Clinical trial NCT03593655: 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
Official title: A Phase 2a Crossover Trial 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2018-07-20
Enrollment: 247
Sex: FEMALE
Minimum age (years): 16
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

Brief 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.

Detailed description: This study will 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.

The study will enroll healthy, HIV-uninfected adolescent and young adult females between 16 and 21 years of age. Participants will be randomized to one of two sequences of one VR containing 25 mg of dapivirine to be inserted monthly for 24 weeks and one 200 mg FTC/300 mg TDF oral tablet taken daily for 24 weeks. After completing the randomized sequence of two study product use periods, participants will then select between the two study products to use in the final 24 weeks of the trial. Participants will be able to choose either or neither study product during the third product use period. The study includes approximately 76 weeks of follow-up per participant.

Participants will attend monthly study visits, which may include behavioral assessments/counseling; physical and pelvic examinations; and blood, urine, and pelvic sample collection.

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.

Primary outcomes:
measure: Number of Participants With Grade 2 or Higher Adverse Events (AEs)
timeFrame: Study periods 1 and 2
measure: Number of Participant-Visits With No Product Use
timeFrame: Study periods 1 and 2
Secondary outcomes:
measure: Number of Participant-Visits Reporting Acceptability of Study Product
timeFrame: Study periods 1 and 2
measure: Number of Participant-Visits With No Product Use
timeFrame: Study period 3 (Weeks 49-72)
measure: Number of Participants Selecting Each Study Product
timeFrame: Study period 3 (Weeks 49-72)
measure: Percentage of Participants Reporting Preference for Dapivirine VR as Compared to FTC/TDF Oral Tablets
timeFrame: All three study periods (enrollment, month 12, and month 18 study visits)
Other outcomes:
Locations:
city: Johannesburg
country: South Africa
facility: Wits Reproductive Health and HIV Institute CRS (WRHI CRS)
state: Gauteng
city: Cape Town
country: South Africa
facility: Emavundleni CRS
state: Western Cape
city: Kampala
country: Uganda
facility: MU-JHU Research Collaboration (MUJHU CARE LTD) CRS
city: Southerton
country: Zimbabwe
facility: Spilhaus CRS
state: Harare
Study officials:
affiliation: Emavundleni Research Centre
name: Gonasagrie Nair, MBChB, MPH
role: STUDY_CHAIR
References: