Clinical trial NCT03393468: Pharmacokinetic Study of Dapivirine Gel Administered Rectally to HIV-1 Seronegative Adults
Official title: An Open Label Randomized Phase 1 Pharmacokinetic Study of Dapivirine Gel Administered Rectally to HIV-1 Seronegative Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2018-01-08
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to evaluate the pharmacokinetics of dapivirine gel administered rectally to HIV-1 seronegative adults.

Detailed description: This study will evaluate the pharmacokinetics (PK) of dapivirine gel administered rectally to HIV-1 seronegative adults.

Participants will be randomly assigned to two groups: Sequence A or Sequence B. Participants in Sequence A will receive 2.5 g of dapivirine gel administered rectally via an applicator, followed by a 2- to 4-week washout period. Participants will then receive a second dose of up to 10 g of dapivirine gel administered rectally via a coital simulation device. Participants in Sequence B will receive up to 10 g of dapivirine gel administered rectally via a coital simulation device, followed by a 2- to 4-week washout period. Participants will then receive a second dose of 2.5 g of dapivirine gel administered rectally via an applicator.

Participants will be in the study for approximately 1 month and will attend 7 study visits. Study visits may include behavioral assessments, physical examinations, blood and urine collection, throat and anorectal sample collection, and PK sampling.

Eligibility criteria: Inclusion Criteria:

* Men and transgender women who are 18 years or older 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 study 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
* At Screening, history of consensual receptive anal intercourse (RAI) at least once in the past year per participant report
* Willing not to 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 abstain from RAI, receptive oral anal stimulation (i.e., rimming), rectal stimulation via fingers, as well as the insertion of any non-study products into the rectum for 72 hours before and after each study visit

Exclusion Criteria:

* At Screening:

  * Hemoglobin Grade 1 or higher\*
  * Platelet count Grade 1 or higher\*
  * White blood count Grade 2 or higher\*
  * Aspartate aminotransferase (AST) or alanine transaminase (ALT) Grade 1 or higher\*
  * Serum creatinine greater than 1.3 times the site laboratory upper limit of normal (ULN)
  * International normalized ratio (INR) greater than 1.5 times the site laboratory ULN
  * 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, hepatitis B virus (HBV) or hepatitis C virus (HCV)) can be re-tested during the screening process. If a participant is re-tested and a non-exclusionary result is documented within 30 days of providing informed consent for screening, the participant may be enrolled.
* Known adverse reaction to latex or polyurethane (ever)
* Anticipated use of and/or unwillingness to abstain from the following medications during study participation:

  * Anticoagulant medications
  * Aspirin (greater than 81 mg/day)
  * Non-steroidal anti-inflammatory drugs (NSAIDS)
  * Any other drugs that are associated with increased likelihood of bleeding
  * Rectally-administered medications or products containing nonoxynol-9 (N-9) or corticosteroids
  * CYP3A inducer(s) and/or inhibitor(s) as specified in the MTN-033 Study Specific Procedures (SSP) Manual
  * Hormone-replacement therapy in tablet, patch, injectable or gel form
* Known adverse reaction to any of the components of the study product, applicator or coital simulation device
* Use of pre-exposure prophylaxis (PrEP) for HIV prevention within 1 month prior to Enrollment, and/or anticipated use and/or unwillingness to abstain from PrEP during trial participation
* Use of post-exposure prophylaxis (PEP) for potential HIV exposure within the 6 months prior to Enrollment
* 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 6 months prior to Enrollment
* Non-therapeutic injection drug use in the 12 months prior to Enrollment
* Participation in research studies involving drugs, medical devices, genital or rectal products, or vaccines within 30 days of the Enrollment Visit
* Per participant report at Screening, treatment of an anogenital sexually transmitted infection (STI) (after diagnosis) within the past 3 months
* At Screening, participant-reported symptoms, and/or clinical or laboratory diagnosis of active anorectal or reproductive tract infection (RTI) requiring treatment per current CDC guidelines (http://www.cdc.gov/std/treatment) 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, chancroid, trichomoniasis.

  * Note: Otherwise eligible participants with an exclusionary UTI may be re-tested during the screening process.
* At Enrollment, active anorectal infection or RTI requiring treatment per current CDC guidelines (http://www.cdc.gov/std/treatment) or symptomatic UTI. Infections requiring treatment include symptomatic GC, CT, syphilis, active HSV lesions, anogenital sores or ulcers, symptomatic genital warts, trichomoniasis, chancroid.

  * 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.

Primary outcomes:
measure: Measurement of dapivirine concentrations in rectal fluid
timeFrame: Measured through approximately 1 month
measure: Measurement of dapivirine concentrations in plasma
timeFrame: Measured through approximately 1 month
measure: Measurement of dapivirine concentrations in rectal mucosal tissue homogenates
timeFrame: Measured through approximately 1 month
Secondary outcomes:
measure: Frequency of Grade 2 or higher adverse events (AEs)
timeFrame: Measured through approximately 1 month
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: University of Pittsburgh CRS
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Ken Ho, MD
role: STUDY_CHAIR
References: