Trial to Assess Acceptability and Safety of Two Placebo Intravaginal Rings

NCT06163274 | Terminated Early Phase 1

• 1 other identifier: STUDY23070172
• Study Type: interventional
• Target: 93
• Locations: 3 countries
• Sites: 5

Brief Summary

This research study is being conducted to find out how easy, comfortable, and safe intravaginal rings are for women to use. The two rings used in this study do not dispense any medications, are the same size, but differ in their flexibility and hardness. This study will enroll approximately 100 HIV-negative persons, aged18-45 years, and assigned female sex at birth from sites in the United States, South Africa, and Zimbabwe. Participants will be randomly assigned to use (self-insert) Ring A for 4 weeks and then Ring B for 4 weeks or Ring B first followed by Ring A. There will be a 1-3-week rest period between using the two different rings. The study involves answering questions, undergoing pelvic examinations, and collecting blood and vaginal fluid samples over a total of 7 in-person visits and 2 telephone calls over approximately 9-11 weeks. In addition, both participants and approximately 30 of their sexual partners will be asked to take part in in-depth interviews to further assess acceptability, attitudes, and experiences with ring use to gauge interest in the future use of intravaginal rings as a HIV prevention option.

Conditions

Safety; Acceptability

Keywords

Vagina; Placebo; Intravaginal Ring

Outcome Measures

Primary Outcomes (2)

• Number of Participants Preferring to Use Placebo Intravaginal Ring A versus Ring B

  Number of participants that report a preference to use placebo intravaginal Ring A versus Ring B

  Through study completion, approximately 11 weeks

• Mean Satisfaction with Placebo Intravaginal Ring Use

  Satisfaction will be assessed using a 10-point Likert scale with 0 being the least satisfied and 10 being the most satisfied

  Through study completion, approximately 11 weeks

Secondary Outcomes (1)

• Number of Participants with Genitourinary Grade 2 or Higher Adverse Events

  Through study completion, approximately 11 weeks

Other Outcomes (1)

• Mean Change in Nugent Score

  Through study completion, approximately 11 weeks

Study Arms (2)

Sequence: Placebo Intravaginal Ring A followed by Placebo Intravaginal Ring B

EXPERIMENTAL

Placebo Intravaginal Ring A will be inserted and used for 28 days, Ring A will be removed and followed by no intravaginal ring use for 7-21 days. Then Placebo Intravaginal Ring B will be inserted and used for 28 days.

Device: Placebo Intravaginal Ring A; Device: Placebo Intravaginal Ring B

Sequence: Placebo Intravaginal Ring B followed by Placebo Intravaginal Ring A

EXPERIMENTAL

Placebo Intravaginal Ring B will be inserted and used for 28 days, Ring B will be removed and followed by no intravaginal ring use for 7-21 days. Then Placebo Intravaginal Ring A will be inserted and used for 28 days.

Device: Placebo Intravaginal Ring A; Device: Placebo Intravaginal Ring B

Interventions

Placebo Intravaginal Ring A DEVICE

Placebo Intravaginal Ring A consists of a flexible lavender silicone scaffold, with an outer diameter of 55 mm and a durometer value of 40A (Shore A hardness scale). The ring holds two blank grey cassettes.

Sequence: Placebo Intravaginal Ring A followed by Placebo Intravaginal Ring B; Sequence: Placebo Intravaginal Ring B followed by Placebo Intravaginal Ring A

Placebo Intravaginal Ring B DEVICE

Placebo Intravaginal Ring B consists of a flexible lavender silicone scaffold, with an outer diameter of 55 mm and a durometer value of 50A (Shore A hardness scale). The ring holds two blank grey cassettes.

Sequence: Placebo Intravaginal Ring A followed by Placebo Intravaginal Ring B; Sequence: Placebo Intravaginal Ring B followed by Placebo Intravaginal Ring A

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Assigned female sex at birth.
• Able and willing to provide written informed consent to be screened for and enrolled in MATRIX-003 in one of the study languages.
• Able and willing to provide adequate contact/locator information.
• Able and willing to comply with all protocol requirements, including:
• Abstaining from other intravaginal products or practices for the duration of the study.
• Abstaining from penetrative vaginal intercourse (i.e., oral-, digital-, penile-penetration) for the first 14 days of each product use period.
• Refraining from participation in other research studies involving drugs, medical devices, vaginal products, or vaccines starting 2 weeks before the Screening Visit and for the duration of the study, or in observational or qualitative studies for the duration of the study, unless approved by the Protocol Safety Review Team.
• Reliable access to a private phone for scheduled phone contacts.
• HIV-uninfected based on testing performed at Screening and Enrollment.
• Per participant report, must be either not currently sexually active or in a mutually monogamous relationship with only one partner who is not known to be HIV positive or to currently have a sexually transmitted infection.
• Negative urine pregnancy test at Screening and Enrollment.
• Participants over the age of 21 (inclusive) must have documentation of a Grade 0 Pap smear within the past 3 years prior to Enrollment, or a Grade 1 Pap smear at Screening with no treatment required.
• Protected from pregnancy starting at least 2 weeks before Screening and continuing for the duration of study participation by an effective contraceptive method; effective methods include:
• Hormonal methods except vaginal rings
• Copper intrauterine device

