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CompletedNCT02858037Updated Oct 25, 2022Results posted

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

A Phase 3 interventional study of Dapivirine Vaginal Ring in Human Immunodeficiency Virus, sponsored by International Partnership for Microbicides, Inc.. Completed at 17 sites in 4 countries. Open to female participants aged 18 Years to 40 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2022-10-25.

Sponsored by International Partnership for Microbicides, Inc. · Phase 3, Interventional, and Prevention

Phase
Phase 3
Study type
Interventional
Enrollment
1,456
Allocation
Not applicable
Ages
18 Years to 40 Years
Sex
Female
01

Study summary

HIV Open-label Prevention Extension (HOPE).

Read the 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

02

Conditions studied

  • Human Immunodeficiency Virus
03

Who can participate

Ages eligible
18 Years to 40 Years
Sexes eligible
Female
Accepts healthy volunteers
Yes

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

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

    -

04

Study design

Phase
Phase 3
Primary purpose
Prevention
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
1,456 participants (actual)

Study arms

  • 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

Interventions

  • Combination productDapivirine Vaginal Ring

    Dapivirine Vaginal Ring, 25 ring given monthly for at least one year.

05

What researchers measure

Primary outcomes

  1. 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.

    Time frame: 13 months

  2. 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.

    Time frame: 13 months

Secondary outcomes

  1. Incidence of HIV-1 Infection

    HIV-1 infection as measured by the protocol algorithm

    Time frame: 13 months

  2. 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

    Time frame: 13 months

06

Results

Posted Oct 25, 2022
Limitations and caveats
Interpretation of the HIV-1 incidence rates is limited by the lack of a concurrent placebo group in MTN-025. Dapivirine residual levels in returned used rings do not provide adherence information at the time of potential exposure to and infection with HIV, eg, if a participant temporarily removes the DVR during sexual intercourse.

Participant flow

MTN-025 was implemented as a follow-on trial to MTN-020, and the inclusion and exclusion criteria were used to ensure the appropriate selection of trial participants for MTN-025. The Decliner Population were former MTN-020 participants who declined participation in the main MTN-025 trial, and who met the inclusion and exclusion criteria Women in the Decliner Population were invited to complete a single visit which consisted of behavioral assessments.

Participant flow — Overall Study
MilestoneHIV Open-label Prevention
Started1456
Exposed primary cohort1368
Completed1404
Not completed52
Withdrew: Death1
Withdrew: Withdrawal by subject18
Withdrew: Participant relocated, no follow-up planned26
Withdrew: Lost to follow-up3
Withdrew: Other4

Outcome measures

PrimaryThe 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.

Time frame:
13 months
Reported as:
Count of participants · Participants
The Safety Profile Associated With the Open-label Use of the Dapivirine Vaginal Matrix Ring (25 mg) in Women
ParticipantsHIV Open-label Prevention
At least one Grade 3 or higher AE52
At least one serious AE19
At least one grade 2 or higher related AE2
PrimaryAdherence 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.

Time frame:
13 months
Reported as:
Mean · mg
Adherence to the Open Label Use of the Dapivirine Vaginal Matrix Ring (25 mg) in Women
mgHIV Open-label Prevention
Enrollment21.0 (17.7 to 25.9)
Month 121.1 (17.0 to 26.3)
Month 221.0 (16.5 to 27.1)
Month 321.1 (16.4 to 27.8)
Month 621.2 (16.6 to 27.3)
Month 921.3 (15.8 to 27.1)
SecondaryIncidence of HIV-1 Infection

HIV-1 infection as measured by the protocol algorithm

Time frame:
13 months
Reported as:
Number · events per 100 person-years
Incidence of HIV-1 Infection
events per 100 person-yearsHIV Open-label Prevention
Incidence of HIV-1 Infection2.7
SecondaryNumber 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

Time frame:
13 months
Reported as:
Count of participants · Participants
Number of Participant Who Acquired HIV-1 With HIV-1 Drug Resistance Associated Mutations.
ParticipantsHIV Open-label Prevention
Number of Participant Who Acquired HIV-1 With HIV-1 Drug Resistance Associated Mutations.6

