Clinical trial NCT02858037: Trial to Assess the Continued Safety of and Adherence to a Vaginal Ring Containing Dapivirine in Women
Official title: A Phase 3B Open-Label Follow-on Trial to Assess the Continued Safety of and Adherence to a Vaginal Ring Containing Dapivirine in Women
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Human Immunodeficiency Virus
Lead sponsor: International Partnership for Microbicides, Inc.
Sponsor class: INDUSTRY
First posted: 2016-08-08
Enrollment: 1456
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention 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.
Primary purpose: PREVENTION

Brief summary: HIV Open-label Prevention Extension (HOPE).

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

Eligibility criteria: Inclusion Criteria:

Women must meet all of the following criteria to be eligible for inclusion in the study

1. Previously enrolled in MTN-020 (ASPIRE)
2. Able and willing to provide written informed consent to be screened for and to take part in the study
3. Able and willing to provide adequate locator information, as defined in site SOPs
4. HIV-uninfected based on testing performed by study staff at Screening and Enrollment
5. 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)
6. 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

1. Study product use permanently discontinued in response to an AE or safety related concern while taking part in the MTN-020 (ASPIRE) trial
2. Per participant report at Screening:

   1. Plans to relocate away from the study site during study participation
   2. Plans to travel away from the study site for more than three consecutive months during study participation
3. Per participant report at Enrollment, currently taking Post-Exposure Prophylaxis (PEP)
4. 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
5. Is pregnant at Screening/Enrollment or planning to become pregnant in the participant's anticipated study participation period
6. Currently breastfeeding
7. Diagnosed with urinary tract infection (UTI), pelvic inflammatory disease (PID), STI or reproductive tract infection (RTI) requiring treatment per WHO guidelines
8. 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
9. Has any of the following laboratory abnormalities at Screening Visit:

   1. Aspartate aminotransferase (AST) or alanine transaminase (ALT) \> Grade 3\*
   2. Creatinine \> Grade 3\*
   3. Hemoglobin \> Grade 3\*
   4. Platelet count \> Grade 3\*
   5. 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)
10. 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

    -

Primary outcomes:
measure: The Safety Profile Associated With the Open-label Use of the Dapivirine Vaginal Matrix Ring (25 mg) in Women
timeFrame: 13 months
measure: Adherence to the Open Label Use of the Dapivirine Vaginal Matrix Ring (25 mg) in Women
timeFrame: 13 months
Secondary outcomes:
measure: Incidence of HIV-1 Infection
timeFrame: 13 months
measure: Number of Participant Who Acquired HIV-1 With HIV-1 Drug Resistance Associated Mutations.
timeFrame: 13 months
Other outcomes:
Locations:
city: Blantyre
country: Malawi
facility: Johns Hopkins University Research Project
city: Lilongwe
country: Malawi
facility: Malawi Clinical Research Center
city: Westville
country: South Africa
facility: Medical Research Council of South Africa
state: Durban
city: Johannesburg
country: South Africa
facility: WRHI Clinical Research Center
state: Gauteng
city: Durban
country: South Africa
facility: Botha's Hill Clinical Research Center
state: Kwa-Zulu Natal
city: Durban
country: South Africa
facility: Chatsworth Clinical Research Center
state: Kwa-Zulu Natal
city: Durban
country: South Africa
facility: Verulam Clinical Research Center
state: KwaZulu-Natal
city: Durban
country: South Africa
facility: Isipingo Clinical Research Center
state: KwaZulu-Natal
city: Durban
country: South Africa
facility: Tongaat Clinical Research Center
state: KwaZulu-Natal
city: Cape Town
country: South Africa
facility: Emavundleni Research Centre
state: Western Cape
city: Durban
country: South Africa
facility: eThekwini Clinical Research Center
city: Johannesburg
country: South Africa
facility: Wits Reproductive Health and HIV Institute Research Centre
city: Kampala
country: Uganda
facility: Makerere University - Johns Hopkins University Research Collaboration Clinical Research Center
city: Kampala
country: Uganda
facility: MU-JHU Research Collaboration
city: Harare
country: Zimbabwe
facility: Seke South Clinical Research Center
city: Harare
country: Zimbabwe
facility: Spilhaus Clinical Research Center
city: Harare
country: Zimbabwe
facility: Zengeza Clinical Research Center
Study officials:
affiliation: International Partnership for Microbicides
name: John Steytler
role: STUDY_DIRECTOR
References:
citation: Baeten JM, Palanee-Phillips T, Mgodi NM, Mayo AJ, Szydlo DW, Ramjee G, Gati Mirembe B, Mhlanga F, Hunidzarira P, Mansoor LE, Siva S, Govender V, Makanani B, Naidoo L, Singh N, Nair G, Chinula L, Parikh UM, Mellors JW, Balan IC, Ngure K, van der Straten A, Scheckter R, Garcia M, Peda M, Patterson K, Livant E, Bunge K, Singh D, Jacobson C, Jiao Y, Hendrix CW, Chirenje ZM, Nakabiito C, Taha TE, Jones J, Torjesen K, Nel A, Rosenberg Z, Soto-Torres LE, Hillier SL, Brown ER; MTN-025/HOPE Study Team. Safety, uptake, and use of a dapivirine vaginal ring for HIV-1 prevention in African women (HOPE): an open-label, extension study. Lancet HIV. 2021 Feb;8(2):e87-e95. doi: 10.1016/S2352-3018(20)30304-0.
citation: Kutner BA, Giguere R, Lentz C, Kajura-Manyindo C, Dolezal C, Butheliezi S, Gwande M, Nampiira S, Ndlovu T, Mvinjelwa P, Mwenda W, Balan IC. Sharing Objective Measures of Adherence to a Vaginal Microbicide Promotes Candor About Actual Use and Bolsters Motivation to Prevent HIV. AIDS Behav. 2021 Mar;25(3):721-731. doi: 10.1007/s10461-020-03026-6. Epub 2020 Sep 12.