An Expanded Safety Study of Dapivirine Gel 4789 in Africa

Study Overview
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Brief Summary
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The purpose of this study is to determine whether dapivirine gel 4789 is safe for daily use by healthy women in South Africa.

Detailed Description
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To reduce the influence of adherence as a factor in the interpretation of efficacy results, IPM is considering using a DOT (Directly Observed Therapy) based method for vaginal microbicide gel delivery in a future Phase III study. IPM has denoted this DOT based method as Daily Monitored Adherence (DMA). IPM014B is a Phase I/II study designed: (1) to assess and compare the safety of a once daily application of Dapivirine Gel 4789, 0.05% 2.5g and a matching vehicle placebo gel; (2) to assess the acceptability of a once daily application of Dapivirine gel 4789, 0.05% 2.5g and a matching vehicle placebo gel; and (3) to assess the feasibility of utilizing the DMA method for a large-scale phase III efficacy study.

Official Title
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A Double-blind, Randomized, Placebo-Controlled Phase I/II Study to Evaluate the Safety and Acceptability of Dapivirine Gel 4789, 0.05%, 2.5g, a Vaginal Microbicide, Conducted Using Daily Monitored Adherence in Healthy, HIV-Negative Women.

Conditions
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HIV Infections, Acquired Immunodeficiency Syndrome, Healthy

Intervention / Treatment
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* Drug: dapivirine
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 study Agree to daily application of gel and monitoring as per Daily Monitored Adherence (DMA) method Healthy and self-reported sexually active HIV-negative as determined by a HIV rapid test at time of enrollment On a stable form of contraception and willing to continue on this stable method of contraception, OR, Have undergone surgical sterilisation at least 3 months prior to enrollment 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 36 days between menses Upon pelvic/speculum examination and colposcopy at the time of enrollment, the cervix and vagina appear normal as determined by the investigator Asymptomatic for genital infections at the time of enrollment Willing to refrain from use of vaginal products or objects within 14 days prior to enrollment and for the duration of the study Willing to answer acceptability and adherence questionnaires throughout the study Willing to refrain from participation in any other research study for the duration of this study Willing to provide adequate locator information for study retention purposes and be reachable per local standard procedures Exclusion Criteria: Currently pregnant or last pregnancy outcome within 3 months prior to enrolment Currently breast-feeding Participated in any other research study within 60 days prior to screening Previously participated in any HIV vaccine study Untreated urogenital infections (either symptomatic or asymptomatic) within 2 weeks prior to enrollment Presence of 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, urethral obstruction Pap smear result at screening that requires cryotherapy, biopsy, treatment (other than for infection), or further evaluation Any Grade 2, 3 or 4 baseline haematology, chemistry or urinalysis laboratory abnormality according to the DAIDS Table for Grading Adverse Experiences Unexplained, undiagnosed abnormal bleeding per vagina, bleeding per vagina during or following vaginal intercourse, or gynaecologic 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 study requirements or evaluation of the study objectives

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: vehicle placebo gel<br> | Drug: placebo<br>* dosage form: vaginal gel frequency: once daily duration: 6 weeks<br>|
| Experimental: dapivirine gel<br> | Drug: dapivirine<br>* dosage form: vaginal gel dosage: 1.25mg dapivirine/day frequency: once daily duration: 6 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gynaecological examinations, including pelvic/speculum examination and colposcopy, and laboratory STI testing. |  | Week 0, 1, 2, 4, 6 & 10 | 
| Safety laboratory tests |  | enrollment & last day of gel use | 
| Adverse event/serious adverse event reports |  | throughout study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Questionnaires concerning acceptability and adherence to daily use of vaginal gel. |  | Week 0, 2, 6 & 10 | 
| Documentation of adherence to the DMA method including the Applicator Collection Checklist, focus groups and male interviews. |  | throughout study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV Infections, Acquired Immunodeficiency Syndrome, Healthy, HIV seronegativity