Pre-Exposure Prophylaxis of HIV Infection
Conditions
Brief summary
The goals of this clinical study are to learn more about the study drug lenacapavir (LEN), by comparing the consistent and continuous use of LEN and emtricitabine/tenofovir disoproxil fumarate (coformulated; Truvada®) (F/TDF), then by observing the safety of LEN and F/TDF, evaluating the acceptability of LEN injections and oral F/TDF, and observe how LEN moves throughout the body in people who would benefit from pre-exposure prophylaxis (PrEP). The primary objective of this study is to compare LEN and F/TDF consistent and continuous use among people who would benefit from PrEP.
Interventions
Administered subcutaneously
Administered orally
Administered orally
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Key Inclusion Criteria: * Able to comprehend and provide a signed written informed consent, which must be obtained prior to initiation of study procedures. * Cisgender men who have sex with men, transgender women, transgender men, cisgender women, and nonbinary people. * Increased likelihood of HIV acquisition as indicated by at least one of the following: 1. Condomless sex with ≥ 2 partners in the past 6 months 2. Diagnosis of a bacterial sexually transmitted infection (STI) in the past 12 months 3. Engagement in sex work or transactional sex in the past 12 months 4. Use of ≥ 2 courses of nonoccupational HIV post-exposure prophylaxis (nPEP) in the past 12 months 5. Condomless sex with a partner living with HIV who has unknown or unsuppressed viral load (≥ 200 copies/mL) in the past 12 months * 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) at screening. 1\) If rapid HIV-1/2 Ab/Ag tests are unavailable due to extenuating circumstances, sites may run a laboratory-instrumented HIV-1/2 Ab/Ag test at their local laboratory, only if they confirm this is a fourth-generation assay and the time from blood draw to injection at any injection visit is \< 48 hours. * Estimated glomerular filtration rate (GFR) at least 60 mL/min at screening according to the Cockcroft-Gault formula for creatinine clearance (CLcr): * (140 - age in years) × (weight in kg) x (0.85 if female) = CLcr (mL/min) / 72 × (serum creatinine in mg/dL) Key
Exclusion criteria
* Coenrollment in any other clinical study (including observational) without prior approval from the sponsor is prohibited while participating in this study. * Known hypersensitivity to the study drug, the metabolites, or formulation excipient. * Current use of PrEP, defined as the use of PrEP in the preceding 4 weeks. PrEP should not be discontinued to facilitate study participation. For cabotegravir, this is defined as 4 weeks since the next injection was due (ie, 12 weeks since their most recent cabotegravir injection). * Current use of nPEP, unless the prescribed course will be completed prior to randomization. * Past or current participation in HIV vaccine or HIV broadly neutralizing Ab study unless participant provides documentation of receipt of placebo (ie, not active product). * Acute viral hepatitis A, B, or C or evidence of chronic hepatitis B or C infection * Severe hepatic impairment or a history of or current clinical decompensated liver cirrhosis (eg, ascites, encephalopathy, variceal bleeding). * Have a suspected or known active, serious infection(s) (eg, active tuberculosis, etc). Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants with LEN and F/TDF Persistence through 52 Weeks | Up to Week 52 | This outcome measure will compare LEN and F/TDF persistence through 52 weeks, where persistence is defined by On-time LEN Injection at Day 1/Baseline and Week 26 and On-time Follow-up Visit at Week 52 for LEN arm and by Adherence Levels Based on tenofovir diphosphate (TFV-DP) concentrations in red blood cells consistent with ≥ 4 doses/week (≥ 700 fmol/punch) in dried blood spot (DBS) at Weeks 13, 26, 39, and 52 for F/TDF arm. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | First dose date up to 30 days post last dose at Week 78 | — |
| Overall acceptability of LEN and F/TDF as PrEP as Assessed by Percentage of Participants with responses to Question on Acceptability | Up to Week 52 | To assess the acceptability of the study drug, participants will complete the 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. |
| Pharmacokinetic (PK) Parameter: Ctrough for LEN at Week 26 | Week 26 | Ctrough is defined as the concentration at the end of the dosing interval. |
| PK Parameter: Ctrough for LEN at Week 52 | Week 52 | Ctrough is defined as the concentration at the end of the dosing interval. |
Countries
France, United Kingdom
Outcome results
None listed