Study of Lenacapavir and Emtricitabine/Tenofovir Disoproxil Fumarate (F/TDF) for Prevention of HIV in People Who Inject Drugs (HPTN 103)
- Conditions
- Pre-Exposure Prophylaxis of HIV Infection
- Interventions
- Drug: Emtricitabine/tenofovir disoproxil fumarate (F/TDF)
- Registration Number
- NCT06101342
- Lead Sponsor
- Gilead Sciences
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 180
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Open-label Extension Phase: LEN Lenacapavir Injection 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. Open-label Extension Phase: LEN Lenacapavir Tablet 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. Randomized Phase: Lenacapavir (LEN) Group Lenacapavir Injection Participants will receive subcutaneous (SC) LEN 927 mg on Day 1 and Week 26 and oral LEN 600 mg on Days 1 and 2. Randomized Phase: Lenacapavir (LEN) Group Lenacapavir Tablet Participants will receive subcutaneous (SC) LEN 927 mg on Day 1 and Week 26 and oral LEN 600 mg on Days 1 and 2. Randomized Phase: Emtricitabine/ Tenofovir Disoproxil Fumarate (F/TDF) Group Emtricitabine/tenofovir disoproxil fumarate (F/TDF) Participants will receive daily F/TDF (200/300 mg) fixed dose combination (FDC) tablets for up to 52 weeks. Pharmacokinetic (PK) Tail Phase: F/TDF Emtricitabine/tenofovir disoproxil fumarate (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.
- Primary Outcome Measures
Name Time Method 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
Name Time Method Satisfaction With Use of LEN and F/TDF as PrEP as Assessed by Percentage of Participants with Satisfaction Questionnaire Responses Up to Week 52 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.
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 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.
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 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.
Number of Participants with Adherence to LEN, as Assessed by On-time LEN Injections Received Up to Week 26
Trial Locations
- Locations (9)
UCLA Vine Street Clinic
🇺🇸Los Angeles, California, United States
UCSD AntiViral Research Center (AVRC)
🇺🇸San Diego, California, United States
University of Miami - Converge Miami Building
🇺🇸Miami, Florida, United States
Johns Hopkins Medicine Institute for Clinical and Translational Research, Clinical Research
🇺🇸Baltimore, Maryland, United States
Rutgers New Jersey Medical School, Department of Medicine
🇺🇸Newark, New Jersey, United States
ICAP at Columbia University- Bronx Prevention Center
🇺🇸Bronx, New York, United States
University of Pennsylvania, Division of Infectious Diseases Penn Prevention Research Unit
🇺🇸Philadelphia, Pennsylvania, United States
Houston AIDS Research Team CRS
🇺🇸Houston, Texas, United States
West Virginia University
🇺🇸Morgantown, West Virginia, United States