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

NCT03593655 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: MTN-03412066
• Study Type: interventional
• Target: 247
• Locations: 3 countries
• Sites: 4

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.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Grade 2 or Higher Adverse Events (AEs)

  During participants' first year on study (i.e., during first and second product use periods) participants were randomized to use either the dapivirine vaginal ring for 6 months followed by FTC/TDF for 6 months or vice versa. All AEs were reported as per the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events. AEs that were graded as at least Grade 2 (i.e., "moderate" or higher) were classified into the two periods based on reported date of AE onset, with AEs occurring between the participant's randomization date and the date 30 days after their Week 24 visit classified into Period 1, and AEs occurring between their Week 24 visit and the date 30 days after their Week 48 visit classified into Period 2. AEs occurring within 30 days of the Week 24 visit were counted in both periods. This is the number of participant-periods with at least one grade 2 or higher AE by product (combining the two product use periods).

  Study periods 1 and 2

• Number of Participant-Visits With No Product Use

  During the study period where participants were randomized to use FTC/TDF they were assessed for FTC/TDF adherence by dried blood spot (DBS) at monthly visits. Results that were below the lower limit of detection (\< 16.6 fmol/punch) were classified as no use of FTC/TDF during the preceding month, and detectable results (\>= 16.6 fmol/punch) classified as at least some FTC/TDF use. During the study period where participants were randomized to use the dapivirine vaginal ring (VR) they were assessed for ring adherence by residual drug levels in returned VRs. Results that were less than or equal to a rate of 0.9mg dapivirine released per month were classified as no use of the VR during that month, and results greater than 0.9mg dapivirine release per month classified as at least some VR use.

  Study periods 1 and 2

Secondary Outcomes (4)

• Number of Participant-Visits Reporting Acceptability of Study Product

  Study periods 1 and 2

• Number of Participant-Visits With No Product Use

  Study period 3 (Weeks 49-72)

• Number of Participants Selecting Each Study Product

  Study period 3 (Weeks 49-72)

• Percentage of Participants Reporting Preference for Dapivirine VR as Compared to FTC/TDF Oral Tablets

  All three study periods (enrollment, month 12, and month 18 study visits)

Study Arms (2)

Sequence A: Dapivirine vaginal ring + FTC/TDF

EXPERIMENTAL

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.

Device: Dapivirine vaginal ring; Drug: FTC/TDF

Sequence B: FTC/TDF + Dapivirine vaginal ring

EXPERIMENTAL

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.

Device: Dapivirine vaginal ring; Drug: FTC/TDF

Interventions

Dapivirine vaginal ring DEVICE

Vaginal ring containing 25 mg of dapivirine

Sequence A: Dapivirine vaginal ring + FTC/TDF; Sequence B: FTC/TDF + Dapivirine vaginal ring

FTC/TDF DRUG

Tablet containing 200 mg FTC/300 mg TDF

Also known as: Emtricitabine/Tenofovir Disoproxil Fumarate; Truvada

Sequence A: Dapivirine vaginal ring + FTC/TDF; Sequence B: FTC/TDF + Dapivirine vaginal ring

Eligibility Criteria

• Age: 16 Years - 21 Years
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (4)

Wits Reproductive Health and HIV Institute CRS (WRHI CRS)

Johannesburg, Gauteng, 2038, South Africa

Location

Emavundleni CRS

Cape Town, Western Cape, 7750, South Africa

Location

MU-JHU Research Collaboration (MUJHU CARE LTD) CRS

Kampala, Uganda

Location

Spilhaus CRS

Southerton, Harare, Zimbabwe

Location

Related Publications (4)

• Friedland BA, Browne EN, Roberts ST, Ngure K, Nakalega R, Macdonald P, Mpongo CN, Tenza S, Mhlanga N, Szydlo D, Johnson S, McClure T, Nair G, Celum C, Hillier SL, van der Straten A; MTN-034 REACH clinical trial team. Higher Acceptability of the Monthly Dapivirine Ring Versus Daily Oral Pre-Exposure Prophylaxis Among Adolescent Girls and Young Women in Sub-Saharan Africa in the REACH Trial. J Acquir Immune Defic Syndr. 2025 Dec 15;100(5):415-424. doi: 10.1097/QAI.0000000000003756.

  PMID: 40875480 DERIVED

• Shapley-Quinn MK, Tenza S, Jensen D, Tauya T, Mampuru L, Etima J, Kemigisha D, Atujuna M, Soto-Torres L, Johnson S, Mpongo N, Mhlanga N, Ngure K, van der Straten A. Adolescent Girls and Young Women Overcoming Adherence Challenges with Vaginal and Oral PrEP Use: A Longitudinal Qualitative Study from a Crossover Trial in South Africa, Uganda, and Zimbabwe. AIDS Behav. 2024 Dec;28(12):4209-4223. doi: 10.1007/s10461-024-04503-y. Epub 2024 Sep 30.

  PMID: 39343865 DERIVED

• Nair G, Celum C, Szydlo D, Brown ER, Akello CA, Nakalega R, Macdonald P, Milan G, Palanee-Phillips T, Reddy K, Tahuringana E, Muhlanga F, Nakabiito C, Bekker LG, Siziba B, Hillier SL, Baeten JM, Garcia M, Johnson S, McClure T, Levy L, Livant E, Jacobson C, Soto-Torres L, van der Straten A, Hosek S, Rooney JF, Steytler J, Bunge K, Parikh U, Hendrix C, Anderson P, Ngure K; REACH Protocol Team. Adherence, safety, and choice of the monthly dapivirine vaginal ring or oral emtricitabine plus tenofovir disoproxil fumarate for HIV pre-exposure prophylaxis among African adolescent girls and young women: a randomised, open-label, crossover trial. Lancet HIV. 2023 Dec;10(12):e779-e789. doi: 10.1016/S2352-3018(23)00227-8. Epub 2023 Oct 25.

  PMID: 37898146 DERIVED

• Young AM, Mancuso N, Atujuna M, Tenza S, Chitukuta M, Kemigisha D, Ngure K, van der Straten A, Garcia M, Szydlo D, Soto-Torres L, Roberts ST. Adolescent Girls and Young Women's Experiences with Disclosing Oral PrEP or Dapivirine Vaginal Ring Use: a Multi-Country Qualitative Analysis. AIDS Behav. 2023 Dec;27(12):3941-3951. doi: 10.1007/s10461-023-04109-w. Epub 2023 Jul 1.

  PMID: 37392268 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

Emtricitabine; Tenofovir; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Drug Combinations; Pharmaceutical Preparations

Results Point of Contact

• Title: Gonasagrie Nair
• Organization: Stellenbosch University, Centre for Medical Ethics and Law

gnair@sun.ac.za

27-21-938-7050

Study Officials

• Gonasagrie Nair, MBChB, MPH

  Emavundleni Research Centre

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2018
• First Posted: July 20, 2018
• Study Start: January 14, 2019
• Primary Completion: September 9, 2021
• Study Completion: September 9, 2021
• Last Updated: June 22, 2023
• Results First Posted: February 3, 2023

Record last verified: 2023-01

Locations

ZI (1); ZA (2); UG (1)