Phase 3 Safety and Effectiveness Trial of Dapivirine Vaginal Ring for Prevention of HIV-1 in Women
Condition: HIV Infections
MeSH terms: Infections; HIV Infections
Intervention: Dapivirine Vaginal Ring; Placebo Ring
Intervention description: Dosage form: vaginal ring Dosage: 25mg Frequency: monthly Duration: 12 months; Vaginal ring containing no drug substance
Intervention MeSH terms: Dapivirine
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 2629.0
Sex: Female
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: HIV Infections; Anti-HIV agents; HIV-1

Summary:

      This is a double-blind, randomised, placebo-controlled study to assess the safety and
      efficacy of a silicone elastomer vaginal matrix ring.
    

Eligibility 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