Safety and Pharmacokinetics of Dapivirine Vaginal Ring in Post-menopausal Women

NCT02010593 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: MTN-024/IPM0315UM1AI068633-07
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 3

Brief Summary

This study will evaluate the safety of the dapivirine vaginal ring when inserts once every 4 weeks in postmenopausal women over 12 weeks of product use.

Conditions

Human Immunodeficiency Virus

Outcome Measures

Primary Outcomes (1)

• Safety of Dapivirine (25 mg) Administered in a Silicone Elastomer Vaginal Matrix Ring in HIV-uninfected Postmenopausal Women, When Inserted Once Every 4 Weeks During 12 Weeks of Study Product Use

  Evidence of Grade 2 or higher genital, genitourinary and reproductive system AEs as defined by the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Dec 2004 (Clarification dated August 2009), Addendum 1, (Female Genital Grading Table for Use in Microbicide Studies) judged to be related to study product. Evidence of Grade 3 or higher AEs as defined by the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Dec 2004 (Clarification dated August 2009). DAIDS severity grades are defined as follows: * Grade 1 = mild * Grade 2 = moderate * Grade 3 = severe * Grade 4 = potentially life-threatening * Grade 5 = death

  over 12-week period of use

Secondary Outcomes (4)

• The Percentage of Participants Who Find the Study Vaginal Ring to be as Acceptable

  at 12-week visit

• Percentage of Women Who Were Adherent to Daily Study Product Use Based on Self-report Over the 12-week Study Product Use Period

  12-week period of use

• Pharmacokinetics - The Intent is to Determine if the Plasma Dapivirine Concentrations Are Different in Postmenopausal Women Than in Pre-menopausal Adult Women After Placement of Dapivirine Vaginal Rings.

  a 12 week product use period

• Pharmacokinetics - The Intent is to Determine if the Vaginal Fluid Dapivirine Concentrations Are Different in Postmenopausal Women Than in Pre-menopausal Adult Women After Placement of Dapivirine Vaginal Rings.

  a 12 week product use period

Study Arms (2)

Dapivirine Vaginal Ring

EXPERIMENTAL

Safety study of a vaginal ring containing Dapivirine in a postmenopausal female population

Drug: Dapivirine Vaginal Ring

Placebo

PLACEBO COMPARATOR

The placebo VR is a flexible, platinum-catalyzed-cured matrix ring, identical to Dapivirine Ring-004, containing no active-drug

Drug: Placebo Vaginal Ring

Interventions

Dapivirine Vaginal Ring DRUG

Dapivirine, a non-nucleoside reverse-transcriptase inhibitor (NNRTI), is a substituted amino- pyrimidine (DAPY) derivative with potent antiviral activity against HIV-1. Dapivirine is chemically described as 4-\[\[4-\[(2,4,6-trimethylphenyl)amino\]-2- pyrimidinyl\]amino\]benzonitrile.6 The dapivirine matrix VR is a flexible ring containing 25 mg of drug substance dispersed in a platinum-catalyzed-cured silicone matrix. Dapivirine is known to be well-suited for delivery via VR

Also known as: TMC-120

Dapivirine Vaginal Ring

Placebo Vaginal Ring DRUG

The placebo VR is a flexible, platinum-catalyzed-cured silicone matrix ring, identical to dapivirine Ring-004, containing no active drug.

Placebo

Eligibility Criteria

• Age: 45 Years - 65 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 45 through 65 years (inclusive) at Screening, verified per site SOPs
• Per participant report, postmenopausal at Screening, defined as amenorrhoeic for the past 12 months (minimum) or at least 6 months status post-bilateral oophorectomy
• Follicle-stimulating hormone (FSH) level at 40 mIU/ml or higher at Screening
• Able and willing to provide written informed consent to be screened for and enrolled in MTN-024/IPM 031
• Able to communicate in spoken and written English
• Able and willing to comply with all study procedural requirements
• Willing to only use study provided and/or approved vaginal products throughout the duration of study participation.
• Willing to abstain from inserting study approved lubricant into the vagina for 72 hours prior to each visit
• Willing to abstain from vaginal intercourse for 72 hours prior to each visit
• In general good health as determined by the Investigator of Record (IoR)/designee at Screening and Enrollment
• Able and willing to provide adequate locator information, as defined in site SOPs
• HIV-uninfected based on testing performed at Screening (per protocol algorithm in Appendix II)
• Per participant report at Screening and Enrollment, agrees to use male latex condoms for sexual intercourse
• Per participant report at Screening and Enrollment, states a willingness to refrain from inserting any non-study vaginal products or objects into the vagina including, but not limited to spermicides, female condoms, diaphragms, topical or systemic hormone replacement therapy, including vaginal estrogens, and/or hormonal contraceptives, vaginal medications, menstrual cups, cervical caps (or any other vaginal barrier method), vaginal douches, lubricants and moisturizers, sex toys (vibrators, dildos, etc.), for the duration of the study participation.
• Note: Use of study approved lubricant is permitted.

