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

NCT04994509 | Active Not Recruiting Phase 3 Results DMC FDA Drug

• 2 other identifiers: GS-US-412-5624DOH-27- 072021-6125
• Study Type: interventional
• Target: 5,368
• Locations: 2 countries
• Sites: 28

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.

Conditions

Pre-Exposure Prophylaxis of HIV Infection

Outcome Measures

Primary Outcomes (2)

• Incidence Phase: Recent Infection Testing Algorithm (RITA) Estimate of the Background Human Immunodeficiency-1 Virus Infection Incidence Rate (bHIV) Per 100 Person Years (PY)

  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.

  Incidence Phase Screening Visit (Day 1)

• Randomized Blinded Phase: HIV-1 Incidence Reported Per 100 PY for LEN and F/TAF Compared to Participants in All Screened Set

  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.

  When at least 50% of the participants completed 52 weeks of follow-up after randomization or permanently discontinued from the study (maximum 143 weeks)

Secondary Outcomes (5)

• 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)

• 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)

• 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)

• 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)

• 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)

Study Arms (5)

Randomized Blinded Phase: Lenacapavir

EXPERIMENTAL

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.

Drug: Oral Lenacapavir (LEN); Drug: Subcutaneous (SC) Lenacapavir (LEN); Drug: PTM F/TAF; Drug: PTM F/TDF

Randomized Blinded Phase: F/TAF

EXPERIMENTAL

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.

Drug: F/TAF; Drug: Placebo SC LEN; Drug: PTM Oral LEN

Randomized Blinded Phase: F/TDF

EXPERIMENTAL

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.

Drug: F/TDF; Drug: Placebo SC LEN; Drug: PTM Oral LEN

LEN Open-Label Extension (OLE) Phase

EXPERIMENTAL

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.

Drug: Oral Lenacapavir (LEN); Drug: Subcutaneous (SC) Lenacapavir (LEN)

Pharmacokinetic (PK) Tail Coverage Phase

EXPERIMENTAL

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.

Drug: F/TDF

Interventions

Oral Lenacapavir (LEN) DRUG

Tablets administered orally without regard to food

Also known as: GS-6207

LEN Open-Label Extension (OLE) Phase; Randomized Blinded Phase: Lenacapavir

F/TAF DRUG

Tablets administered orally

Also known as: Descovy®

Randomized Blinded Phase: F/TAF

Subcutaneous (SC) Lenacapavir (LEN) DRUG

Administered via SC injections

Also known as: GS-6207, Yeztugo®, Yeytuo®

LEN Open-Label Extension (OLE) Phase; Randomized Blinded Phase: Lenacapavir

F/TDF DRUG

Tablets administered orally

Also known as: Truvada®

Pharmacokinetic (PK) Tail Coverage Phase; Randomized Blinded Phase: F/TDF

Placebo SC LEN DRUG

Administered via SC injections

Randomized Blinded Phase: F/TAF; Randomized Blinded Phase: F/TDF

PTM Oral LEN DRUG

Tablets administered orally

Randomized Blinded Phase: F/TAF; Randomized Blinded Phase: F/TDF

PTM F/TAF DRUG

Tablets administered orally

Randomized Blinded Phase: Lenacapavir

PTM F/TDF DRUG

Tablets administered orally

Randomized Blinded Phase: Lenacapavir

Eligibility Criteria

• Age: 16 Years - 25 Years
• Gender Eligibility Details: Cisgender Female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (28)

Madibeng Centre for Research

Brits, 2500, South Africa

Location

Emavundleni Research Centre

Cape Town, 7750, South Africa

Location

Vuka Research Clinic

Cape Town, 7784, South Africa

Location

Desmond Tutu Health Foundation Clinical Trials Unit

Cape Town, 7925, South Africa

Location

Botha's Hill Clinical Research Site, HIV Prevention Research Unit

Durban, 3660, South Africa

Location

CAPRISA eThekwini Clinical Research Site

Durban, 4001, South Africa

Location

CAPRISA Vulindlela Clinical Research Site

Durban, 4001, South Africa

Location

MatCH Research Unit, Suite 1112, 11th Floor

Durban, 4001, South Africa

Location

Synergy Biomed Research Institute (SBRI)

