Safety and Pharmacokinetic Study of Dapivirine Gel (0.05%) Administered Rectally to HIV-1 Seronegative Adults

NCT03239483 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: MTN-02612021
• Study Type: interventional
• Target: 28
• Locations: 2 countries
• Sites: 3

Brief Summary

The purpose of this study is to evaluate the safety and pharmacokinetics (PK) of dapivirine gel (0.05%) administered rectally to HIV-1 seronegative adults.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (5)

• Frequency of Grade 2 or Higher Adverse Events (AEs)

  As defined by the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017 and/or Addenda 1, 2 and 3 (Female Genital \[Dated November 2007\], Male Genital \[Dated November 2007\] and Rectal \[Clarification Dated May 2012\] Grading Tables for Use in Microbicide Studies)

  Measured after the participant has started study product until the participant's study termination at approximately Day 40

• Measurement of Dapivirine Concentrations in Plasma

  As assessed by pharmacokinetic sampling and analysis

  Sample collected at approximately 1, 2, 24, 48 and 72 hours after first single dose, 24 hours after first dose during daily dosing, before last dose and 1,2, 24,48, and 72 hours after last dose.

• Measurement of Dapivirine Concentrations in Rectal Fluid

  As assessed by pharmacokinetic rectal fluid sampling and analysis

  Sample collected at approximately 1, 2, 24, 48 and 72 hours after first single dose, 24 hours after first dose during daily dosing, and 1,2, 24,48, and 72 hours after last dose.

• Measurement of Dapivirine Concentrations in Rectal Mucosal Tissue Homogenates

  As assessed by pharmacokinetic rectal mucosal tissue homogenates sampling and analysis

  Sample collected at approximately 1, 2, 24, 48 and 72 hours after first single dose and 1,2, 24,48, and 72 hours after last dose.

• Terminal Half-life of Dapivirine Concentrations in Plasma

  The terminal half-life of dapivirine in plasma samples was estimated by fitting a linear regression on the log-transformed concentrations from the 24, 48 and 72 hour time-points after the single and multiple doses.Each regression model includes an adjustment for the difference in concentration after multiple dosing. For each participant, Beta was calculated as the negative of the slope of their repression and half-life was log(2)/Beta. Due to the large number of concentrations below the limit of quantification after the single dose, the estimateion of Beta and half-life relied only on concentration after the multiple dosing for most of the participants.

  From samples collected 24 hours after first dose to 72 hours after last daily dose

Secondary Outcomes (2)

• Acceptability: Ease of Use

  after completing the study (study day 40)

• Acceptability: Comfort

  after completing the study (study day 40)

Study Arms (2)

Dapivirine gel

EXPERIMENTAL

Participants will receive a single dose of dapivirine gel rectally, followed by 7 daily doses of dapivirine gel to be administered under direct observation in the clinic.

Drug: Dapivirine gel

Placebo gel

PLACEBO COMPARATOR

Participants will receive a single dose of placebo gel rectally, followed by 7 daily doses of placebo gel to be administered under direct observation in the clinic.

Drug: Placebo gel

Interventions

Dapivirine gel DRUG

Dapivirine gel (0.05%); administered rectally

Dapivirine gel

Placebo gel DRUG

Universal HEC placebo gel; administered rectally

Placebo gel

Eligibility Criteria

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

You may qualify if:

• Age of 18 - 45 years (inclusive) at Screening, verified per site standard operating procedure (SOP)
• Able and willing to provide written informed consent
• HIV-1/2 uninfected at Screening and Enrollment, per applicable algorithm in Appendix II of the protocol and willing to receive HIV test results
• Able and willing to provide adequate locator information, as defined in site SOP
• Available to return for all study visits and willing to comply with study participation requirements
• In general good health at Screening and Enrollment, as determined by the site Investigator of Record (IoR) or designee
• Per participant report, a history of consensual receptive anal intercourse (RAI) at least once in the past calendar year
• Willing to not take part in other research studies involving drugs, medical devices, genital or rectal products, or vaccines for the duration of study participation, including the time between Screening and Enrollment
• Willing to be sexually abstinent for 72 hours prior to each study visit, during the study product use periods and for 72 hours after biopsy collection. Note: See Criteria 12 and 13 for additional restrictions for female participants
• Willing to abstain from inserting any non-study products into the rectum for 72 hours prior to each study visit and during the study product use periods. Note: See Criteria 12 and 13 for additional restrictions for female participants
• Women over the age of 21 (inclusive) must have documentation of a satisfactory Pap within the past 3 years prior to Enrollment consistent with Grade 0 according to 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 satisfactory evaluation with no treatment required of Grade 1 or higher Pap result
• Willing to be sexually abstinent for 72 hours prior to each study visit and during the study product use periods and for 7 days after biopsy collection
• Willing to abstain from inserting any non-study products into the vagina for 72 hours prior to each study visit, during the study product use periods and for 7 days after biopsy collection
• Willing to use 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 and/or partner, as defined in site SOPs), or sexually abstinent for 90 days prior to Screening

