A Safety and Efficacy Trial of Dapivirine Vaginal Ring in Africa

Study Overview
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Brief Summary
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This is a double-blind, randomized, placebo-controlled Phase III study to assess the safety and efficacy of a silicone elastomer vaginal ring containing 25mg of dapivirine.

Official Title
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A Multi-Centre, Randomised, Double-Blind, Placebo-Controlled Phase III Safety and Efficacy Trial of a Vaginal Matrix Ring With Dapivirine for the Prevention of HIV-1 Infection in Women

Conditions
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HIV Infections

Intervention / Treatment
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* Other: Dapivirine
* Other: Placebo
* Drug: Dapivirine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women >18 and <40 years of age who can provide informed consent Available for all visits and consent to follow all procedures scheduled for the trial Generally healthy and self-reported sexually active (defined as an average of at least one penetrative penile vaginal coital act per month for the last 3 months prior to enrolment) HIV-negative as determined by the HIV algorithm applied at screening and enrolment On a stable form of contraception as defined within section 5.4 and willing to continue on stable contraception for the duration of the clinical trial; Asymptomatic for genital infections at the time of enrolment (if a woman is diagnosed with any clinically significant treatable STI, she must have initiated treatment at least 1 week prior to enrolment and have completed the full course of treatment) Willing to answer questions about adherence, sexual behaviour, vaginal practices and ring acceptability; Willing to provide adequate locator information for trial retention purposes and be reachable per local standard procedures (e.g., by home visit or telephone; or via family or close neighbour contacts [confidentiality to be maintained]) Willing to refrain from participation in another research trial using drugs, vaccines, medical devices, microbicides or oral pre-exposure prophylaxis investigational drugs for the duration of the IPM 009A trial; In the absence of the use of exogenous hormone(s), have a self-reported regular menstrual cycle defined as having a minimum of 21 days and a maximum of 35 days between menses; Willing to refrain from use of vaginal products or objects including spermicides, tampons, female condoms, cotton wool, rags, diaphragms, cervical caps (or any other vaginal barrier method), douches and drying agents within 14 days from enrolment and for the duration of the trial. Exclusion Criteria: Currently pregnant or last pregnancy within 3 months prior to screening; Currently breast-feeding Participated in another research trial using drugs, medical devices, microbicides or oral pre-exposure prophylaxis agents within 60 days prior to screening Previously participated or currently participating in any HIV vaccine trial Untreated, clinically significant urogenital infections (either symptomatic or asymptomatic), e.g., urinary tract or other sexually transmitted infections, or other gynaecological symptoms within 1 week prior to enrolment History of significant urogenital or uterine prolapse, undiagnosed vaginal bleeding, urethral obstruction, incontinence or urge incontinence Any gynaecological surgery within 90 days prior to enrolment Any Grade 3 or 4 baseline haematology, chemistry or urinalysis laboratory value according to the DAIDS Table for Grading Adverse Experiences, or clinically significant Grade 2 findings Any history of anaphylaxis or severe allergy resulting in angioedema; or a history of sensitivity/allergy to latex or a silicone elastomer Any history of diabetes mellitus and chronic use of oral steroid therapy and any uncontrolled serious chronic or progressive disease Cervical cytology at screening that requires cryotherapy, biopsy, treatment (other than for infection), or further evaluation [this includes any findings of atypical squamous cells of undetermined significance (ASCUS)] Any condition(s) that, in the opinion of the investigator, might put the participant at risk, or interfere with the trial objectives, or adherence to trial requirements

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dapivirine<br>Vaginal ring containing 25mg of dapivirine | Other: Dapivirine<br>* Vaginal ring containing 25mg dapivirine; one ring inserted every 28 days for at least 15 months<br>Drug: Dapivirine<br> <br> |
| Placebo Comparator: Placebo Ring<br>Vaginal ring containing no drug substance | Other: Placebo<br>* Vaginal Ring containing no drug substance<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy as determined by the proportion of women in each arm HIV-1 seroconversion rate per person-years of product use, measured at the end of the investigational product use period. | The primary endpoint is HIV-1 seroconversion measured by rapid and specialized laboratory tests according to a comprehensive HIV testing algorithm. This algorithm employs a series of high specificity and high sensitivity immunoassay-based HIV blood tests that minimize the chance of false positive results to determine if a subject is positive for HIV. Endpoint confirmation of HIV infection is by Western blot. | 15 months | 
| Safety as determined by grade 3 and 4 AE's, clinically significant grade 2 laboratory findings (based on DAIDS grading) and all serious AE's. | This will be measured by self-reports, physical examination, safety laboratory tests and other specialised investigations. | 15 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adherence to the protocol-specific product regimen as determined by self-reported diary cards and questionnaires. |  | 15 months | 
| The incidence of curable STI's or pregnancy as determined by STI testing and pregnancy testing. |  | 15 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV Infections, Anti-HIV agents, HIV-1