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

Phase 3Active Not RecruitingNCT04994509

Gilead Sciences5,368 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

DOUBLE

Enrollment

5,368

Conditions

Pre-Exposure Prophylaxis of HIV Infection

Interventions

Oral Lenacapavir (LEN)DRUG

Tablets administered orally without regard to food

Subcutaneous (SC) Lenacapavir (LEN)DRUG

Administered via SC injections

F/TAFDRUG

Tablets administered orally

Eligibility

Sex: FEMALEMin age: 16 YearsMax age: 25 YearsHealthy volunteers:

Medical Language ↔ Plain English

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 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.

Locations (28)

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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

Data from ClinicalTrials.gov

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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

...and 18 more locations

Randomized Blinded Phase: HIV-1 Incidence Reported Per 100 PY for LEN, F/TAF and F/TDF

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.

Time frame: 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

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.

Time frame: 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

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).

Time frame: 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)

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.

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)

Randomized Blinded Phase: Percentage of Participants Experiencing Clinically Significant Laboratory Abnormalities

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.

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)