A Phase 1, Randomized Pharmacokinetics and Safety Study of Extended Duration Dapivirine Vaginal Rings

NCT03234400 | Completed Phase 1 FDA Drug FDA Device

• 2 other identifiers: MTN-036/IPM 0475UM1AI068633
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 2

Brief Summary

Participants will be randomized to one of three study vaginal rings (VRs) in a 1:1:1 ratio, 25 mg, 100 mg or 200 mg VRs.

Conditions

HIV-1-infection

Outcome Measures

Primary Outcomes (4)

• DPV concentration in plasma.

  To compare the local and systemic pharmacokinetics (PK) of two extended duration DPV VRs (100 mg and 200 mg) when used continuously for 13 weeks to the current 25 mg DPV VR when replaced every 4 weeks for 8 weeks and then worn for an additional 5 weeks for a total of 13 weeks.

  13 weeks

• DPV concentration in cervicovaginal fluid

  To compare the local and systemic pharmacokinetics (PK) of two extended duration DPV VRs (100 mg and 200 mg) when used continuously for 13 weeks to the current 25 mg DPV VR when replaced every 4 weeks for 8 weeks and then worn for an additional 5 weeks for a total of 13 weeks.

  13 weeks

• DPV concentration in cervical tissue

  To compare the local and systemic pharmacokinetics (PK) of two extended duration DPV VRs (100 mg and 200 mg) when used continuously for 13 weeks to the current 25 mg DPV VR when replaced every 4 weeks for 8 weeks and then worn for an additional 5 weeks for a total of 13 weeks.

  13 weeks

• Safety comparison of the two extended duration DPV VRs (100 mg and 200 mg) to the current 25 mg DPV VR

  * Proportions of participants with Grade 2 or higher genitourinary adverse events as defined by the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1, March 2017, and/or Addendum 1 (Female Genital Grading Table for Use in Microbicide Studies \[Dated November 2007\]) * Proportions of participants with Grade 3 or higher adverse events as defined by the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1, March 2017

  13 weeks

Secondary Outcomes (3)

• Adherence

  13 weeks

• Adherence

  13 weeks

• Acceptability

  13 weeks

Study Arms (3)

25 mg Dapivirine Vaginal Ring

EXPERIMENTAL

Participants will insert one Dapivirine Vaginal Ring, 25 mg to be replaced every 4 weeks for 8 weeks, then worn for an additional 5 weeks for a total of 13 weeks. Participants will continue follow-up for an additional one to three days after final VR removal.

Combination Product: Dapivirine Vaginal Ring, 25 mg

100 mg Dapivirine Vaginal Ring

EXPERIMENTAL

Participants will insert one Dapivirine Vaginal Ring, 100 mg to be used continuously for 13 weeks. Participants will continue follow-up for an additional one to three days after final VR removal.

Combination Product: Dapivirine Vaginal Ring, 100 mg

200 mg Dapivirine Vaginal Ring

EXPERIMENTAL

Participants will insert one Dapivirine Vaginal Ring, 200 mg to be used continuously for 13 weeks. Participants will continue follow-up for an additional one to three days after final VR removal.

Combination Product: Dapivirine Vaginal Ring, 200 mg

Interventions

Dapivirine Vaginal Ring, 25 mg COMBINATION_PRODUCT

Vaginal Ring containing 25 mg dapivirine

25 mg Dapivirine Vaginal Ring

Dapivirine Vaginal Ring, 100 mg COMBINATION_PRODUCT

Vaginal Ring containing 100 mg dapivirine

100 mg Dapivirine Vaginal Ring

Dapivirine Vaginal Ring, 200 mg COMBINATION_PRODUCT

Vaginal Ring containing 200 mg dapivirine

200 mg Dapivirine Vaginal Ring

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 SOPs
• Able and willing to provide written informed consent to be screened for and enrolled in MTN-036/IPM 047
• 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 comply with abstinence and other protocol requirements
• Willing to use male condoms for penile-vaginal intercourse (PVI) and penile-rectal 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 ring)
• intrauterine device (IUD)
• sterilization (of participant or partner, as defined in site SOPs)
• having sex exclusively with cis-women
• abstinence from PVI for 90 days prior to Enrollment, and intending to remain abstinent from PVI for the duration of study participation
• HIV-uninfected based on testing performed at Screening and Enrollment

You may not qualify if:

• Pregnant at Screening or Enrollment or plans to become pregnant during the study period
• Diagnosed with a UTI or reproductive tract infection (RTI) at Screening or Enrollment
• Diagnosed with an acute 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 (GC), CT, trichomonas, PID, and/or syphilis
• Has a clinically apparent Grade 2 or higher pelvic exam finding (observed by study staff) at Screening or Enrollment, as per the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1, March 2017, and/or Addendum 1 (Female Genital Grading Table for Use in Microbicide Studies \[Dated November 2007\])
• \) Participant report and/or clinical evidence of any of the following:
• Known adverse reaction to any of the study products (ever)
• 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
• Currently breastfeeding or planning to breastfeed during the study period
• Participation in any other research study involving drugs, medical devices, vaginal 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 Grade 1 or higher laboratory abnormalities at Screening Visit:
• AST or ALT
• Hemoglobin

Sponsors & Collaborators

• International Partnership for Microbicides, Inc.: lead
• National Institutes of Health (NIH): collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (2)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Bridge HIV CRS San Francisco Department of Public Health

San Francisco, California, 94102, United States

Location

Related Publications (2)

• 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

• Liu AY, Dominguez Islas C, Gundacker H, Neradilek B, Hoesley C, van der Straten A, Hendrix CW, Beamer M, Jacobson CE, McClure T, Harrell T, Bunge K, Devlin B, Nuttall J, Spence P, Steytler J, Piper JM, Marzinke MA; MTN-036/IPM 047 Protocol Team for the Microbicide Trials Network. Phase 1 pharmacokinetics and safety study of extended duration dapivirine vaginal rings in the United States. J Int AIDS Soc. 2021 Jun;24(6):e25747. doi: 10.1002/jia2.25747.

  PMID: 34118115 DERIVED

Study Design

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

Study Record Dates

• First Submitted: July 25, 2017
• First Posted: July 31, 2017
• Study Start: December 4, 2017
• Primary Completion: October 23, 2018
• Study Completion: January 23, 2019
• Last Updated: January 29, 2019

Record last verified: 2019-01

Locations

US (2)