Safety and Drug Detection Study of Dapivirine Vaginal Ring and Oral TRUVADA® in Breastfeeding Mother-Infant Pairs
Condition: HIV Infections
MeSH terms: HIV Infections
Intervention: Dapivirine (DPV) Vaginal Ring (VR)-004; Truvada Tablet
Intervention description: Vaginal ring containing 25 mg of DPV; Oral tablet containing 200 mg emtricitabine (FTC)/300 mg tenofovir disoproxil fumarate (TDF)
Intervention MeSH terms: Tenofovir; Emtricitabine; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Dapivirine
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 394.0
Sex: All
Minimum age: 6 Weeks
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      The purpose of this study is to evaluate the safety and drug detection of the dapivirine
      vaginal ring and oral Truvada in breastfeeding mother-infant pairs.
    

Eligibility criteria:

        Inclusion Criteria:

        Inclusion Criteria - Mother

        Participant mothers must meet all the following criteria to be eligible for inclusion in
        the study:

          -  Age 18 years or older at Screening, as verified per site Standard Operating Procedures
             (SOPs).

          -  At Enrollment, between 6 to 12 weeks postpartum (verified by birth records and/or
             similar supportive documentation and defined as between 42 - 84 days after delivery,
             inclusive).

          -  By participant report at Screening and Enrollment, currently exclusively breastfeeding
             one infant and willing and able to continue exclusively breastfeeding that infant for
             the duration of their participation in the study.

               -  Note: Exclusive breastfeeding will be defined as infant nutrition solely from
                  breast milk, as determined by 7-day recall breastfeeding history. For the
                  purposes of MTN-043, "breastfeeding" refers to all human milk feeding situations
                  when an infant is fed with participant's own human milk whether the milk is
                  received directly from the breast or as expressed milk.

          -  Consistently using an effective method of contraception per participant report at
             Enrollment, and intending to continue use of an effective method for the duration of
             study participation. Effective methods include contraceptive implants, intrauterine
             device, injectable progestin, oral contraceptive pills, and surgical sterilization.

          -  Able and willing to comply with all study requirements and complete all study
             procedures.

          -  Able and willing to provide the following:

               -  Written informed consent to be screened for and to take part in the study.

               -  Written informed consent for the breastfed infant to be screened for and take
                  part in the study.

          -  Intention to stay within study catchment area for study duration and willingness to
             give adequate locator information, as defined in site SOPs.

          -  At Screening and Enrollment, HIV-uninfected based on HIV testing performed by study
             staff (per algorithm in the study protocol).

          -  At Screening and Enrollment, willing to be randomized at time of enrollment to either
             of the study products, and to continue study product use for at least 12 weeks.

        Inclusion Criteria - Infant

        Each mother eligible for MTN-043 will be asked to provide written informed consent for
        herself and her infant to participate in the study if the infant meets the following
        criteria:

          -  At Screening and Enrollment, infant is exclusively breastfed.

               -  Note: Exclusive breastfeeding will be defined as infant nutrition solely from
                  breast milk, as determined by 7-day recall breastfeeding history. For the
                  purposes of MTN-043, "breastfeeding" refers to all human milk feeding situations
                  when an infant is fed with participant's own human milk whether the milk is
                  received directly from the breast or as expressed milk.

          -  At Screening and Enrollment, the infant is generally healthy, according to the
             judgment of the investigator of record (IoR)/designee.

          -  At Enrollment, the infant is between the ages of 6 and 12 weeks postpartum (verified
             by birth records and/or similar supportive documentation with age defined as between
             42 - 84 days after delivery, inclusive).

        Exclusion Criteria:

        Exclusion Criteria - Mother

        Mothers who meet any of the following criteria will be excluded from the study:

          -  At Screening or Enrollment, breastfeeding infant ineligible for enrollment in the
             study.

          -  At Screening or Enrollment, participant reports any of the following:

               -  Known adverse reaction to any of the study products (ever).

               -  Known adverse reaction to latex and polyurethane (ever).

               -  Post-exposure prophylaxis (PEP) for HIV exposure within 6 months prior to
                  Enrollment.

               -  Use of vaginal medications(s) or other vaginal products within five days prior to
                  Enrollment.

               -  Non-therapeutic injection drug use in the 12 months prior to Enrollment.

               -  History of exposure to any investigational drug(s) during pregnancy, including
                  participation in MTN-042.

          -  At Screening or Enrollment, has a positive HIV test.

          -  At Screening or Enrollment, Grade 2 or higher breast or genitourinary findings.

          -  At Screening or Enrollment, has a positive urinary pregnancy test.

          -  At Screening, has any of the following laboratory abnormalities:

               -  Positive for hepatitis B surface antigen (HBsAg).

               -  Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≥ Grade 2.

               -  Creatinine ≥ Grade 1.

               -  Estimated creatinine clearance ≥ Grade 2 (Cockcroft Gault formula).

          -  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.

               -  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 vulvovaginal candidiasis - are offered
                  treatment consistent with WHO recommendations and may be enrolled after
                  completing treatment if all symptoms have resolved. If treatment is completed and
                  symptoms have resolved prior to obtaining informed consent for Screening, the
                  participant may be enrolled. Genital warts requiring treatment also must be
                  treated prior to enrollment. Genital warts requiring treatment are defined as
                  those that cause undue burden or discomfort to the participant, including bulky
                  size, unacceptable appearance, or physical discomfort.

          -  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.

          -  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.

          -  At Enrollment, participant reports any of the following:

               -  Participation in any research study involving drugs, vaccines, or medical devices
                  30 days or less prior to enrollment.

               -  Currently participating in other research studies involving drugs, vaccines, or
                  medical devices.

               -  Expected to participate in other research studies involving drugs, vaccines, or
                  medical devices during study participation.

        Exclusion Criteria - Infants

          -  Has any condition that, in the opinion of the IoR/designee, would preclude
             eligibility, make study participation unsafe, complicate interpretation of study
             outcome data, or otherwise interfere with achieving the study objectives.

               -  Note: Examples of exclusionary infant conditions include clinical evidence of
                  stunting or illness.

          -  At Enrollment, according to the report of the mother, any of the following apply for
             the infant:

               -  Infants with birth weight less than 2000g.

               -  Participation in any research study involving drugs, vaccines, or medical devices
                  since birth.

               -  Currently participating in other research studies involving drugs, vaccines, or
                  medical devices.

               -  Expected to participate in other research studies involving drugs, vaccines, or
                  medical devices for the duration of study participation.