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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Pre-Exposure Prophylaxis of HIV Infection

Intervention / Treatment
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* Drug: Oral Lenacapavir (LEN)
* Drug: Subcutaneous (SC) Lenacapavir (LEN)
* Drug: F/TAF
* Drug: F/TDF
* Drug: Placebo SC LEN
* Drug: PTM Oral LEN
* Drug: PTM F/TAF
* Drug: PTM F/TDF


Participation Criteria
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Eligibility Criteria
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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 pre-exposure prophylaxis (PrEP) Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 25 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Blinded Phase: LEN + Placebo-to-match (PTM) F/TAF<br>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 | Drug: Oral Lenacapavir (LEN)<br>* Tablets administered orally without regard to food<br>* Other names: GS-6207;Drug: Subcutaneous (SC) Lenacapavir (LEN)<br>* Administered via SC injections<br>* Other names: GS-6207;Drug: PTM F/TAF<br>* Tablets administered orally<br>|
| Experimental: Blinded Phase: LEN + PTM F/TDF<br>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 | Drug: Oral Lenacapavir (LEN)<br>* Tablets administered orally without regard to food<br>* Other names: GS-6207;Drug: Subcutaneous (SC) Lenacapavir (LEN)<br>* Administered via SC injections<br>* Other names: GS-6207;Drug: PTM F/TDF<br>* Tablets administered orally<br>|
| Experimental: Blinded Phase: Placebo LEN + F/TAF<br>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 | Drug: F/TAF<br>* Tablets administered orally<br>* Other names: Descovy®;Drug: Placebo SC LEN<br>* Administered via SC injections<br>Drug: PTM Oral LEN<br>* Tablets administered orally<br>|
| Experimental: Blinded Phase: Placebo LEN + F/TDF<br>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 | Drug: F/TDF<br>* Tablets administered orally<br>* Other names: Truvada®;Drug: Placebo SC LEN<br>* Administered via SC injections<br>Drug: PTM Oral LEN<br>* Tablets administered orally<br>|
| Experimental: LEN Open-Label Extension (OLE) Phase<br>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. | Drug: Oral Lenacapavir (LEN)<br>* Tablets administered orally without regard to food<br>* Other names: GS-6207;Drug: Subcutaneous (SC) Lenacapavir (LEN)<br>* Administered via SC injections<br>* Other names: GS-6207;|
| Experimental: Pharmacokinetic (PK) Tail Coverage Phase<br>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. | Drug: F/TDF<br>* Tablets administered orally<br>* Other names: Truvada®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) |