Study of Dapivirine Vaginal Ring (VR) in Adolescents
Condition: Human Immunodeficiency Virus
MeSH terms: Acquired Immunodeficiency Syndrome; HIV Infections; Immunologic Deficiency Syndromes
Intervention: placebo ring; dapivirine ring
Intervention description: intravaginal ring silicone elastomer intravaginal ring containing no drug product; intravaginal ring silicone elastomer intravaginal ring containing 25 mg dapivirine
Intervention MeSH terms: Dapivirine
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 96.0
Sex: Female
Minimum age: 15 Years
Maximum age: 17 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Human Immunodeficiency Virus

Summary:

      To assess the safety of dapivirine (25 mg) administered via a silicone vaginal ring in
      HIV-uninfected adolescent females, when inserted once every 4 weeks during 24-week of study
      product use.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age 15 through 17 years (inclusive) at Enrollment, verified per site SOPs

          2. Able and willing to provide written informed assent/consent and able to obtain written
             parental or guardian permission (as specified in site SOP) to be screened for and to
             enroll in MTN-023/IPM 030

          3. Able and willing to provide adequate locator information, as defined in site SOPs

          4. Able to communicate in spoken and written English

          5. Able and willing to comply with all study procedural requirements

          6. Per participant report at Screening and Enrollment, willing to abstain from inserting
             anything into the vagina for 72 hours prior to each follow-up visit, including
             abstaining from penile-vaginal intercourse. Note: In the event the vaginal ring has
             been expelled and requires reinsertion, repositioning the vaginal ring is permitted

          7. In general good health as determined by the Investigator of Record (IoR)/designee at
             Screening and Enrollment

          8. Assessment of onset and progression of puberty, as measured by Tanner stage 4 or 5 at
             Screening, per participant report and/or clinician assessment

          9. HIV-uninfected based on testing performed at Screening and Enrollment (per protocol
             algorithm in Appendix II)

         10. Per participant report at Screening, history of sexual intercourse (at least one
             episode in participant's lifetime)

         11. Per participant report at Screening and Enrollment, agrees to use condoms for sexual
             intercourse

         12. Negative pregnancy test at Screening and Enrollment

         13. Per participant report, using an effective method of contraception for at least 30
             days (inclusive) prior to Enrollment, and intending to continue use of an effective
             method for the duration of study participation; effective methods include:

               -  hormonal methods (except contraceptive ring)

               -  intrauterine device (IUD)

               -  sterilization (of participant, as defined in site SOPs)

         14. At Screening and Enrollment, participant states a willingness to refrain from
             inserting the following vaginal products and/or objects into the vagina; spermicides,
             diaphragms, contraceptive vaginal rings, menstrual cups, cervical caps (or any other
             vaginal barrier method), douches, lubricants, for the 5 days prior to Enrollment
             throughout the duration of study participation. Note: Neither the use of tampons or
             sex toys, nor participant engagement in coitus is restricted.

         15. 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, unless approved by the PSRT

        Exclusion Criteria:

          1. Per participant report at Screening, intends to do any of the following during the
             study participation period:

               1. become pregnant

               2. relocate away from the study site

               3. travel away from the study site for more than 4 consecutive weeks

          2. Diagnosed with a urinary tract infection (UTI) and/or reproductive tract infection
             (RTI) at Screening and/or Enrollment. Note: Otherwise eligible participants diagnosed
             with UTI during Screening will be offered treatment and may be enrolled after
             completing treatment and all symptoms have resolved. If treatment is completed and
             symptoms have resolved within 56 days of obtaining informed consent for Screening, the
             participant may be enrolled.

          3. Diagnosed with pelvic inflammatory disease and/or an sexually transmitted infection
             (STI) requiring treatment per current Centers for Disease Control and Prevention (CDC)
             guidelines within 60 days of Enrollment (inclusive)

          4. At Enrollment, has a clinically apparent Grade 2 or higher pelvic exam finding
             (observed by study staff)** 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 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 56 days of providing informed consent for
             screening, the participant may be enrolled.

          5. Participant report and/or clinical evidence of any of the following:

               1. Known adverse reaction to any of the study products (ever)

               2. Known HIV-infected partner

               3. Non-therapeutic injection drug use in the 12 months prior to Screening

               4. The use of HIV Post-exposure prophylaxis (PEP) and/or Pre-exposure prophylaxis
                  (PrEP) within the 6 months prior to Enrollment

               5. Currently breastfeeding

               6. Last pregnancy outcome within 90 days or less of Screening

               7. Participation in any other research study involving drugs, medical devices,
                  vaginal products, or vaccines, within 60 days of Screening

               8. Participant report of 3 or more penile-vaginal sexual partners in the month prior
                  to Screening

               9. At Enrollment, as determined by the IoR/designee, has any significant
                  uncontrolled active or chronic cardiovascular, renal, liver, hematologic,
                  neurologic, gastrointestinal, psychiatric, endocrine, respiratory, immunologic
                  disorder or infectious disease

          6. Has any of the following Grade 1 or higher* laboratory abnormalities at Screening
             Visit:

               1. Aspartate aminotransferase (AST) or alanine transaminase (ALT)

               2. Creatinine

               3. Hemoglobin

               4. Platelet count Note: Otherwise eligible participants with an exclusionary test
                  may be re-tested during the screening process. Please see the MTN-023/IPM 030 SSP
                  for additional details.

          7. Has any other condition that, in the opinion of the IoR/designee, would preclude
             informed assent/consent, make study participation unsafe, complicate interpretation of
             study outcome data, or otherwise interfere with achieving the study objectives

               -  Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse
                  Events Version 1.0, December, 2004 (Clarification dated August 2009) **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)