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.
• Breastfeed.
• Relocate away from the study site.
• Travel away from the study site for a time period that would interfere with product resupply and/or study participation.
• Positive HIV test at Screening or Enrollment.
• Positive test for Trichomonas vaginalis, Neisseria gonorrhea, Chlamydia trachomatis, or Treponema pallidum (Syphilis) at Screening and (per participant report) treated for potential sexually transmitted infection within past 12 months.
• Diagnosed with urinary tract infection, pelvic inflammatory disease, or reproductive tract infection requiring treatment at Enrollment.
• Note: Otherwise eligible participants diagnosed during screening with a urinary tract infection, symptomatic yeast infection or symptomatic bacterial vaginosis infection are offered treatment. If treatment is completed and symptoms have resolved within 45 days of obtaining informed consent for screening, the participant may be enrolled.
• Clinically apparent Grade 2 or higher pelvic exam finding at Enrollment.
• Participant report and/or clinical evidence of any of the following:
• Known adverse reaction to silicone (ever).
• Use of diaphragm, NuvaRing, or spermicide for contraception starting 2 weeks prior to Screening through Enrollment.
• Use of any of the following in the past 12 months: stimulants (cocaine \[including crack\], methamphetamine, or non-physician prescribed pharmaceutical-grade stimulants), or inhaled nitrates, or illicit injection drug use of any kind.
• Prior use of post-exposure prophylaxis or oral pre-exposure prophylaxis (including Emtricitabine/tenofovir) in the past 4 weeks or any prior use of long-acting systemic pre-exposure prophylaxis (including cabotegravir or islatravir).

Sponsors & Collaborators

• University of Pittsburgh: lead
• United States Agency for International Development (USAID): collaborator
• Oak Crest Institute of Science: collaborator

Study Sites (5)

Magee-Womens Hospital of UPMC

Pittsburgh, Pennsylvania, 15213, United States

Location

Wits Reproductive Health and HIV Institute

Hillbrow, Johannesburg, 2038, South Africa

Location

Centre for the AIDS Programme of Research in South Africa - Vululindlela

Pietermaritzburg, KwaZulu-Natal, 3291, South Africa

Location

The Aurum Institue - Tembisa #4

Tembisa, 1632, South Africa

Location

Harare Health and Research Consortium

Chitungwiza, Zimbabwe

Location

Related Publications (4)

• Palanee-Phillips T, Baum MM, Moss JA, Clark MR, Nuttall J, Romano JW. Drug-releasing vaginal rings for HIV/STI and pregnancy prevention: a review of recent advances and clinical applications. Expert Opin Drug Deliv. 2022 Jan;19(1):47-58. doi: 10.1080/17425247.2022.2020242. Epub 2022 Jan 7.

  PMID: 34958283 BACKGROUND

• Ridgeway K, Montgomery ET, Smith K, Torjesen K, van der Straten A, Achilles SL, Griffin JB. Vaginal ring acceptability: A systematic review and meta-analysis of vaginal ring experiences from around the world. Contraception. 2022 Feb;106:16-33. doi: 10.1016/j.contraception.2021.10.001. Epub 2021 Oct 10.

  PMID: 34644609 BACKGROUND

• Stoner MCD, Browne EN, Gundacker HM, Hawley I, Chen BA, Hoesley C, Scheckter R, Piper J, Singh D, Song M, Liu A, van der Straten A. Acceptability of an extended duration vaginal ring for HIV prevention and interest in a multi-purpose ring. PLoS One. 2022 Feb 22;17(2):e0263664. doi: 10.1371/journal.pone.0263664. eCollection 2022.

  PMID: 35192655 BACKGROUND

• Minnis AM, Etima J, Musara P, Browne EN, Mutero P, Kemigisha D, Mgodi NM, Nakabiito C, Shapley-Quinn MK, Stoner MCD, Hartmann M, Macagna N, Piper J, van der Straten A. Couples' Preferences for "2 in 1" Multipurpose Prevention Technologies to Prevent Both HIV and Pregnancy: Results of a Discrete Choice Experiment in Uganda and Zimbabwe. AIDS Behav. 2022 Dec;26(12):3848-3861. doi: 10.1007/s10461-022-03713-6.

  PMID: 35674885 BACKGROUND

Study Officials

• Catherine A Chappell, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The participants, care providers, and investigators may be able to tell the difference in the hardness/flexibility of the two rings after handling them.
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Participants will randomized to sequence of using 2 placebo intravaginal rings; Ring A followed by Ring B or Ring B followed by Ring A

Study Record Dates

• First Submitted: November 30, 2023
• First Posted: December 8, 2023
• Study Start: February 28, 2024
• Primary Completion: January 24, 2025
• Study Completion: January 24, 2025
• Last Updated: March 3, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

ZA (3); ZI (1); US (1)