Phase 3, Multi-center, Double-blind, Randomized, Placebo-controlled Effectiveness and Safety Study to Assess the Role of Truvada® in Preventing HIV Acquisition in Women
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- FHI 360
- 入组人数
- 2,120
- 试验地点
- 4
- 主要终点
- HIV Infection
研究概览
简要总结
This Phase III, double-blind, randomized, placebo-controlled trial enrolled HIV-negative women from 4 sites in 3 countries (Kenya, Tanzania, South Africa). The study's purpose was to investigate the safety and effectiveness of a once-daily Truvada® pill (compared with placebo) in preventing HIV among HIV-uninfected women at risk of becoming infected through sexual intercourse.
The study population included HIV-antibody-negative women between the ages of 18-35 who were at risk of HIV acquisition through sexual intercourse. Each participant was randomized to take either a daily single oral tablet of Truvada®, which is a fixed-dose combination of emtricitabine (FTC; 200 mg) and tenofovir disoproxil fumarate (TDF; 300 mg), or an identical placebo.
After enrollment, each participant was followed every four weeks. All participants were followed for an additional eight weeks after study drug was stopped. Incidence rates of HIV infection were compared between the two groups (active drug and placebo) using the intent-to-treat principle.
详细描述
This Phase III, double-blind, randomized, placebo-controlled trial enrolled HIV-negative women from 4 sites in 3 countries (Kenya, Tanzania, South Africa). The study's purpose was to investigate the safety and effectiveness of a once-daily Truvada® pill (compared with placebo) in preventing HIV among HIV-uninfected women at risk of becoming infected through sexual intercourse.
The study population included HIV-antibody-negative women between the ages of 18-35 who were at risk of HIV acquisition through sexual intercourse. Each participant was randomized to take either a daily single oral tablet of Truvada®, which is a fixed-dose combination of emtricitabine (FTC; 200 mg) and tenofovir disoproxil fumarate (TDF; 300 mg), or an identical placebo. All participants received risk reduction counseling and condoms. Women had to be using a study-approved effective non-barrier contraceptive method at the time of enrollment and were asked to do so for the whole period they were on study drug. They received contraceptive counseling throughout the study. Any diagnosed, treatable sexually transmitted infection was treated free of charge.
After enrollment, each participant was followed every four weeks. All participants were followed for an additional eight weeks after study drug was stopped. Participants at risk for Hepatitis B Virus (HBV) flare were followed every four weeks for 12 weeks after stopping study product. Participants who acquired HIV infection during the study stopped taking the study drug at the time of HIV diagnosis, and will be followed for 52 weeks post diagnosis and were referred for care and treatment. Participants who became pregnant stopped taking the study drug but continued follow-up visits. Incidence rates of HIV infection were compared between the two groups (active drug and placebo) using the intent-to-treat principle.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 35 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Willing and able (see criterion 2) to provide written informed consent to be screened for and to participate in the trial
- •Able to answer a percentage of informed consent screening (75%) and enrollment (100%) comprehension quiz questions correctly
- •Between 18-35 years old, inclusive
- •At higher risk of becoming HIV infected
- •Have a final negative result according to the site-specific screening HIV testing algorithm and a final negative result at enrollment according to the study HIV testing algorithm
- •Willing to participate in all aspects of the study and to comply with study procedures, for up to 60 weeks, including:
- •Be randomized
- •Use study product as directed
- •Adhere to follow-up schedule and willing to be contacted by site staff between study visits (by phone and/or in person)
- •Use a study-approved effective non-barrier method of contraception for the duration of the study
- •Take study product, as evidenced by swallowing a vitamin tablet that is similar in size to the study product at enrollment
- •Provide contact information and agrees to some form of contact method throughout the study
- •Not intending to relocate out of the area for the duration of the study participation and does not have a job or other obligations that may require long absences from the area ( > 1 month at a time)
- •In general good health and have no condition (social or medical) which, in the opinion of the Site Investigator, would make study participation unsafe or complicate data interpretation
- •Not pregnant or breastfeeding, and does not anticipate a desire for pregnancy during the 52 weeks of on-product participation
- •Medically eligible at screening including:
- •Adequate renal function (serum creatinine ≤ upper limit of normal (ULN) of local range and creatinine clearance ≥ 60ml/min estimated by the Cockcroft-Gault Creatinine Clearance Formula
- •Adequate hepatic function (hepatic transaminases ALT and AST < 2x ULN [according to local normal ranges])
- •HBsAg negative
- •Serum phosphorus levels above the lower limit of the local normal range (according to local normal ranges - grade 3 & 4 hypophosphatemia will be excluded even if within normal local ranges)
- •Not received or receiving an experimental HIV vaccine, participating in another HIV prevention study or participating in any other clinical trial with a biomedical intervention
- •No clinical signs of liver disease (e.g., ascites, spider angiomata, hepatomegaly, jaundice)
- •No definite evidence of glycosuria or proteinuria (i.e., no repeated positive [ ≥ + 1 ] urine dipstick). If a urine dipstick is positive for either glucose and/or protein at the first test, a second urine sample will be tested.
