Safety and Acceptability Study of a Non-Hormonal Ring

• ClinicalTrials.gov Identifier: NCT03598088
• Recruitment Status: Completed
• First Posted: July 26, 2018
• Results First Posted: June 8, 2022
• Last Update Posted: June 8, 2022
• Sponsor: Daré Bioscience, Inc.
• Collaborator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Information provided by (Responsible Party): Daré Bioscience, Inc.

Study Description

Brief Summary:

This is a feasibility, multi-center, open-label, non-significant risk device study for a non-hormonal contraceptive ring.

Condition or disease	Intervention/treatment	Phase
Contraception	Device: Ovaprene	Not Applicable

Detailed Description:

The purpose of this clinical trial is to assess the ability of Ovaprene™ to prevent sperm from penetrating midcycle cervical mucus. In addition, safety, release of ingredients, acceptability and fit will be assessed.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 38 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Device Feasibility
• Official Title: Safety and Acceptability Study of a Non-Hormonal Ring
• Actual Study Start Date: May 23, 2018
• Actual Primary Completion Date: October 17, 2019
• Actual Study Completion Date: November 15, 2019

Arms and Interventions

Arm

Intervention/treatment

Healthy Sexually Active Women; Healthy, sexually active women who are not at risk for pregnancy due to previous female tubal sterilization will receive both Ovaprene and the Caya diaphragm throughout the course of the trial. The purpose of the Caya Post Coital Test (PCT) cycle is to ensure that in this study population and at these sites, results that are expected to be observed in a PCT cycle with an approved vaginal barrier can be replicated.

Device: Ovaprene; non-hormonal contraceptive ring

Outcome Measures

Primary Outcome Measures :

1. Changes From Baseline in the Post Coital Test Results (PCT) Due to Device Use. [ Time Frame: Baseline to OVP PCTa at 175 Days ]
   All participants had fewer than 5 progressively motile sperm per high power field (PMS/HPF) in all cycles during Ovaprene use.

Other Outcome Measures:

1. Changes in Cervicovaginal pH Pre-coitus and Post-coitus in the Absence of the Study Device. [ Time Frame: Pre-Intercourse (Baseline Visit 1) and Post-Intercourse (Baseline Visit 2) (24hrs) ]
   Evaluating the change in CVF pH before and after sex with no device present.
2. Changes in Cervicovaginal pH Pre-coitus and Post-coitus in the Presence of the Study Device. [ Time Frame: OVP Cycle A Visit 13 (Day 121) to Visit 14 (Day 122) and OVP Cycle B Visit 18 (Day 156) to Visit 19 (Day 157). ]
   Evaluating the change in CVF pH before and after intercourse when the Ovaprene device was being worn during intercourse.
3. Incidence of Treatment Emergent Adverse Events (Safety and Tolerability) During Use of the Device. [ Time Frame: 175 days ]
   Number of participants within the Ovaprene population that experienced a Urogenital treatment emergent adverse event (AE).
4. Number of Participants With Changes in Pelvic Exam Findings From Baseline [ Time Frame: 175 days ]
   Pelvic exams were completed at all 21 visits via a vaginal Colposcopy procedure.
5. Changes From Baseline in Nugent Score [ Time Frame: 175 days ]

   Nugent scores were calculated prior to the insertion of each Ovaprene device and then after the device was removed at the end of each cycle.

   Nugent score is a gram stain storage system assessing vaginal bacteria present on a scale of 0-10. Scores ranging from 7-10 are indicative of bacterial vaginosis.

