Clinical Trials

MainTitle

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

This study is currently recruiting participants. (see Contacts and Locations)

Verified November 2017 by National Institute of Allergy and Infectious Diseases (NIAID)

Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)


Information provided by (Responsible Party)
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier
NCT03239483

First received: August 2, 2017
Last updated: November 13, 2017
Last Verified: November 2017
History of Changes
Purpose

Purpose

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.

Condition Intervention Phase
HIV Infections

Drug : Dapivirine gel
Drug : Placebo gel
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Randomized, Double Blind, Placebo-Controlled, Phase 1 Safety and Pharmacokinetic Study of Dapivirine Gel (0.05%) Administered Rectally to HIV-1 Seronegative Adults

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures

  • Frequency of Grade 2 or higher adverse events (AEs) [ Time Frame: Measured through participants' last study visit at approximately Day 40 ]
    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)
  • Measurement of dapivirine concentrations in plasma [ Time Frame: Measured through participants' last study visit at approximately Day 40 ]
    As assessed by pharmacokinetic sampling and analysis
  • Measurement of dapivirine concentrations in rectal fluid [ Time Frame: Measured through participants' last study visit at approximately Day 40 ]
    As assessed by pharmacokinetic sampling and analysis
  • Measurement of dapivirine concentrations in rectal mucosal tissue homogenates [ Time Frame: Measured through participants' last study visit at approximately Day 40 ]
    As assessed by pharmacokinetic sampling and analysis

Estimated Enrollment: 27
Study Start Date: October 26, 2017
Estimated Study Completion Date: October 2018
Estimated Primary Completion Date: October 2018 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Experimental: Dapivirine gel
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

Dapivirine gel (0.05%); administered rectally

Placebo Comparator: Placebo gel
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

Universal HEC placebo gel; administered rectally

Detailed Description:

This study will evaluate the safety and pharmacokinetics (PK) of dapivirine gel (0.05%) administered rectally to HIV-1 seronegative adults.
Participants will be randomized to receive a single dose of either rectally administered dapivirine gel (0.05%) or placebo gel at study entry (Day 0). Following a minimum 2-week washout period, participants or study staff will administer daily rectal doses of the assigned gel for 7 consecutive days under direct observation in the clinic.
Participants will be in the study for approximately 40 days, and they will attend 16 study visits. Study visits may include behavioral assessments, physical examinations, blood and urine collection, and pelvic and anorectal sample collection. Some visits will include intensive PK sampling. Study staff will contact participants 1 week after Visit 16 for follow-up safety monitoring.

Eligibility

Eligibility

Ages Eligible for Study: 18 Years to 45 Years  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: Yes  

Criteria

Inclusion Criteria:

  • 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

  • Females must also meet the following additional inclusion criteria to be eligible for study inclusion:
  • 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


