Trial to Assess the Continued Safety of and Adherence to a Vaginal Ring Containing Dapivirine in Women

Study Overview
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Brief Summary
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HIV Open-label Prevention Extension (HOPE).

Detailed Description
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A Phase 3B Open-Label Follow-on Trial to Assess the Continues Safety of and Adherence to a Vaginal ring Containing Dapivirine in Women

Official Title
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A Phase 3B Open-Label Follow-on Trial to Assess the Continued Safety of and Adherence to a Vaginal Ring Containing Dapivirine in Women

Conditions
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Human Immunodeficiency Virus

Intervention / Treatment
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* Combination Product: Dapivirine Vaginal Ring


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women must meet all of the following criteria to be eligible for inclusion in the study Previously enrolled in MTN-020 (ASPIRE) Able and willing to provide written informed consent to be screened for and to take part in the study Able and willing to provide adequate locator information, as defined in site SOPs HIV-uninfected based on testing performed by study staff at Screening and Enrollment Using an effective method of contraception at Enrollment, and intending to use an effective method for the duration of study participation; effective methods include hormonal methods (except contraceptive ring); intrauterine contraceptive device (IUCD); and sterilization (of participant, as defined in site SOPs) At Screening and Enrollment, agrees not to participate in other research studies involving drugs, medical devices, vaginal products, or vaccines for the duration of study participation Exclusion Criteria: Women who meet any of the following criteria will be excluded from the study Study product use permanently discontinued in response to an AE or safety related concern while taking part in the MTN-020 (ASPIRE) trial Per participant report at Screening: Plans to relocate away from the study site during study participation Plans to travel away from the study site for more than three consecutive months during study participation Per participant report at Enrollment, currently taking Post-Exposure Prophylaxis (PEP) With the exception of MTN-020 (ASPIRE), participation in any other research study involving drugs, medical devices, vaginal products, or vaccines, within 60 days of enrollment Is pregnant at Screening/Enrollment or planning to become pregnant in the participant's anticipated study participation period Currently breastfeeding Diagnosed with urinary tract infection (UTI), pelvic inflammatory disease (PID), STI or reproductive tract infection (RTI) requiring treatment per WHO guidelines At Screening, has a clinically apparent Grade 3 pelvic exam finding (observed by study staff) as per the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events Version 1.0, December, 2004 (Clarification dated August 2009), Addendum 1-Female Genital Grading Table for Use in Microbicide Studies Has any of the following laboratory abnormalities at Screening Visit: Aspartate aminotransferase (AST) or alanine transaminase (ALT) > Grade 3* Creatinine > Grade 3* Hemoglobin > Grade 3* Platelet count > Grade 3* Pap result ≥ Grade 3 according to the Female Genital Grading Table for Use in Microbicide Studies Addendum 1 to the DAIDS Table for Grading Adult and Pediatric Adverse Events, Version 1.0, December 2004 (Clarification dated August 2009) Has any significant medical condition or other condition that, in the opinion of the IoR/designee, would preclude informed consent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving 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
Intervention Model: Single Group Assignment
Interventional Model Description: Participants will receive a silicone elastomer vaginal matrix ring containing 25 mg of dapivirine to be replaced each month for a total period of 12 months of use.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HIV Open-label Prevention<br>Following demonstration of safety and efficacy of the dapivirine vaginal ring in MTN-020, eligible MTN-020 participants will be offered enrollment into MTN-025, a trial designed to obtain additional safety and adherence data in women MTN-020:NCT01617096 MTN-025: NCT02858037 | Combination Product: Dapivirine Vaginal Ring<br>* Dapivirine Vaginal Ring, 25 ring given monthly for at least one year.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Safety Profile Associated With the Open-label Use of the Dapivirine Vaginal Matrix Ring (25 mg) in Women | Number of participants Grade 2, Grade 3, and all serious Adverse Events. | 13 months | 
| Adherence to the Open Label Use of the Dapivirine Vaginal Matrix Ring (25 mg) in Women | By measuring the residual levels of dapivirine in returned used vaginal rings. | 13 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of HIV-1 Infection | HIV-1 infection as measured by the protocol algorithm | 13 months | 
| Number of Participant Who Acquired HIV-1 With HIV-1 Drug Resistance Associated Mutations. | HIV-1 drug resistance mutations among participants who acquire HIV-1, as measured by standard genotype analysis and more sensitive methods to detect low frequency drug-resistant variants | 13 months |