Clinical trial NCT02862171: To Assess Continued Safety of and Adherence to the Dapivirine (25 mg) Vaginal Ring-004 in Healthy, HIV-negative Women
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV Prevention
Lead sponsor: International Partnership for Microbicides, Inc.
Sponsor class: INDUSTRY
First posted: 2016-08-10
Enrollment: 941
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

Women must meet all the following criteria to be eligible to enrol in the trial:

1. Previously enrolled in the IPM 027 trial
2. Available for all visits and consent to follow all procedures scheduled for the trial
3. 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
4. HIV-negative as determined by the HIV algorithm applied at Screening/Pre- Enrolment
5. Willing to refrain from participation in another research trial using drugs, vaccines, medical devices and microbicides for the duration of the IPM 032 trial
6. 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:

1. 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
2. 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
3. Currently pregnant, intends to become pregnant or currently breast-feeding
4. Known drug abuse or alcohol dependence in the 12 months prior to screening
5. 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
6. 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

Primary outcomes:
measure: 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.
timeFrame: at least 12 months and up to 17 months
measure: Adherence to the Use of the 25 mg Dapivirine Vaginal Ring-004 Inserted at Monthly Intervals, in an Open-label Trial
timeFrame: at least 12 months and up to 17 months
Secondary outcomes:
measure: Incidence of HIV-1 Seroconversion
timeFrame: at least 12 months and up to 17 months
measure: Number of Participants Who Acquired HIV-1 With HIV-1 Drug Resistance-associated Mutations. Infection
timeFrame: at least 12 months and up to 17 months
Other outcomes:
Locations:
city: Ladysmith
country: South Africa
facility: Qhakaza Mbokodo
state: KZN
city: Pietermaritzburg
country: South Africa
facility: MatCH Research Unit
state: KZN
city: Brits
country: South Africa
facility: Madibeng Centre for Research
state: North West
city: Cape Town
country: South Africa
facility: Desmond Tutu HIV Foundation
state: Western Cape
city: Elandsdoorn
country: South Africa
facility: Ndlovu Medical Centre
city: Entebbe
country: Uganda
facility: MRC/UVRI Uganda Research Unit on AIDS
Study officials:
affiliation: International Partnership for Microbicides
name: John Steytler
role: STUDY_DIRECTOR
References:
citation: Nel A, van Niekerk N, Van Baelen B, Malherbe M, Mans W, Carter A, Steytler J, van der Ryst E, Craig C, Louw C, Gwetu T, Mabude Z, Kotze P, Moraba R, Tempelman H, Gill K, Kusemererwa S, Bekker LG, Devlin B, Rosenberg Z; DREAM Study Team. Safety, adherence, and HIV-1 seroconversion among women using the dapivirine vaginal ring (DREAM): an open-label, extension study. Lancet HIV. 2021 Feb;8(2):e77-e86. doi: 10.1016/S2352-3018(20)30300-3.