Placebo Intravaginal Rings for Acceptability and Safety

(MATRIX-003 Trial)

No longer recruiting at 4 trial locations

Overseen By Jamie Haggerty

Age: 18 - 65

Sex: Female

Trial Phase: Phase < 1

Sponsor: University of Pittsburgh

Must not be taking: Stimulants, Inhaled nitrates, Antibiotics, others

Disqualifiers: HIV, STIs, Pregnancy, Hysterectomy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 9

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the comfort and safety of intravaginal rings for women. It involves two types of rings, Placebo Intravaginal Ring A and Placebo Intravaginal Ring B, which do not release medication but differ in flexibility and hardness. Participants will use each ring for four weeks with a break in between, and the study will assess ease of use and acceptability. The trial is suitable for HIV-negative women who are not currently pregnant, have not had certain infections in the past year, and can commit to the study's requirements. As an Early Phase 1 trial, this research aims to understand how these rings function in people, offering participants a chance to contribute to groundbreaking research.

Do I need to stop taking my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot use antibiotics, steroids, or antifungal therapies within 14 days of enrollment. It's best to discuss your specific medications with the study team.

What prior data suggests that these intravaginal rings are safe for use?

In a previous study, researchers examined the safety of intravaginal rings, which are generally considered safe. Since the rings in this study do not release medication, potential risks are even lower.

The study is in an early phase, focusing mainly on safety and comfort. This stage usually involves fewer participants, allowing researchers to closely monitor any side effects. However, since these rings are only placebos (fake rings with no active medicine), they are expected to be well-tolerated.

Participants will report on their comfort and any problems experienced while using the rings. Past research on similar rings has shown that most people do not encounter significant issues. The most common side effects might include slight discomfort or irritation, but with placebo rings, these effects are less likely.

Overall, the placebo rings are expected to be safe and not cause significant side effects.

Why are researchers excited about this trial?

Researchers are excited about these placebo intravaginal rings because they are exploring the acceptability and safety of a new delivery method for potential future treatments. Unlike existing treatments for conditions like vaginal infections or hormonal imbalances, which often come in the form of creams, pills, or hormonal rings, these placebo rings help to study how comfortable and easy the rings are to use without any active medication. The unique aspect is the focus on user experience and safety, which could pave the way for more user-friendly options in the future. Ultimately, understanding the acceptability of such delivery methods can help tailor more effective and comfortable treatments down the line.

What evidence suggests that these intravaginal rings are easy, comfortable, and safe to use?

This study aims to assess the comfort and safety of intravaginal rings. The rings in this trial contain no medication; they test different levels of flexibility and firmness. Participants will use either Placebo Intravaginal Ring A followed by Placebo Intravaginal Ring B, or vice versa, to evaluate comfort and safety. While no data exists on these specific rings, as they don't deliver medication, previous research has shown that intravaginal rings can effectively deliver treatments, such as for HIV prevention. The goal is to understand how these rings feel and function in everyday use. Participants will provide insights that could enhance future ring designs for delivering actual treatments.

Who Is on the Research Team?

Catherine A Chappell, MD

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

This trial is for HIV-negative women aged 18-45, who are not pregnant or planning to become so, and are either not sexually active or in a monogamous relationship. They must be willing to avoid other vaginal products and abstain from sex for the first two weeks of each ring use period.

Inclusion Criteria

Able and willing to provide adequate contact/locator information

Abstaining from penetrative vaginal intercourse for the first 14 days of each product use period

Negative urine pregnancy test at Screening and Enrollment

Exclusion Criteria

I do not plan to become pregnant, breastfeed, move away, or travel in a way that would affect my participation in the study.

I tested positive for an STI and have been treated for it in the past year.

My pelvic exam showed a noticeable issue of Grade 2 or higher.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment Phase 1

Participants use the first assigned placebo intravaginal ring for 4 weeks

4 weeks

3 visits (in-person), 1 call (telephone)

Rest Period

Participants have a rest period with no ring use for 1-3 weeks

1-3 weeks

1 call (telephone)

Treatment Phase 2

Participants use the second assigned placebo intravaginal ring for 4 weeks

4 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Placebo Intravaginal Ring A
• Placebo Intravaginal Ring B

Trial Overview The study tests the comfort and safety of two non-medicated intravaginal rings that differ in flexibility. Participants will try each ring for four weeks with a break between uses, while also providing feedback through interviews and undergoing health checks.

How Is the Trial Designed?

Group I: Sequence: Placebo Intravaginal Ring B followed by Placebo Intravaginal Ring A Experimental Treatment 2 Interventions

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.

Group II: Sequence: Placebo Intravaginal Ring A followed by Placebo Intravaginal Ring B Experimental Treatment 2 Interventions

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.

Who Is Running the Clinical Trial?

University of Pittsburgh

Lead Sponsor

Trials

1,820

Recruited

16,360,000+

Oak Crest Institute of Science

Collaborator

Trials

3

Recruited

120+

United States Agency for International Development (USAID)

Collaborator

Trials

212

Recruited

1,519,000+

Published Research Related to This Trial

The newly designed vaginal ring, made of Silastic and without medication, was well accepted by participants, with no significant differences in acceptability across different stiffness levels among the 30 women involved in the study.

