01

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 any long-acting systemic HIV pre-exposure prophylaxis (PrEP) or prior HIV postexposure prophylaxis (PEP) in the past 12 weeks.

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Randomized Blinded Phase: Lenacapavir	Oral Lenacapavir (LEN)	Participants will receive lenacapavir (LEN) 927 mg injection, every 26 weeks starting on Day 1 for up to approximately 52 weeks. Participants will also receive loading dose of LEN 600 mg, tablet, once daily on Day 1 and Day 2. Participants will receive placebo to match (PTM) emtricitabine/tenofovir disoproxil fumarate (F/TDF) or PTM emtricitabine/tenofovir alafenamide (F/TAF), once daily, up to approximately 52 weeks.
Randomized Blinded Phase: Lenacapavir	Subcutaneous (SC) Lenacapavir (LEN)	Participants will receive lenacapavir (LEN) 927 mg injection, every 26 weeks starting on Day 1 for up to approximately 52 weeks. Participants will also receive loading dose of LEN 600 mg, tablet, once daily on Day 1 and Day 2. Participants will receive placebo to match (PTM) emtricitabine/tenofovir disoproxil fumarate (F/TDF) or PTM emtricitabine/tenofovir alafenamide (F/TAF), once daily, up to approximately 52 weeks.
Randomized Blinded Phase: Lenacapavir	PTM F/TAF	Participants will receive lenacapavir (LEN) 927 mg injection, every 26 weeks starting on Day 1 for up to approximately 52 weeks. Participants will also receive loading dose of LEN 600 mg, tablet, once daily on Day 1 and Day 2. Participants will receive placebo to match (PTM) emtricitabine/tenofovir disoproxil fumarate (F/TDF) or PTM emtricitabine/tenofovir alafenamide (F/TAF), once daily, up to approximately 52 weeks.
Randomized Blinded Phase: Lenacapavir	PTM F/TDF	Participants will receive lenacapavir (LEN) 927 mg injection, every 26 weeks starting on Day 1 for up to approximately 52 weeks. Participants will also receive loading dose of LEN 600 mg, tablet, once daily on Day 1 and Day 2. Participants will receive placebo to match (PTM) emtricitabine/tenofovir disoproxil fumarate (F/TDF) or PTM emtricitabine/tenofovir alafenamide (F/TAF), once daily, up to approximately 52 weeks.
Randomized Blinded Phase: F/TAF	F/TAF	Participants will receive F/TAF, once daily up to approximately 52 weeks. Participants will also receive PTM LEN injection, every 26 weeks, starting on Day 1 up to approximately 52 weeks. Participants will receive PTM LEN tablet, once daily on Day 1 and Day 2.
Randomized Blinded Phase: F/TAF	Placebo SC LEN	Participants will receive F/TAF, once daily up to approximately 52 weeks. Participants will also receive PTM LEN injection, every 26 weeks, starting on Day 1 up to approximately 52 weeks. Participants will receive PTM LEN tablet, once daily on Day 1 and Day 2.
Randomized Blinded Phase: F/TAF	PTM Oral LEN	Participants will receive F/TAF, once daily up to approximately 52 weeks. Participants will also receive PTM LEN injection, every 26 weeks, starting on Day 1 up to approximately 52 weeks. Participants will receive PTM LEN tablet, once daily on Day 1 and Day 2.
Randomized Blinded Phase: F/TDF	F/TDF	Participants will receive F/TDF, once daily up to approximately 52 weeks. Participants will also receive PTM LEN injection, every 26 weeks starting on Day 1 up to approximately 52 weeks. Participants will receive PTM LEN tablet, once daily on Day 1 and Day 2.
Randomized Blinded Phase: F/TDF	Placebo SC LEN	Participants will receive F/TDF, once daily up to approximately 52 weeks. Participants will also receive PTM LEN injection, every 26 weeks starting on Day 1 up to approximately 52 weeks. Participants will receive PTM LEN tablet, once daily on Day 1 and Day 2.
Randomized Blinded Phase: F/TDF	PTM Oral LEN	Participants will receive F/TDF, once daily up to approximately 52 weeks. Participants will also receive PTM LEN injection, every 26 weeks starting on Day 1 up to approximately 52 weeks. Participants will receive PTM LEN tablet, once daily on Day 1 and Day 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 LEN 927 mg injection, 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 LEN 927 mg injection on OLE Day 1, Week 26, and every 26 weeks thereafter. Participants will also receive LEN 600 mg tablet 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 LEN 927 mg injection, 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 LEN 927 mg injection on OLE Day 1, Week 26, and every 26 weeks thereafter. Participants will also receive LEN 600 mg tablet on OLE 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 F/TDF, once daily, for 78 weeks beginning 26 weeks after the last LEN injection.