You may not qualify if:

• Per participant report at screening:
• Plans to relocate away from the study site during study participation
• Plans to travel away from the study site for more than 4 consecutive weeks during study participation
• Diagnosed with urinary tract infection (UTI) at Screening or Enrollment Note: Otherwise eligible participants diagnosed with UTI during screening are offered treatment and may be enrolled after completing treatment and all symptoms have resolved.
• If treatment is completed and symptoms have resolved within 45 days of obtaining informed consent for screening, the participant may be enrolled.
• Diagnosed with pelvic inflammatory disease, an STI or reproductive tract infection (RTI) requiring treatment per current Centers for Disease Control and Prevention (CDC) guidelines at Screening or Enrollment Note: Otherwise eligible participants diagnosed during screening with pelvic inflammatory disease or STI/RTI requiring treatment per CDC guidelines - other than asymptomatic bacterial vaginosis (BV) and asymptomatic candidiasis - are offered treatment and may be enrolled after completing treatment and all symptoms have resolved. If treatment is completed and symptoms have resolved within 45 days of obtaining informed consent for screening, the participant may be enrolled. Genital warts requiring treatment also must be treated prior to Enrollment. Genital warts requiring therapy are defined as those that cause undue burden or discomfort to the participant, including bulky size, unacceptable appearance, or physical discomfort.
• Participant report and/or clinical evidence of any of the following:
• Known adverse reaction to any of the study products (ever)
• Known adverse reaction to latex (ever)
• Chronic and/or recurrent vaginal candidiasis
• Topical or systemic hormone replacement therapy and/or hormonal contraception within the 6 months prior to Enrollment
• Non-therapeutic injection drug use in the 12 months prior to Enrollment
• Post-exposure prophylaxis (PEP) for HIV exposure within the 6 months prior to Enrollment
• Pre-exposure prophylaxis (PrEP) for HIV prevention within the 6 months prior to Enrollment
• Last pregnancy outcome 6 months or less prior to Enrollment

Sponsors & Collaborators

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

Study Sites (3)

Alabama CRS, 84519th Street South, BBRB 203A

Birmingham, Alabama, 35294-2170, United States

Location

Case CRS, Case Western Reserve University, 2061 Cornell Road, Room 303

Cleveland, Ohio, 44106, United States

Location

Magee Women's Hospital of UPMC

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (2)

• Shapley-Quinn MK, Laborde N, Luecke E, Hoesley C, Salata RA, Johnson S, Nel A, Soto-Torres L, Chen BA, van der Straten A. Acceptability of the Dapivirine Vaginal Ring in Postmenopausal US Women. AIDS Patient Care STDS. 2022 Mar;36(3):97-105. doi: 10.1089/apc.2022.0002.

  PMID: 35289688 DERIVED

• Chen BA, Zhang J, Gundacker HM, Hendrix CW, Hoesley CJ, Salata RA, Dezzutti CS, van der Straten A, Hall WB, Jacobson CE, Johnson S, McGowan I, Nel AM, Soto-Torres L, Marzinke MA; MTN-024/IPM 031 Protocol Team for the Microbicide Trials Network. Phase 2a Safety, Pharmacokinetics, and Acceptability of Dapivirine Vaginal Rings in US Postmenopausal Women. Clin Infect Dis. 2019 Mar 19;68(7):1144-1151. doi: 10.1093/cid/ciy654.

  PMID: 30289485 DERIVED

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

Dapivirine

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

The AEs reported were not unexpected in post-menopausal women. Due to the lack of a non-interventional arm or observational period, however, an objective evaluation of possible genital tract AEs associated with vaginal ring (VR) use could not be made.

Results Point of Contact

• Title: Dr John Steytler
• Organization: International Partnership for Microbicides

jsteytler@ipmglobal.org

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 14, 2013
• First Posted: December 13, 2013
• Study Start: December 1, 2013
• Primary Completion: April 1, 2015
• Study Completion: April 1, 2015
• Last Updated: November 3, 2022
• Results First Posted: October 5, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)