6. Changes From Baseline in Antibacterial (Anti-E. Coli) Activity in Cervicovaginal Fluid. [ Time Frame: Pre Baseline (Day 1) to Post Baseline (Day 2); OVP PCTa Pre Intercourse (Visit 13, Day 121) to Post Intercourse (Visit 14, Day 122) and PCTb Pre Intercourse (Visit 18, Day 156) to Post Intercourse (Visit 19, Day 157). ]
   Measuring the E.coli inhibition (%) pre and post intercourse
7. Changes From Baseline in Soluble Markers of Inflammation in Cervicovaginal Fluid. [ Time Frame: Pre Baseline (Day 1) to Post Baseline (Day 2); OVP PCTa Pre Intercourse (Visit 13, Day 121) to Post Intercourse (Visit 14, Day 122) and PCTb Pre Intercourse (Visit 18, Day 156) to Post Intercourse (Visit 19, Day 157). ]
   Measurement of Interleukin-1 Beta (pg IL-1Beta/ug Protein), Interleukin-8 (pg IL-8/ug Protein), Secretory leukocyte Peptidase Inhibitor (SLPI)
8. Number of Participants With a Study Devices That Has Been Worn for One Cycle With Staphylococcus Aureus Presence on Study Device. [ Time Frame: 35 days (one complete cycle) ]
   Vaginal samples and swabs of the used Ovaprene devices were tested for growth of staphylococcus aureus.
9. Number of Devices With Presence of Group A Streptococcus That Have Been Worn for One Cycle. [ Time Frame: 35 days (one full cyle) ]
   Vaginal samples and swabs of the used Ovaprene devices were tested for group A Streptococcus.
10. Summary of the Acceptability of the Study Device Among Male and Female Participants. [ Time Frame: 175 days ]
    Summary of Open-Ended Acceptability Questionnaire
11. Participants Who Could be Fitted With the Ovaprene Device [ Time Frame: Screening or BP3 Visit (2 days) ]
12. Participants That Could Correctly Insert, Position and Remove the Ovaprene Device [ Time Frame: Visit 3 (BP3, Day 15-20); Visit 7 (OS1, Day 84); Visit 12 (OP1a, Day 112); Visit 13 (OP2a, Day 122-132); Visit 17 (OP1b, Day 140); UNS could occur at any point during the 175 day study duration ]
    Number of participants that required written instructions, those who required written and verbal instructions and those who needed physical assistance.
13. Location of Ovaprene in Relation to Cervix [ Time Frame: 175 days ]
    Location was determined digitally and visually by the investigators.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 50 Years (Adult)
• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Females and their male partners to be enrolled.
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

1. Women aged 18-50 years, inclusive
2. General good health, by volunteer history and per investigator judgment
3. History of regular menstrual cycles of 24-35 days (inclusive), by volunteer report
4. History of Pap tests and follow-up consistent with standard medical practice or willing to undergo a Pap test at Visit 1.
5. Protected from pregnancy by female tubal sterilization
6. Willing to abstain from or engage in intercourse with and without condoms and to abstain from other vaginal activity as required in the protocol

7. In a mutually monogamous relationship for at least the last four months with a male partner who:

   1. Is at least 18 years old;
   2. Has no known risk for Sexually Transmitted Infections (STIs);
   3. Is willing and able to comply with protocol requirements including sexual activity/ abstinence and condom use requirements; and
   4. Can engage in vaginal intercourse with the participant, with and without condoms, as specified in protocol
8. Vaginal and cervical anatomy that, in the opinion of the investigator, lends itself to easy colposcopy and genital tract sample collection
9. Willing to give voluntary consent, sign an informed consent form and comply with study procedures as required by the protocol

Exclusion Criteria:

