Placebo Intravaginal Rings for Acceptability and Safety

(MATRIX-003 Trial)

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

93 Participants Needed

Trial Summary

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 data supports the idea that Placebo Intravaginal Rings for Acceptability and Safety is an effective treatment?

The available research shows that Placebo Intravaginal Rings are generally well-accepted by users, with most women finding them easy to use and comfortable. However, there is no specific data provided that supports their effectiveness as a treatment for any condition. The studies focus more on the acceptability and potential of intravaginal rings for delivering other drugs, rather than proving the effectiveness of the placebo rings themselves. Therefore, there is no evidence from the provided information that Placebo Intravaginal Rings are an effective treatment. ^{1 2 3 4 5}

What safety data exists for placebo intravaginal rings?

A study involving 166 women using a placebo intravaginal ring (IVR-2) found no clinically significant lesions in the vaginal and cervical epithelium over 6 months. Minor changes like erythema and petechiae were noted, mostly resolving with continued use. The study suggested a link between tampon use and these changes, but not with smoking or intercourse frequency. Overall, the placebo IVR-2 was deemed safe without significant epithelial changes. ^{1 3 4 6 7}

Is the treatment in the trial 'Placebo Intravaginal Rings for Acceptability and Safety' a promising treatment?

Yes, the treatment is promising because intravaginal rings are well-accepted by users, easy to use, and can deliver multiple benefits like contraception and protection against infections. They are also preferred for their long-lasting effects and minimal disruption to daily life. ^{1 3 4 8 9}

What is the purpose of this trial?

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.

Research Team

Catherine A Chappell, MD

Principal Investigator

University of Pittsburgh

Eligibility Criteria

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

I am not sexually active or only have one sexual partner who does not have HIV or any STIs.

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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]

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) 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]

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]

References

1. United States 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. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

In Vitro Methods for Evaluating Drug Release of Vaginal Ring Formulations-A Critical Review. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

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

4. England pubmed.ncbi.nlm.nih.gov

Patient acceptability of and tolerance to a placebo intravaginal ring in hysterectomized women: a pilot study. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

A Dose Ranging Pharmacokinetic Evaluation of IQP-0528 Released from Intravaginal Rings in Non-Human Primates. [2020]

6. United States 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. [2019]

7. United States 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. [2021]

8. England 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. [2013]

9. United States pubmed.ncbi.nlm.nih.gov

The clinical acceptability of a non-medicated vaginal ring. [2019]