- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01617096
Phase 3 Safety and Effectiveness Trial of Dapivirine Vaginal Ring for Prevention of HIV-1 in Women (ASPIRE)
A Multi-Center, Randomized, Double-Blind, Placebo-Controlled Phase 3 Safety and Effectiveness Trial of a Vaginal Matrix Ring Containing Dapivirine for the Prevention of HIV-1 Infection in Women
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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Blantyre, Malawi
- College of Medicine - Johns Hopkins University Research Project
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Lilongwe, Malawi
- UNC Project
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Cape Town, South Africa
- Desomond Tutu HIV Center
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Johannesburg, South Africa
- Wits Reproductive Health and HIV Institute
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KwaZulu-Natal
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Durban, KwaZulu-Natal, South Africa
- CAPRISA, eThekwini Clinical Research Site
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Kampala, Uganda
- MU-JHU Care LTD, MU-JHU Research Collaboration
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Harare
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Belgravia, Harare, Zimbabwe
- UZ-Obstetrics & Gynecology Research Clinic at Spillhaus
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Age 18 through 45 years (inclusive) at screening, verified per site SOPs; within this range, sites may restrict the upper age limit per site SOPs, to target women at high risk of HIV infection
- 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 (per applicable algorithm in Appendix II)
- Per participant report, sexually active, defined as having vaginal intercourse at least once in the 3 months prior to screening
- 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 device (IUD); 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 -- Note: Tampons may be used for the duration of the trial.
Exclusion Criteria:
Per participant report at screening:
- Intends to become pregnant during study participation
- Plans to relocate away from the study site during study participation
- Plans to travel away from the study site for more than 8 consecutive weeks during study participation
Is pregnant
-- Note: A documented negative pregnancy test performed by study staff is required for inclusion; however a self-reported pregnancy is adequate for exclusion from the study.
- Currently breastfeeding
Diagnosed with urinary tract infection (UTI)
-- Note: Otherwise eligible participants diagnosed with UTI during screening are offered treatment and may be enrolled after completing treatment and all symptoms have resolved. If treatment is completed and symptoms have resolved within 28 days of obtaining informed consent for screening, the participant may be enrolled.
Diagnosed with pelvic inflammatory disease, an STI or reproductive tract infection (RTI) requiring treatment per current WHO guidelines
-- Note: Otherwise eligible participants diagnosed during screening with pelvic inflammatory disease or STI/RTI requiring treatment per WHO guidelines - other than asymptomatic BV and asymptomatic candidiasis - are offered treatment and may be enrolled after completing treatment and all symptoms have resolved. If treatment is completed and symptoms have resolved within 28 days of obtaining informed consent for screening, the participant may be enrolled. Genital warts requiring treatment also must be treated prior to enrollment. Genital warts requiring therapy are defined as those that cause undue burden or discomfort to the participant, including bulky size, unacceptable appearance, or physical discomfort.
Has a clinically apparent Grade 2 or higher 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
- Note: Cervical bleeding associated with speculum insertion and/or specimen collection judged to be within the range of normal according to the clinical judgment of the Investigator of Record (IoR)/designee is considered expected non-menstrual bleeding and is not exclusionary.
- Note: Otherwise eligible participants with exclusionary pelvic exam findings may be enrolled/randomized after the findings have improved to a non-exclusionary severity grading or resolved. If improvement to a non-exclusionary grade or resolution is documented within 28 days of providing informed consent for screening, the participant may be enrolled.
Participant report and/or clinical evidence of any of the following:
- Known adverse reaction to any of the study products (ever)
- Known adverse reaction to latex (ever)
- Chronic vaginal candidiasis
- Non-therapeutic injection drug use in the 12 months prior to Screening
- Post-exposure prophylaxis (PEP) for HIV exposure within 6 months prior to enrollment
- Last pregnancy outcome 90 days or less prior to enrollment
- Gynecologic or genital procedure (e.g., tubal ligation, dilation and curettage, piercing) 90 days or less prior to enrollment
- Recent participation in any other research study involving drugs, medical devices, vaginal products, or vaccines, within 60 days of enrollment
- Participation in the MTN-003, Vaginal and Oral Interventions to Control the Epidemic (VOICE) clinical trial, or any other HIV prevention study using systemic or topical antiretroviral medications, within 12 months of enrollment
- As determined by the IoR/designee, any significant uncontrolled active or chronic cardiovascular, renal, liver, hematologic, neurologic, gastrointestinal, psychiatric, endocrine, respiratory, immunologic disorder or infectious disease, including active tuberculosis
Has any of the following laboratory abnormalities at Screening Visit:
- Aspartate aminotransferase (AST) or alanine transaminase (ALT) Grade 1 or higher 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)
- Creatinine Grade 2 or higher 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)
- Hemoglobin Grade 2 or higher 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)
- Platelet count Grade 1 or higher 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)
Pap result Grade 2 or higher 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)
- Note: Otherwise eligible participants with an exclusionary test may be re-tested during the screening process.
