Safety and PK Multi-dose Study of TAF/EVG Vaginal Insert

NCT06087913 | Completed Phase 1 FDA Drug

• 1 other identifier: MATRIX-001
• Study Type: interventional
• Target: 68
• Locations: 3 countries
• Sites: 3

Brief Summary

MATRIX-001 will examine the safety, PK, modeled PD, and acceptability of inserts containing the combination of TAF and EVG applied vaginally, daily for 3 days, then every other day for 14 days. The inserts are ultimately intended to be the basis of an event-driven, on-demand method for prevention of HIV and HSV sexual infection.

Conditions

Safety Issues

Keywords

vaginal insert; HIV; pre-exposure prophylaxis (PrEP)

Outcome Measures

Primary Outcomes (1)

• Number and Severity of Adverse Events

  Safety measured by reported AE's Grade 2 and higher

  Randomization through study completion, an average of 3 months

Secondary Outcomes (7)

• Pharmacokinetics (PK) in cervicovaginal fluid (CVF)

  through completion of study, an average of 3 months

• Pharmacokinetics (PK) in plasma

  through completion of study, an average of 3 months

• Pharmacokinetics (PK) in cervicovaginal tissue

  through completion of study, an average of 3 months

• Modeled in vitro Pharmacodynamics (PD) for HIV

  Enrollment through study completion, an average of 3 months

• Modeled in vitro Pharmacodynamics (PD) for Herpes simplex virus (HSV)

  Enrollment through study completion, an average of 3 months

Other Outcomes (1)

• Modeled Tissue PD

  Enrollment through study completion, an average of 3 months

Study Arms (2)

Active

EXPERIMENTAL

TAF/EVG (20/16mg) vaginal insert

Drug: TAF/EVG vaginal insert

Placebo

PLACEBO COMPARATOR

Matching placebo insert

Drug: Matching Placebo vaginal insert

Interventions

TAF/EVG vaginal insert DRUG

vaginal insert applied daily for 3 days then every other day for 14 days

Active

Matching Placebo vaginal insert DRUG

vaginal insert applied daily for 3 days then every other day for 14 days

Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Aged 18 to 50 years (inclusive) at Screening.
• Assigned female sex at birth.
• 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).
• General good health (by volunteer history) without any evidence of clinically significant systemic disease (as determined by Investigator of Record \[IoR\] or designee).
• Has had vaginal sex and has an intact uterus and cervix.
• Has a regular and/or predictable bleeding pattern based on the opinion of the investigator, or is oligomenorrheic or amenorrhoeic.
• HIV-uninfected based on testing performed at Screening and Enrollment (per protocol algorithms in Appendix II).
• Negative urine pregnancy test at Screening and Enrollment.
• 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)
• 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.

You may not qualify if:

• 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.
• Currently breastfeeding.
• Positive HIV test at Screening or Enrollment.
• 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.
• 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.
• Chronic or acute vulvar, vaginal or cervical symptoms (pain, irritation, spotting/bleeding other than what would be expected from contraceptive use, discharge, etc.).
• Known bleeding/clotting disorder, including use of anti-coagulation.
• Need for continued use of any contraindicated concomitant medications (as listed in Appendix III).
• 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.
• 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).
• 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).

Sponsors & Collaborators

• Eastern Virginia Medical School: lead
• CONRAD: collaborator
• University of Pittsburgh: collaborator
• Centre for the AIDS Programme of Research in South Africa: collaborator
• Kenya Medical Research Institute: collaborator
• United States Agency for International Development (USAID): collaborator

Study Sites (3)

Eastern Virginia Medical School Clinical Research Clinic (EVMS CRC)

Norfolk, Virginia, 23507, United States

Location

Kenya Medical Research Institute (KEMRI)

Thika, Kenya

Location

CAPRISA eThekwini Clinical Research Site

Durban, South Africa

Location

Related Publications (2)

• Dobard CW, Peet MM, Nishiura K, Holder A, Dinh C, Mitchell J, Khalil G, Pan Y, Singh ON, McCormick TJ, Agrahari V, Gupta P, Jonnalagadda S, Heneine W, Clark MR, Garcia-Lerma JG, Doncel GF. Single dose topical inserts containing tenofovir alafenamide fumarate and elvitegravir provide pre- and post-exposure protection against vaginal SHIV infection in macaques. EBioMedicine. 2022 Dec;86:104361. doi: 10.1016/j.ebiom.2022.104361. Epub 2022 Nov 21.

  PMID: 36423375 BACKGROUND

• Thurman AR, Ouattara LA, Yousefieh N, Anderson PL, Bushman LR, Fang X, Hanif H, Clark M, Singh O, Doncel GF. A phase I study to assess safety, pharmacokinetics, and pharmacodynamics of a vaginal insert containing tenofovir alafenamide and elvitegravir. Front Cell Infect Microbiol. 2023 Apr 19;13:1130101. doi: 10.3389/fcimb.2023.1130101. eCollection 2023.

  PMID: 37153145 BACKGROUND

Related Links

• MTN-039 Safety and PK of TAF/EVG rectal insert

Study Officials

• Leila Mansoor, BPharm, PhD

  Centre for the AIDS Programme of Research in South Africa

  STUDY CHAIR

• Nelly Mugo, MBChB

  Kenya Medical Research Institute

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized, Placebo-Controlled, Double-Blind

Study Record Dates

• First Submitted: September 7, 2023
• First Posted: October 18, 2023
• Study Start: November 8, 2023
• Primary Completion: December 2, 2024
• Study Completion: December 2, 2024
• Last Updated: September 2, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1); KE (1); ZA (1)