Pharmacokinetic and Safety Study of a 90 Day Intravaginal Ring Containing Tenofovir

NCT03670355 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: MTN-03838460
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to evaluate the pharmacokinetics (PK) and safety of a 90-day intravaginal ring (IVR) containing tenofovir (TFV).

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (7)

• Measurement of TFV Levels in Plasma

  TFV concentrations as assessed by drug detection testing in plasma samples collected at multiple timepoints during the study.

  Measured through Day 92

• Measurement of TFV Levels in Cervicovaginal Fluid (CVF)

  TFV concentrations as assessed by drug detection testing in CVF samples collected at multiple timepoints during the study.

  Measured through Day 92

• Measurement of TFV Levels in Rectal Fluid

  TFV concentrations as assessed by drug detection testing in rectal fluid samples collected at multiple timepoints during the study.

  Measured through Day 92

• Measurement of TFV Levels in Cervical Tissue

  TFV concentrations as assessed by drug detection testing in cervical tissue samples collected at multiple timepoints during the study.

  Measured through Day 92

• Measurement of Tenofovir Diphosphate (TFV-DP) Levels in Cervical Tissue

  TFV-DP concentrations as assessed by drug detection testing in cervical tissue samples collected at multiple timepoints during the study.

  Measured through Day 92

• Proportion of Participants With Grade 2 or Higher Genitourinary Adverse Event

  As defined by the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017, and/or Addendum 1 (Female Genital \[Dated November 2007\] Grading Table for Use in Microbicide Studies)

  Measured through Day 92

• Proportion of Participants With Grade 3 or Higher Adverse Event

  As defined by the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017

  Measured through Day 92

Secondary Outcomes (3)

• Number of Participants Fully Adherent to the Study IVR

  Measured through Day 92

• Duration Without IVR in Vagina for Participants Not Fully Adherent

  Measured through Day 92

• Degree to Which Participants Like or Dislike Using the IVR

  Measured on the end of study, Day 92, visit.

Study Arms (2)

Tenofovir (TFV) Intravaginal Ring (IVR)

EXPERIMENTAL

The TFV IVR will be inserted during the enrollment visit (Day 0) and used continuously for approximately 91 days.

Drug: Tenofovir (TFV) IVR

Placebo IVR

PLACEBO COMPARATOR

The placebo IVR will be inserted during the enrollment visit (Day 0) and used continuously for approximately 91 days.

Drug: Placebo IVR

Interventions

Tenofovir (TFV) IVR DRUG

Contains 1.4 g TFV

Tenofovir (TFV) Intravaginal Ring (IVR)

Placebo IVR DRUG

Contains placebo

Placebo IVR

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Assigned female sex at birth
• Note: Participants who are female at birth, who now identify as male, will not be excluded so long as they are not on female-to-male transition therapy.
• Age 18 through 45 years (inclusive) at Screening, verified per site standard operating procedures (SOPs)
• Able and willing to provide written informed consent to be screened for and enrolled in MTN-038
• Able and willing to provide adequate locator information, as defined in site SOPs
• Able to communicate in spoken and written English
• Available for all visits and able and willing to comply with all study procedural requirements
• Willing to abstain from receptive vaginal or anal sexual activities for 72 hours prior to each clinical visit and for 72 hours after biopsy collection
• Willing to use male condoms for penile-vaginal and penile-rectal sexual intercourse for the duration of study participation
• Per participant report, using an effective method of contraception for at least 30 days (inclusive) prior to Enrollment, and intending to continue use of an effective method for the duration of study participation; effective methods include:
• hormonal methods (except contraceptive vaginal ring)
• intrauterine device (IUD)
• sterilization (of participant or partner, as defined in site SOPs)
• having sex exclusively with individuals assigned female sex at birth
• sexually abstinent as defined by abstaining from penile-vaginal intercourse for 90 days prior to Enrollment, and intending to remain abstinent for the duration of study participation

You may not qualify if:

• Pregnant at Screening or Enrollment or plans to become pregnant during the study period
• Diagnosed with symptomatic urinary tract infection (UTI) or reproductive tract infection (RTI) at Screening or Enrollment
• Otherwise eligible participants diagnosed with UTI/RTI during screening will be offered treatment. If treatment is complete and symptoms have resolved within the 45 day screening window, eligible participants may be enrolled.
• Diagnosed with an acute sexually transmitted infection (STI) requiring treatment per current Centers for Disease Control and Prevention (CDC) guidelines (http://www.cdc.gov/std/treatment/) at Screening or Enrollment such as gonorrhea, chlamydia, trichomonas, pelvic inflammatory disease, and/or syphilis
• Has a clinically apparent Grade 2 or higher pelvic exam finding (observed by study staff) at Screening or Enrollment. \*
• Participant report and/or clinical evidence of any of the following:
• Known adverse reaction to any of the study products (ever), including polyurethane
• Chronic and/or recurrent vaginal candidiasis
• Non-therapeutic injection drug use in the 12 months prior to Enrollment
• Last pregnancy outcome less than 90 days prior to Enrollment
• Gynecologic or genital procedure (e.g., tubal ligation, dilation and curettage, piercing) 45 days or less prior to Enrollment
• Currently breastfeeding or planning to breastfeed during the study
• Participation in any other research study involving drugs, medical devices, vaginal or rectal products, or vaccines, in the 60 days prior to Enrollment
• Use of pre-exposure prophylaxis (PrEP) for HIV prevention and/or post-exposure prophylaxis (PEP) for potential HIV exposure within the 3 months prior to Enrollment, and/or anticipated use and/or unwillingness to abstain from PrEP during trial participation
• Has any of the following laboratory abnormalities at Screening Visit:

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (3)

Alabama CRS

Birmingham, Alabama, 35294, United States

Location

Bridge HIV CRS

San Francisco, California, 94143, United States

Location

University of Pittsburgh CRS

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (2)

• Liu AY, Gundacker H, Richardson B, Chen BA, Hoesley C, van der Straten A, Brown A, Beamer M, Robinson J, Jacobson CE, Scheckter R, Bunge K, Schwartz J, Thurman A, Piper JM, Marzinke MA; MTN-038 Protocol Team for the Microbicide Trials Network. Phase 1 randomized pharmacokinetic and safety study of a 90-day tenofovir vaginal ring in the United States. J Int AIDS Soc. 2024 Mar;27(3):e26223. doi: 10.1002/jia2.26223.

  PMID: 38444118 RESULT

• Hawley I, Song M, Scheckter R, McClure T, Piper J, Chen BA, Hoesley C, Liu AY, van der Straten A. Users' Preferred Characteristics of Vaginal Rings for HIV Prevention: A Qualitative Analysis of Two Phase I Trials. AIDS Res Hum Retroviruses. 2022 Apr;38(4):313-326. doi: 10.1089/AID.2021.0077. Epub 2022 Feb 11.

  PMID: 34969254 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

Tenofovir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Albert Liu
• Organization: San Francisco Department of Public Health

albert.liu@sfdph.org

4154377408

Study Officials

• Albert Liu, MD, MPH

  San Francisco Department of Public Health

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2018
• First Posted: September 13, 2018
• Study Start: January 2, 2019
• Primary Completion: September 25, 2019
• Study Completion: September 25, 2019
• Last Updated: November 13, 2025
• Results First Posted: November 13, 2025

Record last verified: 2025-10

Locations

US (3)