Study of Lenacapavir and Emtricitabine/Tenofovir Disoproxil Fumarate (F/TDF) for Prevention of HIV in People Who Inject Drugs (HPTN-103)

Study Overview
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Brief Summary
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The goals of this clinical study are to look at how lenacapavir (LEN) passes through the body and to assess the safety of LEN and emtricitabine/tenofovir disoproxil fumarate (coformulated; Truvada®) (F/TDF) for pre-exposure prophylaxis (PrEP) in people who inject drugs (PWID) in the United States (US). The primary objectives of this study are: To characterize the pharmacokinetics (PK) of LEN. To evaluate the safety of LEN and F/TDF for PrEP in US PWID.

Official Title
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A Phase 2, Open-Label, Multicenter, Randomized Study to Evaluate the Pharmacokinetics and Safety of Twice Yearly Long-Acting Subcutaneous Lenacapavir for Pre-Exposure Prophylaxis in People Who Inject Drugs

Conditions
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Pre-Exposure Prophylaxis of HIV Infection

Intervention / Treatment
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* Drug: Lenacapavir Injection
* Drug: Lenacapavir Tablet
* Drug: Emtricitabine/tenofovir disoproxil fumarate (F/TDF)


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Urine drug screen positive for any drug of misuse including, but not limited to, opioids (eg, fentanyl, heroin), stimulants (eg, cocaine, amphetamines), psychoactive drugs (eg, benzodiazepines), or a combination of these drugs. Evidence of recent injection (eg, track marks). Self-report of injection paraphernalia sharing in the prior 30 days. Hepatitis B virus (HBV) surface antigen (HBsAg) negative. Negative local rapid HIV-1/2 antibody (Ab)/antigen (Ag) test, central HIV-1/2 Ab/Ag, and HIV-1 RNA quantitative nucleic acid amplification testing (NAAT). Estimated glomerular filtration rate (GFR) at least 60 mL/min at screening according to the Cockcroft-Gault formula for creatinine clearance (CLcr). Key Exclusion Criteria: Self-reported history of previous positive results on an HIV test. Any reactive or positive HIV test result at screening or enrollment, even if HIV infection is not confirmed. Coenrollment in any other interventional research study or other concurrent studies that may interfere with this study (as provided by self-report or other available documentation) without prior approval from the Medical Monitor/Joint Clinical Management Committee while participating in this study. Past or current participation in HIV vaccine or HIV broadly neutralizing antibody study unless individual provides documentation of receipt of placebo (ie, not active product). Prior use of long-acting systemic pre-exposure prophylaxis (PrEP) (including cabotegravir (CAB) or islatravir studies). Acute viral hepatitis A or acute or chronic hepatitis B or C infection. Have a suspected or known active, serious infection(s) (eg, active tuberculosis, etc). Evidence of moderate or severe liver fibrosis or a history of or current clinical decompensated liver cirrhosis (eg, ascites, encephalopathy, variceal bleeding) Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Randomized Phase: Lenacapavir (LEN) Group<br>Participants will receive subcutaneous (SC) LEN 927 mg on Day 1 and Week 26 and oral LEN 600 mg on Days 1 and 2. | Drug: Lenacapavir Injection<br>* Administered subcutaneously<br>* Other names: GS-6207;Drug: Lenacapavir Tablet<br>* Administered orally<br>* Other names: GS-6207;|
| Experimental: Randomized Phase: Emtricitabine/ Tenofovir Disoproxil Fumarate (F/TDF) Group<br>Participants will receive daily F/TDF (200/300 mg) fixed dose combination (FDC) tablets for up to 52 weeks. | Drug: Emtricitabine/tenofovir disoproxil fumarate (F/TDF)<br>* Administered orally<br>* Other names: Truvada®;|
| Experimental: Pharmacokinetic (PK) Tail Phase: F/TDF<br>After the completion of the Randomized Phase, participants in LEN group will be transitioned to receive F/TDF FDC tablets and participants in F/TDF group will continue to receive F/TDF FDC tablets in the PK Tail Phase. All participants will receive F/TDF FDC tablets, once daily for up to 78 weeks beginning 26 weeks after the last LEN injection. | Drug: Emtricitabine/tenofovir disoproxil fumarate (F/TDF)<br>* Administered orally<br>* Other names: Truvada®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic (PK) Parameter: Ctrough for Lenacapavir (LEN): LEN Plasma concentration at the End of the Dosing Interval (Week 26) |  | Week 26 | 
| PK Parameter: Ctrough for LEN: LEN Plasma concentration at the End of the Dosing Interval (Week 52) |  | Week 52 | 
| Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) |  | First dose date up to 30 days post last dose at Week 78 | 
| Percentage of Participants Experiencing Treatment-emergent Clinical Laboratory Abnormalities with LEN and F/TDF |  | First dose date up to 30 days post last dose at Week 78 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| General Acceptability of LEN and F/TDF as PrEP as Assessed by Percentage of Participants with Acceptability Questionnaire Responses | To assess the acceptability of the study drug, the participants will complete questionnaire including a question on general acceptability of the assigned study drug on an ordinal 5-category scale with a response of: Completely unacceptable, Unacceptable, No opinion, Acceptable, or Completely acceptable. | Up to Week 52 | 
| Satisfaction With Use of LEN and F/TDF as PrEP as Assessed by Percentage of Participants with Satisfaction Questionnaire Responses | To assess the satisfaction with use of the study drug, the participants will complete questionnaire including a question on satisfaction with use of the assigned study drug on an ordinal 5-category scale with a response of: Very satisfied, Satisfied, Neutral, Dissatisfied, or Very dissatisfied. | Up to Week 52 | 
| Willingness to Use LEN and F/TDF as PrEP as Assessed by Percentage of Participants with Willingness to Use Questionnaire Responses | To assess the willingness to use the study drug, the participants will complete questionnaire including a question on willingness to use the assigned study drug on an ordinal 5-category scale with a response of: Definitely Yes, Probably yes, Not sure/undecided, Probably No, or Definitely No. | Up to Week 52 | 
| Number of Participants with Adherence to LEN, as Assessed by On-time LEN Injections Received |  | Up to Week 26 | 
| Number of Participants with Adherence to F/TDF as Assessed by Adherence Levels Based on Intracellular Tenofovir-diphosphate (TFV-DP) Concentrations in Dried Blood Spot (DBS) |  | Up to Week 78 |