A Phase III, Multi-Centre, Randomized Controlled Trial to Assess the Safety and Effectiveness of the Vaginal Microbicide 1% Tenofovir Gel in the Prevention of Human Immunodeficiency Virus Type 1 Infection in Women, and to Examine Effects of the Microbicide on the Incidence of Herpes Simplex Virus Type 2 Infection
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 2,059
- 试验地点
- 9
- 主要终点
- Safety
研究概览
简要总结
The purpose of the study is to assess the safety and effectiveness of intravaginal 1% tenofovir gel in preventing Human Immunodeficiency Virus (HIV-1) infection and Herpes Simplex Virus (HSV-2) infection in sexually active women.
详细描述
This is a phase III, multicenter trial to assess the safety and effectiveness of 1% tenofovir gel, administered vaginally by approximately 2900 sexually active women at high risk for sexually transmitted HIV. Approximately 2600 women aged 18-30 years old will be enrolled to achieve the required number of endpoints to show an effect on HIV-1 infection, while up to 300 additional women aged 31-40 years old will be enrolled to collect more safety information in this age group.
This is an event driven study that plans to randomize seronegative women. Participants will be randomized to a 1:1 ratio to receive 1% tenofovir gel or placebo gel. Each will be asked to insert a dose of the assigned study product within 12 hours prior to a coital event and another dose as soon as possible within 12 hours after a coital event. Participants will be advised to use only two doses of gel in a 24 hour period.
All women will be evaluated for the rates of adverse events and the rate of HIV seroconversion. In addition, the study will evaluate several secondary endpoints that bear directly on potential risks and benefits of vaginal tenofovir gel use.
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 40 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Confirmed age 18-40 years (inclusive)
- •Able and willing to provide written informed consent
- •Able and willing to provide adequate locator information for study retention and safety purposes
- •Sexually active, defined as having had vaginal intercourse at least twice in the past 30 days prior to screening
- •HIV negative on two rapid tests performed by study staff within 30 days of enrolment (see algorithm in Appendix 3).
- •No evidence of glycosuria
- •No evidence of proteinuria greater than trace*
- •No history of pathological bone fractures
- •Have a negative pregnancy test
- •Women currently breastfeeding may be enrolled in the study
- •Agree to use a study-approved effective non-barrier form of contraception
- •Agree to adhere to study visits and procedures
- •Willing to use study gel as advised
- •Not using or taking any of the following groups of medications:
- •Nephrotoxic agents
- •Drugs that slow renal excretion
- •Immune system modulators
- •Other antiretrovirals
排除标准
- •History of adverse reaction to latex.
- •Plans any of the following during the study period
- •To travel away from the study site for more than 30 consecutive days.
- •To relocate away from the study site.
- •To become pregnant.
- •To enrol in any other study of an investigational product or behaviour modification related to HIV prevention.
- •If in the opinion of the examining clinician, is not sexually active
- •Inadequate renal function (serum creatinine greater than 1.5mg/dl and creatinine clearance less than 50ml/min, as estimated using the method of Cockcroft and Gault96 )
- •Grade 3 and above ALT and AST at screening or any clinical sign of liver disease ( e.g. ascites, hepatomegaly, jaundice)
- •Abnormal serum phosphate levels (Grade 3 and above)
- •Has a clinically apparent finding on speculum pelvic examination (observed by study staff) involving deep epithelial disruption. Otherwise eligible participants with speculum pelvic examination findings involving deep epithelial disruption may proceed with enrolment after the findings have resolved and the inclusion/exclusion are met.
- •Received previously or receiving an experimental HIV vaccine
- •Currently participating in another HIV prevention intervention study or participation in any other clinical trial with a biomedical intervention in the last six months
- •Has current STI symptoms and/or other reproductive tract infection requiring treatment, as assessed by study staff. Otherwise eligible participants diagnosed during screening with infection(s) requiring treatment may be enrolled provided that treatment has been completed.
- •Any clinical evidence of untreated cervical abnormalities
- •Has any other condition that, based on the opinion of the Investigator or designee, would preclude provision of informed consent, make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives.
研究组 & 干预措施
Tenofovir 1% vaginal gel
Participants will be required to insert a single dose of assigned gel intravaginally up to 12 hours before coitus and a second dose within 12 hours after coitus but no more than 2 applications within a 24 hour period.
干预措施: Tenofovir gel (Drug)
Universal placebo gel
Participants will be required to insert a single dose of assigned gel intravaginally up to 12 hours before coitus and a second dose within 12 hours after coitus but no more than 2 applications within a 24 hour period.
干预措施: Universal placebo gel (Drug)
结局指标
主要结局
Safety
时间窗: 30 months
Grade 2, 3, and 4 clinical and laboratory adverse events as defined by the DAIDS toxicity table
Effectiveness
时间窗: 30 months
Incidence of HIV-1 infection: HIV incidence will be determine by detection of HIV antibodies using two HIV rapid tests (of which one will be FDA approved) according to algorithm in protocol. One of the rapid tests will detect both HIV-1 and HIV-2; the other will be specific for HIV-1. All endpoints will be reviewed by an expert committee (the Endpoint Adjudication Committee). In carrying out this review, the Committee will use guidelines prepared by the protocol committee for this purpose and recorded in the Manual of Procedures
次要结局
- Gel and condom use(30 months)
- HIV-1 incidence after product withdrawal(3 months after product withdrawal)
- Pregnancy(30 months)
- Incidence of HSV-2 infection(30 months)