Phase 3 Safety and Effectiveness Trial of Dapivirine Vaginal Ring for Prevention of HIV-1 in Women (ASPIRE)

This study has been completed.
Sponsor:
Collaborator:
National Institutes of Health (NIH)
Information provided by (Responsible Party):
International Partnership for Microbicides, Inc.
ClinicalTrials.gov Identifier:
NCT01617096
First received: June 8, 2012
Last updated: September 9, 2015
Last verified: September 2015
  Purpose
This is a double-blind, randomised, placebo-controlled study to assess the safety and efficacy of a silicone elastomer vaginal matrix ring.

Condition Intervention Phase
HIV Infections
Drug: Dapivirine
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: 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

Resource links provided by NLM:


Further study details as provided by International Partnership for Microbicides, Inc.:

Primary Outcome Measures:
  • 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: 24 months ] [ Designated as safety issue: No ]
    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.

  • Safety as determined by Grade 2 AEs judged to be product related; Grade 3 and 4 AEs; and all serious AEs reported (based on DAIDS grading) [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]

Enrollment: 3540
Study Start Date: August 2012
Study Completion Date: August 2015
Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dapivirine
Vaginal ring containing 25mg dapivirine
Drug: Dapivirine
Dosage form: vaginal ring Dosage: 25mg Frequency: monthly Duration: 12 months
Placebo Comparator: Placebo
Vaginal ring containing no drug substance
Drug: Placebo
Vaginal ring containing no drug substance

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01617096

Locations
Malawi
College of Medicine - Johns Hopkins University Research Project
Blantyre, Malawi
UNC Project
Lilongwe, Malawi
South Africa
CAPRISA, eThekwini Clinical Research Site
Durban, KwaZulu-Natal, South Africa
Desomond Tutu HIV Center
Cape Town, South Africa
Wits Reproductive Health and HIV Institute
Johannesburg, South Africa
Uganda
MU-JHU Care LTD, MU-JHU Research Collaboration
Kampala, Uganda
Zimbabwe
UZ-Obstetrics & Gynecology Research Clinic at Spillhaus
Belgravia, Harare, Zimbabwe
Sponsors and Collaborators
International Partnership for Microbicides, Inc.
National Institutes of Health (NIH)
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
  More Information

Responsible Party: International Partnership for Microbicides, Inc.
ClinicalTrials.gov Identifier: NCT01617096     History of Changes
Other Study ID Numbers: MTN-020 
Study First Received: June 8, 2012
Last Updated: September 9, 2015
Health Authority: United States: Food and Drug Administration
South Africa: Medicines Control Council
Uganda: National Drug Authority

Keywords provided by International Partnership for Microbicides, Inc.:
HIV Infections
Anti-HIV agents
HIV-1

Additional relevant MeSH terms:
Infection
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases

ClinicalTrials.gov processed this record on July 21, 2016