A Phase 3, Randomized, Active-Controlled, Double-blind Clinical Study to Evaluate the Efficacy and Safety of Oral Islatravir Once-Monthly as Preexposure Prophylaxis in Cisgender Women at High Risk for HIV-1 Infection
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 730
- 试验地点
- 24
- 主要终点
- Number of Participants Who Discontinued Blinded Study Treatment Due to an AE
研究概览
简要总结
This study will evaluate whether oral islatravir (ISL) is effective in preventing Human Immunodeficiency Virus Type 1 (HIV-1) infection in women at high-risk for HIV-1 infection. The study will compare oral ISL taken once a month with standard-of-care medication for prevention of HIV-1 infection, emtricitabine/tenofovir disoproxil (FTC/TDF), taken once per day. The primary hypothesis is that oral ISL is more effective than FTC/TDF at reducing the incidence rate per year of confirmed HIV-1 infections.
详细描述
Based on laboratory findings of decreased lymphocyte and CD4+ T-cell counts across the islatravir program, dosing of blinded study intervention was halted on 13-Dec-2021 and screening and randomization of new participants was ended. Blinded assessments conducted prior to this date are designated as Study Part 1. During Study Part 2, participants from Part 1 have the option to receive daily open-label FTC/TDF while continuing in the study for safety monitoring. Study Part 3 was added to unblind each participant's Part 1 study intervention assignment, continue participants on FTC/TDF, and monitor safety.
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
- Triple (Participant, Care Provider, Investigator)
盲法说明
In Study Part 1, a double-blinding technique with in-house blinding will be used. ISL and FTC/TDF will be packaged identically relative to their matching placebos so that blind is maintained. The participant, the investigator, and Sponsor personnel or delegate(s) who are involved in the study intervention administration or clinical evaluation of the participants are unaware of the intervention assignments.
In Study Part 2, sponsor personnel not directly involved with blinded safety monitoring will be unblinded to participants' randomized study intervention in Part 1.
In Study Part 3, participants, investigators, and all Sponsor personnel will be unblinded to the participants' original randomized study intervention group.
入排标准
- 年龄范围
- 16 Years 至 45 Years（Child, Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Confirmed HIV-uninfected based on negative HIV-1/HIV-2 test results before randomization.
- •Sexually active (vaginal and/or anal sex) with a male sexual partner in the 30 days prior to screening.
- •High risk for HIV-1 infection.
- •Not pregnant or breastfeeding, and one of the following conditions applies: Not a woman of childbearing potential (WOCBP) or is a WOCBP and is using an acceptable contraceptive method during the intervention period and for at least 42 days after the last dose.
- •A WOCBP must have a negative pregnancy test within 24 hours prior to the first dose of study intervention.
排除标准
- •Hypersensitivity or other contraindication to any of the components of the study interventions as determined by the investigator.
- •Findings of chronic hepatitis B virus (HBV) infection or past HBV.
- •Current or chronic history of liver disease.
- •History of malignancy within 5 years of screening except for adequately-treated basal cell or squamous cell skin cancer, or in situ cervical cancer.
- •Past or current use of cabotegravir, lenacapavir, or any other long-acting HIV prevention product.
- •Currently participating in or has participated in an interventional clinical study with an investigational compound or device, within 30 days prior to Day
- •Expecting to conceive or donate eggs at any time during the study.
研究组 & 干预措施
ISL QM
ISL (islatravir) once monthly AND placebo to FTC/TDF (emtricitabine/tenofovir disoproxil) once daily. Following study-wide cessation of ISL administration, participants had the option to receive open-label FTC/TDF administered once daily.
干预措施: Islatravir (Drug)
ISL QM
ISL (islatravir) once monthly AND placebo to FTC/TDF (emtricitabine/tenofovir disoproxil) once daily. Following study-wide cessation of ISL administration, participants had the option to receive open-label FTC/TDF administered once daily.
干预措施: Placebo to FTC/TDF (Drug)
FTC/TDF QD
FTC/TDF (TRUVADA™ or generic product emtricitabine/tenofovir disoproxil) administered once daily. Placebo to ISL (islatravir) administered once monthly. Following study-wide cessation of ISL administration, participants had the option to continue on open-label FTC/TDF. Placebo was no longer administered once open label treatment began.
干预措施: FTC/TDF (Drug)
FTC/TDF QD
FTC/TDF (TRUVADA™ or generic product emtricitabine/tenofovir disoproxil) administered once daily. Placebo to ISL (islatravir) administered once monthly. Following study-wide cessation of ISL administration, participants had the option to continue on open-label FTC/TDF. Placebo was no longer administered once open label treatment began.
干预措施: Placebo to ISL (Drug)
结局指标
主要结局
Number of Participants Who Discontinued Blinded Study Treatment Due to an AE
时间窗: Up to 283 days
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinued blinded study treatment due to an AE will be reported for each treatment arm.
Incidence Rate Per Year of Confirmed HIV-1 Infection Among Participants During Blinded Treatment +42 Days Post-Blind
时间窗: Up to approximately 325 days
Incidence rate per year of confirmed HIV-1 infections is the number of participants with confirmed HIV-1 infections during the assessment period divided by the number of person-years in the arm. Data are based on participants with confirmed HIV-1 infection. The originally planned primary statistical analysis was removed via amendment when open-label treatment was initiated.
Number of Participants Who Experienced an Adverse Event (AE) During Blinded Treatment + 42 Days Post-Blind
时间窗: Up to approximately 325 days
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experienced an AE will be reported for each treatment arm.
次要结局
- Incidence Rate Per Year During Blinded Treatment of Confirmed HIV-1 Infection Among ISL-Treated Participants(Up to approximately 237 days)