You may not qualify if:

• At Screening:
• Hemoglobin Grade 1 or higher\*
• Platelet count Grade 1 or higher\*
• White blood count Grade 2 or higher\*
• Serum creatinine greater than 1.3× the site laboratory upper limit of normal (ULN)
• International normalized ratio (INR) greater than 1.5× the site laboratory ULN
• Aspartate aminotransferase (AST) or alanine transaminase (ALT) Grade 1 or higher\*
• Positive for hepatitis C antibody
• Positive for hepatitis B surface antigen
• History of inflammatory bowel disease by participant report
• \*As per the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events Corrected Version 2.1, July 2017
• Anticipated use of and/or unwillingness to abstain from the following medications during study participation:
• Heparin, including Lovenox®
• Warfarin
• Plavix® (clopidogrel bisulfate)

Sponsors & Collaborators

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

Study Sites (3)

Alabama CRS

Birmingham, Alabama, 35294, United States

Location

University of Pittsburgh CRS

Pittsburgh, Pennsylvania, 15213, United States

Location

Silom Community Clinic CRS

Nonthaburi, Bangkok, 11000, Thailand

Location

Related Publications (2)

• Bauermeister JA, Tingler RC, Dominguez C, Dunne EF, Hoesley C, Ho K, Johnson S, Lucas J, Macagna N, Brown E, Gundacker H, Peda M, Jacobson CE, Kramzer L, Singh D, Dezzutti CS, Ayudhya RPKN, Marzinke MA, Piper J, Devlin B, Nuttall J, McGowan I, Hendrix CW, Cranston RD; MTN 026 team. Acceptability of a Dapivirine/Placebo Gel Administered Rectally to HIV-1 Seronegative Adults (MTN-026). AIDS Behav. 2022 May;26(5):1333-1346. doi: 10.1007/s10461-021-03490-8. Epub 2021 Oct 17.

  PMID: 34657218 DERIVED

• Cranston RD, Brown E, Bauermeister J, Dunne EF, Hoesley C, Ho K, Johnson S, Lucas J, Dominguez-Islas C, Gundacker H, Peda M, Jacobson CE, Kramzer L, Singh D, Dezzutti CS, Kunjara Na Ayudhya RP, Brand RM, Wang L, Marzinke MA, Piper J, Devlin B, Nuttall J, McGowan I, Hendrix CW. A Randomized, Double Blind, Placebo-Controlled, Phase 1 Safety, and Pharmacokinetic Study of Dapivirine Gel (0.05%) Administered Rectally to HIV-1 Seronegative Adults (MTN-026). AIDS Res Hum Retroviruses. 2022 Apr;38(4):257-268. doi: 10.1089/AID.2021.0071. Epub 2021 Dec 6.

  PMID: 34498980 DERIVED

MeSH Terms

Conditions

HIV Infections

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

Results Point of Contact

• Title: Dr. Ross D. Cranston
• Organization: Fundacio Lluita Contra la Sida, Hospital Universitari Germans Trias | Pujol

rdcranston@outlook.com

34-934-657-897

Study Officials

• Ross D. Cranston, MD, FRCP

  Fundació Lluita Contra la Sida, Hospital Universitari Germans Trias I Pujol

  STUDY CHAIR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: August 2, 2017
• First Posted: August 4, 2017
• Study Start: October 26, 2017
• Primary Completion: September 20, 2018
• Study Completion: September 20, 2018
• Last Updated: October 19, 2021
• Results First Posted: November 7, 2019

Record last verified: 2019-10

Locations

TH (1); US (2)