- •No history of pathological bone fractures
- •No history of adverse reaction to latex
- •Not taking any of the following medications: nephrotoxic agents; aminoglycoside antibiotics (including gentamicin); intravenous (IV) amphotericin B; cidofovir; cisplatin; foscarnet; IV pentamidine; oral or IV vancomycin; oral or IV gancyclovir; other agents with significant nephrotoxic potential; drugs that slow renal excretion; probenecid; immune system modulators; systemic chemotherapeutic agents (i.e. cancer treatment medications); systemic corticosteroids; interleukin-2 (IL-2); immunomodulators; interferon (alpha, beta, or gamma); other antiretrovirals (including nucleoside analogs, non-nucleoside reverse transcriptase inhibitors, protease inhibitors or investigational antiretroviral agents)
排除标准
- 未提供
研究组 & 干预措施
Truvada Arm
Daily single oral tablet of Truvada (TDF/FTC), a fixed-dose combination of emtricitabine (FTC; 200 mg) and tenofovir disoproxil fumarate (TDF; 300 mg).
干预措施: Truvada (Drug)
Placebo Arm
Daily single oral tablet of Placebo. Tablets are identical to Truvada tablets in taste and appearance; however, they contain no active ingredients.
干预措施: Placebo (Other)
结局指标
主要结局
HIV Infection
时间窗: Cumulative HIV infection between enrollment and 52 weeks
HIV Seroconversion, with time to infection refined based on PCR results obtained from stored specimens.
Confirmed Grade 2 or Higher Serum Creatinine Toxicity
时间窗: cumulative toxicity through 52 weeks of product use and 4 weeks post product
Repeat specimens were collected to confirm chemistry toxicities. Grade 2 or higher serum creatinine toxicity was defined as ≥1.4 times the upper limit of normal
Frequency of Adverse Events (AEs) During and Within 4 Weeks After Study Product Administration
时间窗: 10-26 months per site
The total number of adverse events in the placebo and Truvada arms during and within 4 weeks after study product administration.
Confirmed Grade 3 or Higher AST Elevation
时间窗: Through 52 weeks on product and 4 weeks post-product
Grade 3 or higher AST elevation was defined as ≥ 2.6 times the upper limit of normal
Confirmed Grade 3 or Higher Reduction in Phosphorus
时间窗: Through 52 weeks on product and 4 weeks post-product
Repeat specimens were collected to confirm chemistry toxicities. Grade 3 phosphorus reduction was defined as ≤2.4mg/dL
Confirmed Grade 3 or Higher ALT Elevation
时间窗: Through 52 weeks on product and 4 weeks post-product
Grade 3 or higher ALT elevation was defined as ≥ 2.6 times the upper limit of normal
次要结局
- Pill Counts and Participant Report of Adherence to Once-daily Pill Taking(Up to 52 weeks)
- CD4+ T-cell Count(Up to 16 weeks)
- FTC and/or Tenofovir Resistance(up to 52 weeks)
- Pregnancy Complications(up to 60 weeks)
- Plasma HIV RNA Level (HIV-1 Viral Load)(up to 16 weeks)
- Participant Report of Change in Number of Sexual Partners(Up to 52 weeks)