- Note: Women with a documented normal result within the 12 months prior to enrollment need not have Pap smear during the screening period. Women with a Grade 1 abnormal Pap smear can be enrolled upon completion of the initial phase of evaluation if no current treatment is indicated (based on local standard of care for management of abnormal cervical cytology). Need for a repeat Pap within 6 months does not preclude enrollment prior to that result becoming available.
- Has any 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: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Dapivirine Vaginal Ring
Vaginal ring containing 25mg dapivirine
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Dosage form: vaginal ring Dosage: 25mg Frequency: monthly Duration: 12 months
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Placebo Comparator: Placebo Ring
Vaginal ring containing no drug substance
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Vaginal ring containing no drug substance
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Efficacy as Determined by the Proportion of Women in Each Arm With HIV-1 Seroconversion After 120 Endpoints Are Observed in the Trial.
Time Frame: minimum of 12 months and a maximum of 14 months per participant
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The primary endpoint is HIV-1 seroconversion as measured by rapid and specialised laboratory testing according to comprehensive HIV testing algorithm.
Endpoint confirmation of HIV infection is by Western Blot.
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minimum of 12 months and a maximum of 14 months per participant
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The Number of Participants That Experienced Grade 2, 3, 4 and Serious Adverse Events Over the Investigational Product Used Period (25 mg Dapivirine Administered in a Silicone Elastomer Vaginal Matrix Ring (DVR), Inserted Once Every 4 Weeks).
Time Frame: minimum of 12 months and a maximum of 14 months per participant
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Participants with grade 2 adverse events, judged to be related to investigational product, grade 3 and grade 4 adverse events and all serious adverse events. DAIDS severity grades are defined as follows: Grade 1 = mild Grade 2 = moderate Grade 3 = severe Grade 4 = potentially life-threatening Grade 5 = death |
minimum of 12 months and a maximum of 14 months per participant
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Adherence to the Dapivirine Vaginal Ring.
Time Frame: 12 months per participant
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Dapivirine residual levels in used rings and dapivirine plasma concentrations are two objective measures of adherence to DVR ring use. Adherence was defined as a dapivirine ring residual level <=23.5 mg and dapivirine plasma level >= 95 pg/mL. |
12 months per participant
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Acceptability of the DVR and Placebo Vaginal Ring
Time Frame: 12 months per participant
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Questionnaires and qualitative data regarding the acceptability of use of a vaginal ring inserted once every 4 weeks over the trial period; Percentage of participants with positive response.
Response of 'likely' or 'very likely' to the question: 'If in the future a vaginal ring was available that provided some protection against HIV, and it was similar to the one you used in this trial, how likely would you be to keep it inserted in your vagina every day?'
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12 months per participant
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Human Immunodeficiency Virus Type 1 Drug Resistance Mutations Among Participants Who Acquired HIV-1 Infection.
Time Frame: minimum of 12 months and a maximum of 14 months per participant
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The analysis of HIV-1 drug resistance will be primarily descriptive in nature, and will depend on the pattern of resistance mutations observed in the HIV-1 seroconverters.
The percentage of HIV-1 seroconverters with at least one HIV-1 drug resistant mutation will be presented overall, and by treatment arm, with corresponding 95% CIs.
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minimum of 12 months and a maximum of 14 months per participant
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Collaborators and Investigators
Investigators
- Study Chair: Jared Baeten, MD, PhD, International Clinical Research Center, Department of Global Health, University of Washington
- Study Chair: Thesla Palanee, PhD, Wits Reproductive Health and HIV Institute (WRHI), Research Centre
Publications and helpful links
General Publications
- Browne EN, Brown ER, Palanee-Phillips T, Reddy K, Naidoo L, Jeenarain N, Nair G, Husnik MJ, Singh D, Scheckter R, Soto-Torres L, Baeten JM, van der Straten A; MTN-020/ASPIRE Study Team. Patterns of Adherence to a Dapivirine Vaginal Ring for HIV-1 Prevention Among South African Women in a Phase III Randomized Controlled Trial. J Acquir Immune Defic Syndr. 2022 Aug 1;90(4):418-424. doi: 10.1097/QAI.0000000000002990.
- Leslie J, Kiweewa F, Palanee-Phillips T, Bunge K, Mhlanga F, Kamira B, Baeten J, Katz A, Hillier S, Montgomery E; MTN-020/ASPIRE Study Team. Experiences with simultaneous use of contraception and the vaginal ring for HIV prevention in sub-Saharan Africa. BMC Womens Health. 2021 Apr 23;21(1):175. doi: 10.1186/s12905-021-01321-5.
