A DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED PHASE I/II TRIAL TO EVALUATE THE SAFETY OF DAPIVIRINE GEL 4759, 0.05% 2.5g AND DAPIVIRINE GEL 4789, 0.05% 2.5g FORMULATIONS AS COMPARED TO THE VAGINAL HEC-BASED UNIVERSAL PLACEBO GEL, 2.5g IN HEALTHY HIV-NEGATIVE WOMEN
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 128
- 试验地点
- 5
- 主要终点
- The Percentage of Women With the Composite Endpoint of Abnormal Safety Findings.
研究概览
简要总结
A double-blind, randomized, placebo-controlled Phase I/II trial to evaluate the safety of dapivirine Gel 4759, 0.05% 2.5 g and dapivirine Gel 4789, 0.05% 2.5 g formulations as compared to the vaginal HEC-based Universal placebo gel, 2.5 g in healthy HIV-negative women
详细描述
This was a double-blind, randomized, placebo-controlled trial, to be conducted over 10 months at five research centers in the USA among 180 healthy, sexually active women, to assess the safety and acceptability of dapivirine Gel 4759, 0.05% 2.5 g, and dapivirine Gel 4789, 0.05% 2.5 g, both vaginal microbicides containing dapivirine, compared to the vaginal HEC-based Universal placebo gel, 2.5 g, containing no active ingredient, used once daily for a period of 12 weeks.
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
- Double (Participant, Investigator)
盲法说明
Potential participants who provide inform consent will be invited to screen for the trial. All participants who consent to participate in the trial and meet specified inclusion/exclusion criteria will be invited to enrol. At enrolment women will be randomly assigned in a 1:1:1 ratio to one of three groups.
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
- •Women 18 to 40 years of age inclusive who can give written informed consent
- •Available for all visits and consent to follow all procedures scheduled for the trial
- •Healthy and self-reported sexually active
- •HIV-negative as determined by an HIV test at time of enrollment
- •Willing to be on a stable form of contraception
- •In the absence of the use of exogenous hormone(s), have a self-reported regular menstrual cycle
- •Upon pelvic/speculum examination and colposcopy at the enrollment visit, the cervix and vagina appear normal as determined by qualified research center staff
- •Asymptomatic for genital infections at the time of enrollment
- •Willing to refrain from use of vaginal products or objects for 14 days prior to enrollment and for the duration of the trial.
- •Documentation of no abnormality on Pap smear within 90 days prior to randomization;
- •Willing to answer acceptability and adherence questionnaires throughout the trial
- •Willing to refrain from participation in any other research trial for the duration of this trial
- •Willing to provide adequate locator information for trial retention purposes and be reachable per local standard procedures
- •Willing to abstain from all the following criteria beginning 48 hours prior to each trial visit:
- •Vaginal intercourse
- •Oral contact with her genitalia
- •Internal vaginal washing
- •Penetration of the vagina by fingers, sex toys, or any other objects, including medications
- •Willing to abstain from all of the following for 3 days after biopsy procedures:
- •Vaginal intercourse
- •Oral contact with her genitalia
- •Internal vaginal washing
- •Penetration of the vagina by fingers, sex toys, or any other objects, including medications
排除标准
- •Currently pregnant or having had their last pregnancy outcome within 3 months prior to screening
- •Currently breast-feeding, or having breastfed within 3 months prior to screening
- •Receipt of any investigational agent within 60 days prior to screening
- •Previously participated in any HIV vaccine trial
- •Untreated urogenital infections within 2 weeks prior to enrollment
- •Presence of any abnormal physical finding on the vulva, vaginal walls or cervix during pelvic/speculum examination and/or colposcopy
- •History of significant urogenital or uterine prolapse, undiagnosed vaginal bleeding, or urethral obstruction
- •Pap smear result at screening that requires cryotherapy, biopsy or treatment (other than for infection)
- •History of symptomatic or asymptomatic HSV-2
- •Any Grade 2, 3 or 4 hematology, chemistry or urinalysis laboratory abnormality at baseline
- •Unexplained, undiagnosed abnormal bleeding per vagina during or following vaginal intercourse; or urogenital surgery within 90 days prior to enrollment
- •Any history of anaphylaxis or severe allergy resulting in angioedema; or a history of sensitivity/allergy to latex
- •Any serious acute, chronic or progressive disease
- •Any condition(s) that, in the opinion of the Investigator, might interfere with adherence to trial requirements or evaluation of the trial objectives
研究组 & 干预措施
dapivirine gel 4789
will be applied by participants once daily for 12-weeks treatment period
干预措施: dapivirine 4789 (Drug)
dapivirine gel 4759
Will be applied by participants once daily for12-weeks treatment period
干预措施: dapivirine gel 4759 (Drug)
HEC-based placebo gel, 2.5g containing no Dapivirine
Will be applied once daily for 12-weeks treatment period
干预措施: Drug placebo (Drug)
结局指标
主要结局
The Percentage of Women With the Composite Endpoint of Abnormal Safety Findings.
时间窗: 12 weeks
A composite endpoint was defined as the percentage of participants with any post-baseline abnormal finding from pelvic/speculum examination, colposcopy finding, STI diagnoses, laboratory test of DAIDS grade 3 or higher and any product-related AE. DAIDS severity grades are defined as follows: Grade 1 = mild Grade 2 = moderate Grade 3 = severe Grade 4 = potentially life-threatening Grade 5 = death
次要结局
- Changes in the Vaginal Flora(16 weeks)
- The Distribution of Dapivirine Levels Observed in Plasma Samples at Each Specified Time Point(12 weeks)
- The Adherence to Once Daily Application of a Vaginal Microbicide Gel Over a 12-week Period in Healthy, Sexually Active, HIV-negative Women(12 weeks)
- Changes in the Vaginal pH(12 weeks)
- The Distribution of Dapivirine Levels Observed in Vaginal Fluid at Each Specified Time Point.(12 weeks. Measured at 2, 4, and 8 weeks post-enrolment and at one of these at week 12; 24, 48, or 72 hours after gel discontinuation. (Participants were randomized to have vaginal fluid samples collected at one of these visits (5a, 5b, or 5c).)
- The Distribution of Dapivirine Levels Observed in Vaginal Tissue at Each Specified Time Point.(12 weeks. Measured at 2, 4, and 8 weeks post-enrolment and at one of these at week 12; 24, 48, or 72 hours after gel discontinuation. (Participants were randomized to have vaginal fluid samples collected at one of these visits (5a, 5b, or 5c).)
- Acceptability of Once Daily Application of a Vaginal Microbicide Gel Over a 12-week Period in Healthy, Sexually Active, HIV-negative Women(12 weeks)