A Phase 2, Open-label, Multicenter, Randomized Study to Evaluate the Persistence, Safety, Acceptability, and Pharmacokinetics of Twice Yearly Long-acting Subcutaneous Lenacapavir for HIV Pre-Exposure Prophylaxis (PrEP) in People Who Would Benefit From PrEP
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 268
- 试验地点
- 28
- 主要终点
- Percentage of Participants with LEN and F/TDF Persistence through 52 Weeks
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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:
- •Condomless sex with ≥ 2 partners in the past 6 months
- •Diagnosis of a bacterial sexually transmitted infection (STI) in the past 12 months
- •Engagement in sex work or transactional sex in the past 12 months
- •Use of ≥ 2 courses of nonoccupational HIV post-exposure prophylaxis (nPEP) in the past 12 months
- •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)
排除标准
- •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/Exclusion criteria may apply
研究组 & 干预措施
Pharmacokinetic (PK) Tail Phase: F/TDF
After completion of the LEN OLE Phase or upon discontinuation from the Randomized Phase for those receiving LEN, participants will be transitioned to receive F/TDF in the PK Tail Phase. Participants will receive once daily F/TDF for 78 weeks, beginning 26 weeks after the last LEN injection
干预措施: Emtricitabine/tenofovir disoproxil fumarate (F/TDF) (Drug)
Randomized Phase: F/TDF
Participants will receive daily F/TDF (200/300 mg) fixed dose combination (FDC) tablets for up to 52 weeks.
干预措施: Emtricitabine/tenofovir disoproxil fumarate (F/TDF) (Drug)
LEN Open Label Extension (OLE) Phase
Participants in the F/TDF group will transition to get LEN and participants in the LEN group will continue to get LEN. All participants will get SC LEN on Day 1 and week 26 of the OLE phase.
干预措施: Lenacapavir Injection (Drug)
LEN Open Label Extension (OLE) Phase
Participants in the F/TDF group will transition to get LEN and participants in the LEN group will continue to get LEN. All participants will get SC LEN on Day 1 and week 26 of the OLE phase.
干预措施: Lenacapavir Tablet (Drug)
Randomized Phase: Lenacapavir (LEN) Group
Participants will receive subcutaneous (SC) LEN 927 mg on Day 1 and 26 weeks and oral LEN 600 mg on Day 1 and 2.
干预措施: Lenacapavir Injection (Drug)
Randomized Phase: Lenacapavir (LEN) Group
Participants will receive subcutaneous (SC) LEN 927 mg on Day 1 and 26 weeks and oral LEN 600 mg on Day 1 and 2.
干预措施: Lenacapavir Tablet (Drug)
结局指标
主要结局
Percentage of Participants with LEN and F/TDF Persistence through 52 Weeks
时间窗: 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.
次要结局
- 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)
- Pharmacokinetic (PK) Parameter: Ctrough for LEN at Week 26(Week 26)
- PK Parameter: Ctrough for LEN at Week 52(Week 52)