An Expanded Safety Study of Dapivirine Gel 4759 in Africa

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). IPM014A is a Phase I/II study designed: (1) to assess and compare the safety of a once daily application of Dapivirine Gel 4759, 0.05% 2.5g and a matching vehicle placebo gel; (2) to assess the acceptability of a once daily application of Dapivirine gel 4759, 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.

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