Primary Outcome Measures

Name	Time	Method
Incidence Phase: Recent Infection Testing Algorithm (RITA) Estimate of the Background Human Immunodeficiency-1 Virus Infection Incidence Rate (bHIV) Per 100 Person Years (PY)	Incidence Phase Screening Visit (Day 1)	bHIV per 100 PY in the Incidence Phase was calculated using RITA.; The RITA incorporated HIV-1 testing results and recency assay testing results to estimate the bHIV. Recency assay testing was performed for participants in the All Screened Set found to have HIV-1 infection at the Incidence Phase Screening Visit as defined below. Participants were considered to have recent HIV-1 infection if the normalized optical density (ODn) was below 1.5 threshold using the Sedia limiting antigen avidity enzyme immunoassay (LAg-EIA) and the HIV-1 RNA (viral load) was \> 75 copies/mL of blood.; HIV-1 infection was defined as participants having at least one of the following central lab results at the Incidence Phase screening visit: * Positive HIV-1/2 differentiation Ab, OR; * Positive HIV-1 ribonucleic acid (RNA) qualitative test, OR; * HIV-1 RNA quantitative test ≥200 copies/mL.
Randomized Blinded Phase: HIV-1 Incidence Reported Per 100 PY for LEN and F/TAF Compared to Participants in All Screened Set	When at least 50% of the participants completed 52 weeks of follow-up after randomization or permanently discontinued from the study (maximum 143 weeks)	HIV-1 incidence per 100 PY for LEN and F/TAF was calculated as the number of participants who acquired HIV-1 divided by the total of a) for participants not diagnosed with HIV-1, sum of all duration of follow-up time in years, while at risk of HIV-1 infection (where a year is 365.25 days) and b) for participants diagnosed with HIV-1, sum of all duration of follow-up time up to confirmed HIV-1 diagnoses.; HIV-1 diagnosis was determined by an HIV adjudication committee who reviewed potential HIV-1 infection events in the randomized participants. The committee, in a blinded, consistent, and unbiased manner, determined whether HIV test results confirmed HIV-1 infection and determined the date of diagnosis for each case, defined as the date of the earliest study visit with evidence of HIV infection considering both prospective HIV testing and back-testing of archived samples.; bHIV incidence per 100 PY in All Screened Set was estimated as described in outcome measure#1.

Secondary Outcome Measures

Name	Time	Method
Randomized Blinded Phase: HIV-1 Incidence Reported Per 100 PY for LEN, F/TAF and F/TDF	When at least 50% of the participants completed 52 weeks of follow-up after randomization or permanently discontinued from the study (maximum 143 weeks)	HIV-1 incidence per 100 PY was calculated as the number of participants who acquired HIV-1 divided by the total of a) for participants not diagnosed with HIV-1, sum of all duration of follow-up time in years, while at risk of HIV-1 infection (where a year is 365.25 days) and b) for participants diagnosed with HIV-1, sum of all duration of follow-up time up to confirmed HIV-1 diagnoses.; HIV-1 diagnosis was determined by an HIV adjudication committee who reviewed potential HIV-1 infection events in the randomized participants. The committee, in a blinded, consistent, and unbiased manner, determined whether HIV test results confirmed HIV-1 infection and determined the date of diagnosis for each case, defined as the date of the earliest study visit with evidence of HIV infection considering both prospective HIV testing and back-testing of archived samples.
Randomized Blinded Phase: HIV-1 Incidence Among Participants Adherent to LEN	When at least 50% of the participants completed 52 weeks of follow-up after randomization or permanently discontinued from the study (maximum 143 weeks)	A participant was defined as adherent to LEN if they have received all per-protocol administrations of LEN within 28 weeks since the previous administration. The incidence of HIV-1 infection per 100 PY calculation is defined in outcome measure #2.
Randomized Blinded Phase: Percentage of Participants Adherent to F/TAF in HIV-1 Diagnosed Participants and Their Matched Controls	When at least 50% of the participants completed 52 weeks of follow-up after randomization or permanently discontinued from the study (maximum 143 weeks)	A participant's adherence to F/TAF was measured by tenofovir diphosphate (TFV-DP) in dried blood spot (DBS) samples, where \<450 fmol/punch associates with an adherence of \<2 days per week. The data is reported in two categories: low adherence (\<2 days per week) and not low adherence (\>= 2 days per week).
Randomized Blinded Phase: Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)	When all participants have a minimum of 52 weeks of exposure to study drug or permanent discontinuation, whichever occurs first (maximum approximately 3 years)	TEAEs are defined as 1 or both of the following: * Any adverse events (AEs) leading to premature discontinuation of study drug, or; * Any AEs with an onset date on or after the study drug start date and no later than the last exposure date after permanent discontinuation of the study drug.; An AE was any untoward medical occurrence in a clinical study participant administered a study drug that did not necessarily had a causal relationship with the treatment.
Randomized Blinded Phase: 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)	Treatment-emergent laboratory abnormalities were defined as values that increased at least 1 toxicity grade from baseline at any post-baseline visit, up to and including the last exposure date for participants who permanently discontinued study drug, or the last available date in the database snapshot for participants who were still on treatment at the time of an analysis.

Trial Locations

Locations (28)

Madibeng Centre for Research; 🇿🇦 Brits, South Africa

Emavundleni Research Centre; 🇿🇦 Cape Town, South Africa

Vuka Research Clinic; 🇿🇦 Cape Town, 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

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

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

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

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

Setshaba Research Centre; 🇿🇦 Gauteng, South Africa

Scroll for more (18 remaining)