Testing a vaginal insert for HIV prevention

A Phase I Randomized, Placebo-controlled, Double-blind Study to Assess Safety, Pharmacokinetics, and Modeled Pharmacodynamics of a Vaginal Insert Containing Tenofovir Alafenamide and Elvitegravir

This study is testing a new vaginal insert for HIV prevention to see if it is safe and acceptable for people to use.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years to 50 Years
• Sex: Female
• Sponsor: Eastern Virginia Medical School (other)
• Locations: 3 sites (Norfolk, Virginia and 2 other locations)
• Trial ID: NCT06087913 on ClinicalTrials.gov

What this trial studies

This study examines the safety and pharmacokinetics of a vaginal insert containing TAF and EVG, used daily for three days and then every other day for 14 days. Participants will be randomized to receive either the active insert or a placebo, with tissue sampling conducted at various time points post-treatment. The study aims to evaluate the acceptability of the insert among participants through clinical evaluations and in-depth interviews. It will take place across three sites in the USA, Kenya, and South Africa, enrolling approximately 60 participants in total.

Who should consider this trial

Good fit: Ideal candidates are women aged 18 to 50 who are HIV-uninfected and have had vaginal sex.

Not a fit: Patients who are HIV-positive or have significant systemic diseases may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new method for preventing HIV and HSV infections in women.

How similar studies have performed: Other studies have shown promise in similar approaches for HIV prevention, but this specific method is novel.

Eligibility criteria

Inclusion Criteria:

1. Aged 18 to 50 years (inclusive) at Screening.
2. Assigned female sex at birth.
3. Able and willing to provide written informed consent to be screened for and enrolled in MATRIX-001 in one of the study languages (as specified in site SOP).
4. General good health (by volunteer history) without any evidence of clinically significant systemic disease (as determined by Investigator of Record \[IoR\] or designee).
5. Has had vaginal sex and has an intact uterus and cervix.
6. Has a regular and/or predictable bleeding pattern based on the opinion of the investigator, or is oligomenorrheic or amenorrhoeic.
7. HIV-uninfected based on testing performed at Screening and Enrollment (per protocol algorithms in Appendix II).
8. Negative urine pregnancy test at Screening and Enrollment.
9. Protected from pregnancy by an effective contraceptive method as confirmed by site SOP; effective methods include:

   * minimum of 3 months of use of a combined hormonal contraceptive method (except vaginal rings)
   * minimum of 6 months of use of a progestin only contraceptive method or copper IUD
   * Sterilization of participant or partner
   * Correct and consistent condom use (for US site only)
   * Abstinence from penile-vaginal intercourse (for US site only)
10. Participants over the age of 21 (inclusive) must have documentation of a Grade 0 Pap smear within the past 3 years prior to Enrollment, per the Female Genital Grading Table for Use in Microbicide Studies Addendum 1 (Dated November 2007) to the DAIDS Table for Grading Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017, or Grade 1 Pap smear at Screening with no treatment required.
11. Normal cervicovaginal mucosa (as defined in MATRIX-001 Study Specific Procedures \[SSP\] manual).
12. Willing and able to comply with protocol requirements, including abstaining from vaginal activity and product use at specified times.
13. Per participant report, if in a relationship, must be in a mutually monogamous relationship with a partner who is not known to be HIV positive or to currently have an STI.

Exclusion Criteria:

1. Per participant report, 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.
2. Currently breastfeeding.
3. Positive HIV test at Screening or Enrollment.
4. History of sensitivity/allergy to any component of the study product, topical anesthetic, cellulose based thrombogenic material, or to both silver nitrate and Monsel's solution.
5. Positive test for Trichomonas vaginalis (TV), Neisseria gonorrhea (GC), Chlamydia trachomatis (CT), Treponema pallidum (Syphilis), or Hepatitis B surface antigen (HBsAg) at Screening or (per participant report) treated for GC, CT, TV, HBsAg or syphilis in the past 12 months.
6. Chronic or acute vulvar, vaginal or cervical symptoms (pain, irritation, spotting/bleeding other than what would be expected from contraceptive use, discharge, etc.).
7. Known bleeding/clotting disorder, including use of anti-coagulation.
8. Need for continued use of any contraindicated concomitant medications (as listed in Appendix III).
9. Participation in any other trial with use of an investigational drug/device within the last 30 days or planned participation in any other investigational trial with use of a drug/device during the study.
10. Participants who previously received an HIV vaccine or HIV broadly neutralizing antibody (bNAb) are not eligible. Individuals may be eligible if they participated in an HIV vaccine or bNAb study but have documentation that they did not receive active product (e.g., placebo recipients).
11. Prior use of PEP or oral PrEP (including FTC/TDF) in the past 4 weeks or any prior use of long-acting systemic PrEP (including cabotegravir or islatravir).
12. Grade 2 or higher pelvic finding or laboratory abnormality, per the DAIDS Table for Grading Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017 and/or Addenda 1 (Female Genital Grading Tables for Use in Microbicide Studies \[Dated November 2007\]) or clinically significant laboratory abnormality as determined by the clinician.
13. 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.
14. Has any other condition that, based on the opinion of the IoR or designee, would preclude provision of informed consent, make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives.

Where this trial is running

Norfolk, Virginia and 2 other locations

• Eastern Virginia Medical School Clinical Research Clinic (EVMS CRC) — Norfolk, Virginia, United States (RECRUITING)
• Kenya Medical Research Institute (KEMRI) — Thika, Kenya (RECRUITING)
• CAPRISA eThekwini Clinical Research Site — Durban, South Africa (RECRUITING)

Study contacts

• Study coordinator: Karen Dominguez, MPH

Conditions: Safety Issues, vaginal insert, HIV, pre-exposure prophylaxis