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

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

HIV Open-label Prevention Extension (HOPE).

Study Overview

• Status: Completed
• Conditions: Human Immunodeficiency Virus
• Intervention / Treatment: Combination product: Dapivirine Vaginal Ring

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

• Study Type: Interventional
• Enrollment (Actual): 1456
• Phase: Phase 3

Contacts and Locations

Study Locations

• Malawi
  • Blantyre, Malawi
    • Johns Hopkins University Research Project
  • Lilongwe, Malawi
    • Malawi Clinical Research Center
• South Africa
  • Durban, South Africa, 4001
    • eThekwini Clinical Research Center
  • Johannesburg, South Africa
    • Wits Reproductive Health and HIV Institute Research Centre
  • Durban
    • Westville, Durban, South Africa, 3630
      • Medical Research Council of South Africa
  • Gauteng
    • Johannesburg, Gauteng, South Africa
      • WRHI Clinical Research Center
  • Kwa-Zulu Natal
    • Durban, Kwa-Zulu Natal, South Africa
      • Botha's Hill Clinical Research Center
    • Durban, Kwa-Zulu Natal, South Africa
      • Chatsworth Clinical Research Center
  • KwaZulu-Natal
    • Durban, KwaZulu-Natal, South Africa, 4340
      • Verulam Clinical Research Center
    • Durban, KwaZulu-Natal, South Africa
      • Isipingo Clinical Research Center
    • Durban, KwaZulu-Natal, South Africa
      • Tongaat Clinical Research Center
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7750
      • Emavundleni Research Centre
• Uganda
  • Kampala, Uganda
    • Makerere University - Johns Hopkins University Research Collaboration Clinical Research Center
  • Kampala, Uganda
    • MU-JHU Research Collaboration
• Zimbabwe
  • Harare, Zimbabwe
    • Seke South Clinical Research Center
  • Harare, Zimbabwe
    • Spilhaus Clinical Research Center
  • Harare, Zimbabwe
    • Zengeza Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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

    -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: HIV Open-label Prevention; 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; Dapivirine Vaginal Ring, 25 ring given monthly for at least one year.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: International Partnership for Microbicides, Inc.

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 18, 2016
• Primary Completion (ACTUAL): October 10, 2018
• Study Completion (ACTUAL): October 10, 2018

Study Registration Dates

• First Submitted: July 18, 2016
• First Submitted That Met QC Criteria: August 5, 2016
• First Posted (ESTIMATE): August 8, 2016

Study Record Updates

• Last Update Posted (ACTUAL): October 25, 2022
• Last Update Submitted That Met QC Criteria: October 24, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Dapivirine
• Other Study ID Numbers: MTN-025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No