While some initial complaints such as vaginal discharge and coital problems were reported, these issues decreased significantly by the second cycle and were nearly absent by the third cycle, indicating good tolerance over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The clinical acceptability of a non-medicated vaginal ring. Roumen, F., Dieben, T., Assendorp, R., et al.[2019]

Intravaginal rings (IVRs) are effective for delivering contraceptives and other medications over extended periods, improving compliance and providing benefits like cycle control and symptom relief for conditions such as menorrhagia and polycystic ovarian syndrome.

IVRs are being researched for their potential to deliver antibodies and microbicides, such as dapivirine and tenofovir, to prevent HIV-1 transmission, indicating their versatility in both contraceptive and preventive health applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravaginal rings: controlled release systems for contraception and prevention of transmission of sexually transmitted infections. Friend, DR.[2018]

Intravaginal rings (IVRs) delivering estradiol significantly reduced climacteric symptoms in postmenopausal women, with reductions of 76% in vasomotor symptoms and 44% in psychological symptoms and loss of libido over 20 weeks.

The IVRs were well tolerated and showed beneficial effects on bone metabolism, indicated by a significant decrease in urinary markers of bone resorption, although they did not significantly affect lipoprotein levels or LDL oxidation susceptibility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects on climacteric symptoms, bone and lipoprotein metabolism of hormone replacement therapy delivered by estradiol-releasing intravaginal rings: a pilot study. Farish, E., Barnes, JF., Rankin, M., et al.[2013]

A study involving 47 low-risk women showed that a 90-day intravaginal ring (IVR) designed to prevent both pregnancy and HIV/STIs was generally well-accepted, with 86% rating its flexibility and smoothness positively.

Most women preferred the 3-month IVR over shorter options, indicating a strong demand for a long-lasting multipurpose prevention technology that minimally affects menstrual cycles and is user-controlled.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acceptability of a Long-Acting, Multipurpose Vaginal Ring: Findings from a Phase I Trial in the U.S. and Dominican Republic. Tolley, EE., Zissette, S., Taylor, J., et al.[2022]

In a study involving 24 postmenopausal women over 28 days, the placebo intravaginal ring was found to be acceptable to two-thirds of the participants, indicating a moderate level of tolerance.

However, significant issues such as discomfort, involuntary expulsion of the ring, and partner discomfort were reported, leading to premature discontinuation in five women, highlighting the need for improvements in design or patient education.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient acceptability of and tolerance to a placebo intravaginal ring in hysterectomized women: a pilot study. Spencer, CP., Cooper, AJ., Ross, D., et al.[2019]

In a study involving 166 healthy women over 6 months, the redesigned contraceptive vaginal ring (IVR-2) did not cause any clinically significant lesions on the vaginal or cervical epithelium, indicating its safety for users.

Minor changes in the vaginal and cervical epithelium were observed in some IVR-2 users, but these were not serious and some resolved with continued use, suggesting that while the ring may cause minor changes, it does not lead to significant harm.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized comparison of the effects on vaginal and cervical epithelium of a placebo vaginal ring with non-use of a ring. Weisberg, E., Fraser, IS., Baker, J., et al.[2019]

In a study involving 61 sexually active young women, 59% expressed a likelihood of using the candidate microbicide VivaGel(®) in the future, indicating a moderate level of acceptability for this potential HIV prevention method.

Participants reported issues with all gels tested, including leakage and decreased sexual satisfaction, which could affect adherence to using the gels and ultimately impact the validity of future efficacy trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

"Tell Juliana": acceptability of the candidate microbicide VivaGel® and two placebo gels among ethnically diverse, sexually active young women participating in a phase 1 microbicide study. Carballo-Diéguez, A., Giguere, R., Dolezal, C., et al.[2021]

Intravaginal rings (IVRs) are emerging as effective drug delivery systems that can provide controlled release of medications over weeks or months, making them suitable for compounds that do not work well when taken orally.

The review emphasizes the importance of developing reliable in vitro testing methods to evaluate the drug release performance of IVRs, ensuring that only safe and effective formulations are used in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In Vitro Methods for Evaluating Drug Release of Vaginal Ring Formulations-A Critical Review. Tietz, K., Klein, S.[2020]

In a study using intravaginal rings (IVRs) to deliver the antiretroviral drug IQP-0528 in pigtail macaques, all tested loadings (100%, 50%, and 25%) released drug levels significantly above the effective concentration needed to inhibit viral activity (IC90).

The research indicates that in vitro release tests may not accurately predict in vivo drug release profiles, especially for poorly soluble drugs like IQP-0528, suggesting a need for more reliable methods to evaluate drug delivery systems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Dose Ranging Pharmacokinetic Evaluation of IQP-0528 Released from Intravaginal Rings in Non-Human Primates. Su, JT., Teller, RS., Srinivasan, P., et al.[2020]

Citations