- Mayo AJ, Browne EN, Montgomery ET, Torjesen K, Palanee-Phillips T, Jeenarain N, Seyama L, Woeber K, Harkoo I, Reddy K, Tembo T, Mutero P, Tauya T, Chitukuta M, Gati Mirembe B, Soto-Torres L, Brown ER, Baeten JM, van der Straten A; MTN-020/ASPIRE study team. Acceptability of the Dapivirine Vaginal Ring for HIV-1 Prevention and Association with Adherence in a Phase III Trial. AIDS Behav. 2021 Aug;25(8):2430-2440. doi: 10.1007/s10461-021-03205-z. Epub 2021 Mar 13.
- Palanee-Phillips T, Brown ER, Szydlo D, Matovu Kiweewa F, Pather A, Harkoo I, Nair G, Soto-Torres L, Hillier SL, Baeten JM; MTN-020/ASPIRE Study Team. Risk of HIV-1 acquisition among South African women using a variety of contraceptive methods in a prospective study. AIDS. 2019 Aug 1;33(10):1619-1622. doi: 10.1097/QAD.0000000000002260.
- Kiweewa FM, Brown E, Mishra A, Nair G, Palanee-Phillips T, Mgodi N, Nakabiito C, Chakhtoura N, Hillier SL, Baeten JM; MTN-020/ASPIRE Study Team. Acquisition of Sexually Transmitted Infections among Women Using a Variety of Contraceptive Options: A prospective Study among High-risk African Women. J Int AIDS Soc. 2019 Feb;22(2):e25257. doi: 10.1002/jia2.25257. Erratum In: J Int AIDS Soc. 2019 Apr;22(4):e25280.
- Riddler SA, Balkus JE, Parikh UM, Mellors JW, Akello C, Dadabhai S, Mhlanga F, Ramjee G, Mayo AJ, Livant E, Heaps AL, O'Rourke C, Baeten JM; MTN-015 and MTN-020/ASPIRE Study Teams. Clinical and Virologic Outcomes Following Initiation of Antiretroviral Therapy Among Seroconverters in the Microbicide Trials Network-020 Phase III Trial of the Dapivirine Vaginal Ring. Clin Infect Dis. 2019 Jul 18;69(3):523-529. doi: 10.1093/cid/ciy909.
- Mensch BS, Richardson BA, Husnik M, Brown ER, Kiweewa FM, Mayo AJ, Baeten JM, Palanee-Phillips T, van der Straten A; MTN-020/ASPIRE study team. Vaginal Ring Use in a Phase 3 Microbicide Trial: A Comparison of Objective Measures and Self-reports of Non-adherence in ASPIRE. AIDS Behav. 2019 Feb;23(2):504-512. doi: 10.1007/s10461-018-2261-8.
- Baeten JM, Palanee-Phillips T, Brown ER, Schwartz K, Soto-Torres LE, Govender V, Mgodi NM, Matovu Kiweewa F, Nair G, Mhlanga F, Siva S, Bekker LG, Jeenarain N, Gaffoor Z, Martinson F, Makanani B, Pather A, Naidoo L, Husnik M, Richardson BA, Parikh UM, Mellors JW, Marzinke MA, Hendrix CW, van der Straten A, Ramjee G, Chirenje ZM, Nakabiito C, Taha TE, Jones J, Mayo A, Scheckter R, Berthiaume J, Livant E, Jacobson C, Ndase P, White R, Patterson K, Germuga D, Galaska B, Bunge K, Singh D, Szydlo DW, Montgomery ET, Mensch BS, Torjesen K, Grossman CI, Chakhtoura N, Nel A, Rosenberg Z, McGowan I, Hillier S; MTN-020-ASPIRE Study Team. Use of a Vaginal Ring Containing Dapivirine for HIV-1 Prevention in Women. N Engl J Med. 2016 Dec 1;375(22):2121-2132. doi: 10.1056/NEJMoa1506110. Epub 2016 Feb 22.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- RNA Virus Infections
- Virus Diseases
- Blood-Borne Infections
- Communicable Diseases
- Sexually Transmitted Diseases, Viral
- Sexually Transmitted Diseases
- Lentivirus Infections
- Retroviridae Infections
- Immunologic Deficiency Syndromes
- Immune System Diseases
- HIV Infections
- Infections
- Anti-Infective Agents
- Antiviral Agents
- Anti-HIV Agents
- Anti-Retroviral Agents
- Dapivirine
Other Study ID Numbers
- MTN-020
- UM1AI068633-06 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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