East London, South Africa

Location

Setshaba Research Centre

Gauteng, 152, South Africa

Location

Wits Reproductive Health & HIV Institute (Wits RHI)

Johannesburg, 2038, South Africa

Location

The Aurum Institute: Gavin J Churchyard Legacy Centre, Klerksdorp Clinical Research Centre

Klerksdorp, 2571, South Africa

Location

Perinatal HIV Research Unit (PHRU) Soweto Kliptown

Kliptown, 1809, South Africa

Location

Phoenix Clinical Research Site, South African Medical Research Council, HIV and Other Infectious Disease Research Unit

Kwa Zulu Natal, 4061, South Africa

Location

Verulam Clinical Research Site, South African Medical Research Council, HIV and Other Infectious Disease Research Unit

Kwa Zulu Natal, 4340, South Africa

Location

Tongaat Clinical Research Site, South African Medical Research Council, HIV and Other Infectious Disease Research Unit

Kwa Zulu Natal, 4400, South Africa

Location

Chatsworth Clinical Research Site, South African Medical Research Council, HIV and Other Infectious Disease Research Unit

Kwa Zulu Natal, South Africa

Location

Qhakaza Mbokodo Research Clinic

Ladysmith, 3370, South Africa

Location

Africa Health Research Institute

Mtubatuba, 3935, South Africa

Location

The Aurum Institute: Pretoria Clinical Research Centre

Pretoria, 0087, South Africa

Location

The Aurum Institute: Rustenburg Clinical Research Centre

Rustenburg, 299, South Africa

Location

Desmond Tutu Health Foundation - Masiphumelele Research Office

Sunnydale, 7705, South Africa

Location

The Aurum Institute: Tembisa Clinical Research Centre

Tembisa, 1632, South Africa

Location

CAPRISA Umlazi Clinical Research Site

Umlazi, 4066, South Africa

Location

FPD-DTHF Ndevana Community Research Site

Vincent, 5217, South Africa

Location

Makerere-Kalangala Clinical Research site

Kalangala, Uganda

Location

AMBSO Masaka Clinical Research site

Kyotera- Masaka Region, Uganda

Location

Makerere University- John Hopkins University (MU-JHU) Mityana Research Site (MU-JHU) Care Ltd

Mityana Town, Uganda

Location

Related Publications (1)

• Bekker LG, Das M, Abdool Karim Q, Ahmed K, Batting J, Brumskine W, Gill K, Harkoo I, Jaggernath M, Kigozi G, Kiwanuka N, Kotze P, Lebina L, Louw CE, Malahleha M, Manentsa M, Mansoor LE, Moodley D, Naicker V, Naidoo L, Naidoo M, Nair G, Ndlovu N, Palanee-Phillips T, Panchia R, Pillay S, Potloane D, Selepe P, Singh N, Singh Y, Spooner E, Ward AM, Zwane Z, Ebrahimi R, Zhao Y, Kintu A, Deaton C, Carter CC, Baeten JM, Matovu Kiweewa F; PURPOSE 1 Study Team. Twice-Yearly Lenacapavir or Daily F/TAF for HIV Prevention in Cisgender Women. N Engl J Med. 2024 Oct 3;391(13):1179-1192. doi: 10.1056/NEJMoa2407001. Epub 2024 Jul 24.

  PMID: 39046157 BACKGROUND

Related Links

• Gilead Clinical Trials Website

MeSH Terms

Interventions

lenacapavir; Injections, Subcutaneous; emtricitabine tenofovir alafenamide; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

Intervention Hierarchy (Ancestors)

Injections; Drug Administration Routes; Drug Therapy; Therapeutics; Tenofovir; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Emtricitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations

Limitations and Caveats

Due to data monitoring committee recommendation to stop the study early if the prespecified evaluation criteria were met, this is the date by when at least 50% of the participants were followed up for at least 52 weeks in the study.

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 2, 2021
• First Posted: August 6, 2021
• Study Start: August 30, 2021
• Primary Completion: May 27, 2024
• Study Completion (Estimated): January 1, 2028
• Last Updated: March 30, 2026
• Results First Posted: June 19, 2025

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

UG (3); ZA (25)