1. History of hysterectomy
2. Vasectomy in male partner
3. Sterility or known history of sperm dysfunction in male partner
4. Within two calendar months from the last pregnancy outcome. Note: If recently pregnant must have had at least two spontaneous menses since pregnancy outcome.
5. Current use of any hormonal contraceptive or a copper IUD (intra-uterine device), or use of Depo-Provera within the last 120 days
6. Currently breastfeeding or having breastfed an infant in the last two months, or planning to breastfeed during the course of the study
7. Significant gynecological abnormalities (including abnormal vaginal bleeding or excessive vaginal discharge)
8. Either device does not appropriately fit volunteer, as determined by clinician
9. Inability of the volunteer to insert, position, and/or remove either device, even with assistance
10. History of sensitivity/allergy to nonoxynol-9 or to silicone or any other component of Ovaprene™ or Caya, for either the volunteer or her male partner
11. In the last four months, either the volunteer or her male partner diagnosed with or treated for any STI or pelvic inflammatory disease. Note: Women or male partners with a history of genital herpes or condylomata who have been asymptomatic for at least six months may be considered for eligibility
12. Positive test for Trichomonas vaginalis, Neisseria gonorrhea, Chlamydia trachomatis, or HIV
13. Deep epithelial genital findings such as abrasions, ulcerations, and lacerations, or vesicles suspicious for a sexually transmitted infection
14. Chronic or acute vulvar or vaginal symptoms (pain, irritation, spotting, etc.)
15. Known current drug or alcohol abuse which could impact study compliance. (This is defined as any illicit drug use or more than 15 alcoholic drinks per week)
16. Participation in any other investigational trial within the last 30 days or planned participation in any other investigational trial during the study
17. History of gynecological procedures (including genital piercing) on the external genitalia, vagina or cervix within the last 14 days
18. Abnormal finding on laboratory or physical examination or a social or medical condition in either the volunteer or her male partner which, in the opinion of the investigator, would make participation in the study unsafe or would complicate interpretation of data
19. Nugent score greater than or equal to 7
20. Systemic use in the last two weeks or anticipated use during the study of antibiotics (other than those used to treat urinary tract infection (UTI), vaginal candidiasis, or bacterial vaginosis (BV) diagnosed at Visit 1, or to treat UTI or vaginal candidiasis after Visit 1) or topical antivirals (e.g., acyclovir or valacyclovir). Note: Participants should avoid non-steroidal anti-inflammatory drugs (NSAIDs) and Tylenol except for occasional use, as in treatment of headaches or dysmenorrhea.
21. Grade 2 or higher abnormality per the March 2017 update of the Division of AIDS (DAIDS), National Institute of Allergy and Infectious Disease (NIAID) Table for Grading of the Severity of Adverse Events or clinically significant lab abnormalities as determined by the investigator (see Section 13.5 for link to DAIDS table)
22. Inability to achieve adequate cervical mucus in two attempts at the baseline cycle
23. Inadequate sperm in endocervical aspirate during baseline testing without any device, despite adequate mucus and presence of sperm in vaginal pool

Contacts and Locations

Locations

United States, California

University of California at Davis

Sacramento, California, United States, 95817

United States, Florida

Segal Trials

North Miami, Florida, United States, 33161

United States, Idaho

Clinical Research Prime

Idaho Falls, Idaho, United States, 83404

United States, Oregon

Oregon Health and Science University

Portland, Oregon, United States, 97239

United States, Pennsylvania

University of Pennsylvania Penn Obstetric Gynecology Associates

Philadelphia, Pennsylvania, United States, 19104

United States, Virginia

Eastern Virginia Medical School

Norfolk, Virginia, United States, 23507

Sponsors and Collaborators

Daré Bioscience, Inc.

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

• Study Director: Nadene A. Zack, MS; Sr Director, Clinical Operations

  Study Documents (Full-Text)

Documents provided by Daré Bioscience, Inc.:

Study Protocol  [PDF] June 13, 2019

Statistical Analysis Plan  [PDF] December 6, 2019

More Information

• Responsible Party: Daré Bioscience, Inc.
• ClinicalTrials.gov Identifier: NCT03598088
• Other Study ID Numbers: DR-OVP-001; 1R44HD095724-01 ( U.S. NIH Grant/Contract )
• First Posted: July 26, 2018
• Results First Posted: June 8, 2022
• Last Update Posted: June 8, 2022
• Last Verified: June 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes
• Product Manufactured in and Exported from the U.S.: No