Exclusion Criteria:
  • 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
    • Note: Otherwise eligible participants with an exclusionary test result (other than HIV, HBV or HCV) can be re-tested during the screening process. If a participant is re-tested and a non-exclusionary result is documented within 45 days of providing informed consent for screening, the participant may be enrolled.
  • Anticipated use of and/or unwillingness to abstain from the following medications during study participation:
    • Heparin, including Lovenox®
    • Warfarin
    • Plavix® (clopidogrel bisulfate)
    • Aspirin (greater than 81 mg)
    • Non-steroidal anti-inflammatory drugs (NSAIDS)
    • Any other drugs that are associated with increased likelihood of bleeding
    • CYP3A inducer(s) and/or inhibitor(s) as specified in the MTN-026 Study-Specific Procedures (SSP) Manual
    • Hormone-replacement therapy in tablet, injectable or gel form
  • Known adverse reaction to any of the components of the study products
  • Use of post-exposure prophylaxis (PEP) for potential HIV exposure within the 6 months prior to Enrollment
  • Use of pre-exposure prophylaxis (PrEP) for HIV prevention within the 6 months prior to Enrollment, and/or anticipated use during trial participation
  • Use of systemic immunomodulatory medications within the 6 months prior to Enrollment, and/or anticipated use during trial participation
  • RAI without a condom and/or penile-vaginal intercourse with a partner who is known to be HIV-positive in the past 6 months
  • Non-therapeutic injection drug use in the 12 months prior to Screening and Enrollment
  • Participation in research studies involving drugs, medical devices, genital or rectal products, or vaccines within 45 days of the Enrollment Visit
  • At Screening, participant report of treatment for an anogenital STI within the past 3 months
  • At Screening, participant-reported symptoms and/or clinical or laboratory diagnosis of active anorectal or reproductive tract infection requiring treatment per current World Health Organization (WHO) guidelines (http://www.who.int/hiv/pub/sti/pub6/en/) or symptomatic urinary tract infection (UTI). Infections requiring treatment include symptomatic Neisseria gonorrhea (GC), Chlamydia trachomatis (CT) infection, syphilis, active herpes simplex virus (HSV) lesions, anogenital sores or ulcers, or symptomatic genital warts, cervicitis, chancroid, pelvic inflammatory disease (PID), bacterial vaginosis (BV), symptomatic vaginal candidiasis, other vaginitis, trichomoniasis. Note: Otherwise eligible participants with an exclusionary UTI, BV and/or candida finding may be re-tested during the screening process.
  • At Enrollment, active anorectal or reproductive tract infection requiring treatment per current WHO guidelines (http://www.who.int/hiv/pub/sti/pub6/en/) or symptomatic urinary tract infection (UTI). Infections requiring treatment include symptomatic GC, CT, syphilis, active HSV lesions, anogenital sores or ulcers, symptomatic genital warts, bacterial vaginosis, symptomatic vaginal candidiasis, other vaginitis, trichomoniasis, chancroid, cervicitis and PID. Note: HSV-1 or HSV-2 seropositive diagnosis with no active lesions is permitted since treatment is not required
  • Has any other condition that, in the opinion of the IoR/designee, would preclude informed consent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving study objectives.

  • Females who meet any of the following additional criteria will be excluded from the study:
  • Pregnant or breastfeeding at either Screening or Enrollment or intends to become pregnant or start breastfeeding during study participation. Note: A documented negative pregnancy test performed by study staff is required for inclusion; however, a self-reported pregnancy is adequate for exclusion from screening/enrollment into the study.
  • Last pregnancy outcome 90 days or less prior to Screening
  • Has had a hysterectomy
  • At Enrollment, has a clinically apparent Grade 1 or higher pelvic exam finding
(observed by study clinician or designee) per the Female Genital Grading Table for Use in Microbicide Studies [Addendum 1, Dated November 2007]. Note: Cervical friability bleeding associated with speculum insertion and/or specimen collection judged to be within the range of normal according to the clinical judgment of the IoR/designee is considered expected non-menstrual bleeding and is not exclusionary.

contacts and locations

Contacts and Locations

Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03239483

Locations

United States, Alabama
Alabama CRS Recruiting
Birmingham, Alabama, United States, 35294
Contact: Edgar T. Overton, M.D    205-934-5191    eoverton@uabmc.edu
United States, Pennsylvania
University of Pittsburgh CRS Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Patricia Peters, R.Ph.    412-383-1434    pep1@pitt.edu
Thailand
Silom Community Clinic CRS Recruiting
Nonthaburi, Bangkok, Thailand, 11000
Contact: Chaiwat Ungsedhapand, M.D.    66-26-446290    yis1@cdc.gov

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Study Chair: Ross D. Cranston, MD, FRCP Fundació Lluita Contra la Sida, Hospital Universitari Germans Trias I Pujol
More Information

More Information


Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)  
ClinicalTrials.gov Identifier: NCT03239483   History of Changes  
Other Study ID Numbers: MTN-026  
  12021  
Study First Received: August 2, 2017  
Last Updated: November 13, 2017  

Studies a U.S. FDA-regulated Drug Product: Yes  
Studies a U.S. FDA-regulated Device Product: No  

Additional relevant MeSH terms:
HIV Infections

ClinicalTrials.gov processed this data on December 15, 2017
This information is provided by ClinicalTrials.gov.