Evaluating the Safety of and Adherence to a Vaginal Matrix Ring Containing Dapivirine and Oral Emtricitabine/Tenofovir Disoproxil Fumarate in an Adolescent and Young Adult Female Population
Condition: HIV Infections
MeSH terms: HIV Infections
Intervention: Dapivirine vaginal ring; FTC/TDF
Intervention description: Vaginal ring containing 25 mg of dapivirine; Tablet containing 200 mg FTC/300 mg TDF
Intervention MeSH terms: Tenofovir; Emtricitabine; Dapivirine
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 247.0
Sex: Female
Minimum age: 16 Years
Maximum age: 21 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      The purpose of this study is to evaluate the safety of and adherence to a vaginal matrix ring
      (VR) containing dapivirine and oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) in
      adolescent and young adult females.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age 16 through 21 years (inclusive) at Enrollment, verified per site standard
             operating procedures (SOPs).

          -  Able and willing to provide informed consent, and if under the legal age of consent be
             able to provide informed assent and obtain parental or guardian permission/consent, to
             be screened for and to enroll in MTN-034 (as specified in site SOP).

          -  Able and willing to provide adequate locator information, as defined in site SOPs.

          -  Able and willing to comply with all study procedural requirements.

          -  Per participant report at Screening, post-menarche.

          -  HIV-uninfected based on testing performed at Screening and Enrollment (per protocol
             algorithms found in the study protocol).

          -  Per participant report at Screening, history of at least one episode of sexual
             intercourse in participant's lifetime.

          -  Negative pregnancy test at Screening and Enrollment.

          -  Per participant report, use of an effective method of contraception for at least two
             months 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).

               -  Note: Participant must be on the same contraception method for at least the two
                  months prior to Enrollment.

          -  Per participant report at Screening, willing to abstain from inserting anything into
             the vagina for 72 hours prior to each study visit, including receptive intercourse.

               -  Note: In the event the VR has been expelled and requires reinsertion,
                  repositioning the VR is permitted.

               -  Note: Participant use of tampons is permitted at any time during the study.

          -  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 Protocol Safety Review Team (PSRT).

        Exclusion Criteria:

          -  Per participant report at Screening and Enrollment, intends to do any of the following
             during the study participation period:

               -  become pregnant.

               -  access and/or use oral PrEP outside the context of study participation.

               -  relocate away from the study site.

               -  travel away from the study site for a time period that would interfere with
                  product resupply and study participation.

          -  At Screening or Enrollment, has a positive HIV test.

          -  Diagnosed with urinary tract infection (UTI), pelvic inflammatory disease (PID),
             sexually transmitted infection (STI) or reproductive tract infection (RTI) requiring
             treatment per World Health Organization (WHO) guidelines at Screening or Enrollment.

               -  Note: Otherwise eligible participants diagnosed during screening with a UTI, PID
                  or STI/RTI requiring treatment per WHO guidelines - other than asymptomatic
                  bacterial vaginosis (BV) and asymptomatic candidiasis - are offered treatment
                  consistent with WHO recommendations. If treatment is completed and symptoms have
                  resolved within 70 days of obtaining informed assent/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.

          -  At Enrollment, has a clinically apparent Grade 2 or higher pelvic exam finding.

               -  Note: Cervical friability 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 70 days of providing informed assent/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 and polyurethane (ever).

               -  Symptoms suggestive of acute HIV infection at Screening or Enrollment.

               -  Non-therapeutic injection drug use in the 12 months prior to Enrollment.

               -  Use of HIV PEP and/or PrEP within the 3 months prior to Enrollment.

               -  Currently breastfeeding.

               -  Last pregnancy outcome within 8 weeks or less of Enrollment.

               -  Participation in any other research study involving drugs, medical devices,
                  vaginal products or vaccines within 60 days of Enrollment.

               -  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.

          -  Has any of the following laboratory abnormalities at Screening Visit:

               -  Positive for hepatitis B surface antigen (HBsAG).

               -  Hemoglobin Grade 2 or higher.

               -  Calculated creatinine clearance less than 60 mL/min by the Schwartz Equation.

                    -  Note: Otherwise eligible participants with an exclusionary test may be
                       re-tested during the screening process; re-testing procedure details can be
                       found in the MTN-034 Study Specific Procedures (SSP) Manual. If improvement
                       to a non-exclusionary grade or resolution is documented within 70 days of
                       providing informed assent/consent for screening, the participant may be
                       enrolled.

          -  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.