To Assess Continued Safety of and Adherence to the Dapivirine (25 mg) Vaginal Ring-004 in Healthy, HIV-negative Women

Study Overview
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Brief Summary
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A follow-on, open label trial to assess continued safety of and adherence to the Dapivirine(25mg) vaginal ring-004 in healthy, HIV-negative women

Detailed Description
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Phase IIIb, multicenter follow-on open-label trial to evaluate the continued adherence to and safety of the DVR, inserted at monthly intervals by healthy, HIV negative women who had participated in the IPM 027 Phase III DVR trial. All women who participated in IPM 027 (NCT 01539226) and were HIV-negative at screening for IPM 032, were eligible. Participants who provided written informed consent at screening were invited to undergo screening assessments for the trial. The Enrollment Visit had to occur within 45 days after the Screening Visit. Note: In the event that participation in IPM 027 was stopped prematurely and IPM 032 was activated at the RC, the IPM 027 Last Product Use Visit (LPUV) and the IPM 032 Screening and Enrollment Visits could be combined for participants who were eligible to enroll in IPM 032. All participants received the DVR containing 25 mg dapivirine at the Enrollment Visit, and attended a visit at the RC, 1 month after enrollment. Following this visit, a participant could continue on a 3 monthly visit schedule, at the Investigator's discretion. Monthly visits could, however, be extended up to the first 3 months of participation. From then on, all participants needed to switch to a 3-monthly schedule. Once the 3-monthly trial visit schedule commenced, three rings were dispensed at each visit. One ring was self-inserted at the RC and two additional rings were dispensed for the participant to take home, or dispensing took place as arranged with the participant. The protocol made provision for at least 12 months of DVR use (with the LPUV scheduled at Month 12), which could also have been extended. Participants could continue with ring use past Month 12 and the RCs could continue scheduling the 3-monthly visits as per the participant visit schedule. Exit Visits of participants who completed 12 months or more on the trial commenced in October 2017 and ended in January 2019. Participants who were still enrolled in the trial in October 2017 and those who had been enrolled at a later stage in the trial were scheduled to attend the Month 12 Visit, irrespective of their visit schedule assignments. Exit Visits were then scheduled as per protocol, ie, 1 to 2 months after the Month 12 Visit. Exit Visits were optional for participants who discontinued early from the trial. Adherence assessments included analysis of dapivirine residual levels in returned used rings, correlation analysis of dapivirine residual levels with visual inspection of used rings, and self-reported acceptability and adherence. The HIV-1 incidence and the occurrence of HIV-1 drug resistance were assessed using HIV rapid testing and genotyping, respectively. Social and behavioral parameters were assessed qualitatively and quantitatively. Quantitative assessments included evaluation of the feasibility of 3-monthly follow-up visits and evaluation of the proportion of participants undergoing unscheduled HIV rapid tests (ie, in between the scheduled 3 monthly follow-up visits). Safety assessments included adverse event (AE) reporting, safety laboratory assessments, pregnancy testing, physical examination, vital sign assessments, pelvic examination, sexually transmitted infection (STI) tests, cervical cytology, and assessments of social harms. Throughout the trial, all participants received pre- and post-test HIV counseling, HIV/STI risk reduction counseling, and contraceptive, condom and vaginal ring adherence counseling.

Official Title
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A Follow-On, Open-Label Trial To Assess Continued Safety Of And Adherence To The Dapivirine (25 Mg) Vaginal Ring-004 In Healthy, HIV-Negative Women

Conditions
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HIV Prevention

Intervention / Treatment
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* Drug: Dapivirine Vaginal Ring-004


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women must meet all the following criteria to be eligible to enrol in the trial: Previously enrolled in the IPM 027 trial Available for all visits and consent to follow all procedures scheduled for the trial Using an effective method of contraception at the Enrolment Visit, and intending to use an effective contraceptive method for the duration of trial participation, unless post-menopausal with no history of menses for one year prior to screening HIV-negative as determined by the HIV algorithm applied at Screening/Pre- Enrolment Willing to refrain from participation in another research trial using drugs, vaccines, medical devices and microbicides for the duration of the IPM 032 trial 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. Exclusion Criteria: Women who meet any of the following criteria are NOT eligible to enrol in the trial: Investigational product use permanently discontinued in response to an AE (where the AE was considered related to investigational product) or safety-related concern while taking part in the IPM 027 trial Participant self-report of taking post-exposure prophylaxis (PEP) within ≤ 2 months at Screening Visit Note: Participants may be enrolled after completing the PEP regimen and a negative HIV test was documented at least 2 months prior to screening for IPM 032 Currently pregnant, intends to become pregnant or currently breast-feeding Known drug abuse or alcohol dependence in the 12 months prior to screening Participated in another research trial (other than IPM 027) using drugs, medical devices, microbicides or oral pre-exposure prophylaxis agents within 30 days prior to screening Any new illness or condition(s), chronic condition(s) or abnormal laboratory finding(s) that, in the opinion of the investigator, might put the participant at risk, or interfere with the trial objectives or the participant's 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dapivirine Vaginal Ring-004<br>Dapivirine Vaginal Ring, 25 mg.Each participant will engage in the screening process for up to 45 days prior to enrolment and will use the monthly Dapivirine Vaginal Ring for a period of up to 12 months. IPM will have the option to extend this trial period. | Drug: Dapivirine Vaginal Ring-004<br>* To assess the safety profile of the 25 mg Dapivirine Vaginal Ring-004, when inserted at monthly intervals, in an open-label trial<br>* Other names: TMC-120;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Safety Profile of the 25 mg Dapivirine Vaginal Ring-004, When Inserted at Monthly Intervals. Participants Attended RC at Monthly Visits (up to Max of Three Monthly Visits) Followed by 3-monthly Follow-up Visits. | Safety assessments included adverse event (AE) reporting; all product-related AEs, Grade 3 or 4 AEs, SAEs. | at least 12 months and up to 17 months | 
| Adherence to the Use of the 25 mg Dapivirine Vaginal Ring-004 Inserted at Monthly Intervals, in an Open-label Trial | Determined dapivirine residual amounts in returned used vaginal rings. | at least 12 months and up to 17 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of HIV-1 Seroconversion | Rapid and specialised laboratory testing according to a pre-specified HIV testing algorithm | at least 12 months and up to 17 months | 
| Number of Participants Who Acquired HIV-1 With HIV-1 Drug Resistance-associated Mutations. Infection | Viral genotype (including NGS) resistance testing methods which include sensitive methods to detect low frequency drug-resistant variants. | at least 12 months and up to 17 months |