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
Trial Snapshot
- Phase
- Phase 2
- Status
- Active, not recruiting
- Sponsor
- Gilead Sciences
- Enrollment
- 181
- Locations
- 17
- Primary Endpoint
- Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
Study Overview
Brief Summary
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 (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 and to evaluate the safety of LEN and F/TDF for PrEP in US PWID.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
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).
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). In individuals with active hepatitis C, Fibrosis-4 (FIB-4) score > 3.25 (formula provided below).
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Arms & Interventions
Randomized Phase: Lenacapavir (LEN) Group
Participants will receive subcutaneous (SC) LEN 927 mg on Day 1 and Week 26 and oral LEN 600 mg on Days 1 and 2.
Intervention: Lenacapavir Injection (Drug)
Randomized Phase: Emtricitabine/ Tenofovir Disoproxil Fumarate (F/TDF) Group
Participants will receive daily F/TDF (200/300 mg) fixed dose combination (FDC) tablets for up to 52 weeks.
Intervention: Emtricitabine/tenofovir disoproxil fumarate (F/TDF) (Drug)
Pharmacokinetic (PK) Tail Phase: F/TDF
Participants eligible for the PK Tail Phase will receive open-label oral F/TDF once daily for up to 78 weeks and complete study visits every 13 weeks (± 7 days). PK Tail Day 1 visit will occur 26 weeks (± 7 days) after the last SC LEN injection.
Intervention: Emtricitabine/tenofovir disoproxil fumarate (F/TDF) (Drug)
Randomized Phase: Lenacapavir (LEN) Group
Participants will receive subcutaneous (SC) LEN 927 mg on Day 1 and Week 26 and oral LEN 600 mg on Days 1 and 2.
Intervention: Lenacapavir Tablet (Drug)
Open-label Extension Phase: LEN
Participants randomized to LEN in the Randomized Phase who choose to participate in the LEN Open-Label Extension (OLE) Phase will receive SC LEN every 26 weeks (± 7 days) and have study visits every 13 weeks (± 7 days). Participants randomized to F/TDF in the Randomized Phase who choose to participate in LEN OLE Phase will switch to SC LEN and have study visits at LEN OLE Day 1, Week 4 (± 2 days), Week 13 (± 7 days), and every 13 weeks (± 7 days) thereafter. SC LEN will be administered at the LEN OLE Day 1 visit and every 26 weeks thereafter. These participants will also receive loading doses of oral LEN on OLE Days 1 and 2. Upon completion of the LEN OLE Phase, participants will transition to local HIV prevention services and return for a 30-day follow-up visit. At that time, participation in the study will end.
Intervention: Lenacapavir Tablet (Drug)
Open-label Extension Phase: LEN
Participants randomized to LEN in the Randomized Phase who choose to participate in the LEN Open-Label Extension (OLE) Phase will receive SC LEN every 26 weeks (± 7 days) and have study visits every 13 weeks (± 7 days). Participants randomized to F/TDF in the Randomized Phase who choose to participate in LEN OLE Phase will switch to SC LEN and have study visits at LEN OLE Day 1, Week 4 (± 2 days), Week 13 (± 7 days), and every 13 weeks (± 7 days) thereafter. SC LEN will be administered at the LEN OLE Day 1 visit and every 26 weeks thereafter. These participants will also receive loading doses of oral LEN on OLE Days 1 and 2. Upon completion of the LEN OLE Phase, participants will transition to local HIV prevention services and return for a 30-day follow-up visit. At that time, participation in the study will end.
Intervention: Lenacapavir Injection (Drug)
Outcomes
Primary Outcomes
Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
Time Frame: First dose date up to 30 days post last dose at Week 52
Percentage of Participants Experiencing Treatment-emergent Clinical Laboratory Abnormalities with LEN and F/TDF
Time Frame: First dose date up to 30 days post last dose at Week 52
Pharmacokinetic (PK) Parameter: Ctrough for Lenacapavir (LEN): LEN Plasma concentration at the End of the Dosing Interval (Week 26)
Time Frame: Week 26
PK Parameter: Ctrough for LEN: LEN Plasma concentration at the End of the Dosing Interval (Week 52)
Time Frame: Week 52
Secondary Outcomes
- Number of Participants with Adherence to LEN, as Assessed by On-time LEN Injections Received(Up to Week 26)
- Satisfaction With Use of LEN and F/TDF as PrEP as Assessed by Percentage of Participants with Satisfaction Questionnaire Responses(Up to Week 52)
- 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)
- General Acceptability of LEN and F/TDF as PrEP as Assessed by Percentage of Participants with Acceptability Questionnaire Responses(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(Up to Week 52)