Adverse events

Collected over 13 months. Non-serious events are listed at a 2% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
HIV Open-label Prevention1/1,368 (0.1%)19/1,368 (1.4%)844/1,368 (61.7%)
Most frequent serious events
Showing 10 of 20
Most frequent serious events
EventHIV Open-label Prevention
GastrtitisGastrointestinal disorders1/1368
Pelvic Inflammatory DiseaseInfections and infestations1/1368
PneummoniaInfections and infestations1/1368
Respiratory Track InfectionInfections and infestations1/1368
Subcutaneous abscessInfections and infestations1/1368
Animal BiteInjury, poisoning and procedural complications1/1368
ContusionInjury, poisoning and procedural complications1/1368
Head injuryInjury, poisoning and procedural complications1/1368
Multiple injuriesInjury, poisoning and procedural complications1/1368
Tendon injuryInjury, poisoning and procedural complications1/1368
Most frequent other events
Showing 10 of 14
Most frequent other events
EventHIV Open-label Prevention
Genitourinary chlamydia infectionInfections and infestations115/1368
Vaginal dischargeReproductive system and breast disorders110/1368
Vulvovaginitis trichomonalInfections and infestations81/1368
Urinary Tract InfectionInfections and infestations71/1368
Bacteria vaginosisInfections and infestations70/1368
Upper respiratory tract infectionInfections and infestations67/1368
Vulvovaginal CandidiasisInfections and infestations65/1368
Genitourinary tract gonococcal infectionInfections and infestations58/1368
Vulvovaginal pruritusReproductive system and breast disorders54/1368
Pelvic painReproductive system and breast disorders45/1368

Baseline characteristics

Age, Continuous
Age, Continuous(Years)HIV Open-label Prevention
Mean32.0 ± 6.51
Sex: Female, Male
Sex: Female, Male(Participants)HIV Open-label Prevention
Female1456
Male0
Race (NIH/OMB)
Race (NIH/OMB)(Participants)HIV Open-label Prevention
American Indian or Alaska Native0
Asian8
Native Hawaiian or Other Pacific Islander0
Black or African American1276
White0
More than one race88
Unknown or Not Reported84
Region of Enrollment
Region of Enrollment(participants)HIV Open-label Prevention
Malawi157
South Africa705
Uganda172
Zimbabwe422
Marital Status
Marital Status(Participants)HIV Open-label Prevention
Not Married770
Married686
07

Study locations

17 sites
  • Johns Hopkins University Research Project
    Blantyre, Malawi
  • Malawi Clinical Research Center
    Lilongwe, Malawi
  • Medical Research Council of South Africa
    Westville, Durban 3630, South Africa
  • WRHI Clinical Research Center
    Johannesburg, Gauteng, South Africa
  • Botha's Hill Clinical Research Center
    Durban, Kwa-Zulu Natal, South Africa
  • Chatsworth Clinical Research Center
    Durban, Kwa-Zulu Natal, South Africa
  • Verulam Clinical Research Center
    Durban, KwaZulu-Natal 4340, South Africa
  • Isipingo Clinical Research Center
    Durban, KwaZulu-Natal, South Africa
  • Tongaat Clinical Research Center
    Durban, KwaZulu-Natal, South Africa
  • Emavundleni Research Centre
    Cape Town, Western Cape 7750, South Africa
  • eThekwini Clinical Research Center
    Durban, 4001, South Africa
  • Wits Reproductive Health and HIV Institute Research Centre
    Johannesburg, South Africa
  • Makerere University - Johns Hopkins University Research Collaboration Clinical Research Center
    Kampala, Uganda
  • MU-JHU Research Collaboration
    Kampala, Uganda
  • Seke South Clinical Research Center
    Harare, Zimbabwe
  • Spilhaus Clinical Research Center
    Harare, Zimbabwe
  • Zengeza Clinical Research Center
    Harare, Zimbabwe
08

References and documents

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. PubMed 33539762 ↗
  • 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. PubMed 32920652 ↗

Study documents

  • Study protocol · Nov 11, 2016
  • Statistical analysis plan · May 28, 2021

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Undecided

09

Registry details

Key details

Study ID
NCT02858037
Lead sponsor
International Partnership for Microbicides, Inc.
Responsible party
Sponsor
First posted
Aug 8, 2016
Start date
Jul 18, 2016
Primary completion
Oct 10, 2018
Completion
Oct 10, 2018
Results posted
Oct 25, 2022
Last update
Oct 25, 2022

Study contacts

John Steytler
study director · International Partnership for Microbicides

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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