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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

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ClinicalTrials.gov Identifier: NCT03593655
Recruitment Status : Active, not recruiting
First Posted : July 20, 2018
Last Update Posted : September 14, 2020
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Tracking Information
First Submitted Date  ICMJE July 10, 2018
First Posted Date  ICMJE July 20, 2018
Last Update Posted Date September 14, 2020
Actual Study Start Date  ICMJE January 14, 2019
Estimated Primary Completion Date October 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 10, 2018)
  • Frequency of Grade 2 or higher adverse events (AEs) [ Time Frame: Measured through Week 24 ]
    As defined by the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017 and/or Addendum 1 (Female Genital Grading Table for Use in Microbicide Studies [Dated November 2007])
  • Measurement of detectable drug levels in blood [ Time Frame: Measured through Week 24 ]
    Based on laboratory evaluations
  • Measurement of residual drug levels in returned VRs [ Time Frame: Measured through Week 24 ]
    Based on laboratory evaluations
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 10, 2018)
  • Percentage of participants reporting acceptability of study product [ Time Frame: Measured through Week 24 ]
    Based on participant report
  • Measurement of detectable drug levels in blood [ Time Frame: Measured through Week 72 ]
    Based on laboratory evaluations
  • Measurement of residual drug levels in returned VRs [ Time Frame: Measured through Week 72 ]
    Based on laboratory evaluations
  • Percentage of participants selecting dapivirine VR as compared to FTC/TDF oral tablets [ Time Frame: Measured through Week 72 ]
    Assessed by participant product selection during third product use period
  • Percentage of participants reporting preference for dapivirine VR as compared to FTC/TDF oral tablets [ Time Frame: Measured through Week 72 ]
    Assessed by participant report of product preference
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE HIV Infections
Intervention  ICMJE
  • Device: Dapivirine vaginal ring
    Vaginal ring containing 25 mg of dapivirine
  • Drug: FTC/TDF
    Tablet containing 200 mg FTC/300 mg TDF
    Other Name: Emtricitabine/Tenofovir Disoproxil Fumarate; Truvada
Study Arms  ICMJE
  • Experimental: Sequence A: Dapivirine vaginal ring + FTC/TDF
    Participants will receive one 25 mg dapivirine vaginal ring inserted vaginally each month for 24 weeks, followed by one FTC/TDF oral tablet taken by mouth daily for 24 weeks, followed by participant's choice of either or neither study product for 24 weeks.
    Interventions:
    • Device: Dapivirine vaginal ring
    • Drug: FTC/TDF
  • Experimental: Sequence B: FTC/TDF + Dapivirine vaginal ring
    Participants will receive one FTC/TDF oral tablet taken by mouth daily for 24 weeks, followed by one 25 mg dapivirine vaginal ring inserted vaginally each month for 24 weeks, followed by participant's choice of either or neither study product for 24 weeks.
    Interventions:
    • Device: Dapivirine vaginal ring
    • Drug: FTC/TDF
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: September 11, 2020)
247
Original Estimated Enrollment  ICMJE
 (submitted: July 10, 2018)
300
Estimated Study Completion Date  ICMJE October 31, 2021
Estimated Primary Completion Date October 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Gender Based Eligibility: Yes
Ages  ICMJE 16 Years to 21 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE South Africa,   Uganda,   Zimbabwe
Removed Location Countries Kenya
 
Administrative Information
NCT Number  ICMJE NCT03593655
Other Study ID Numbers  ICMJE MTN-034
12066 ( Registry Identifier: DAIDS-ES Registry Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Institute of Allergy and Infectious Diseases (NIAID)
Study Sponsor  ICMJE National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Gonasagrie Nair, MBChB, MPH Emavundleni Research Centre
PRS Account National Institute of Allergy and Infectious Diseases (NIAID)
Verification Date September 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP