Current Projects

ATN 163 (DREAM)

A phase-1, open label study of a one-dose tenofovir (TFV) medicated douche.

On demand and behaviorally-congruent forms of HIV pre-exposure prophylaxis (PrEP) have long been demanded by communities at great risk of HIV, especially men who have sex with men (MSM). The DREAM Program is developing a tenofovir (TFV) douche for on demand PrEP use prior to receptive anal intercourse (RAI), given that the vast majority of MSM very commonly douche prior to RAI (behaviorally-congruent). This ATN protocol seeks to ensure the inclusion of adolescent and young adults' (age 15-24 years) perspectives as next generation biomedical prevention, specifically a rectal douche, is being developed for efficacy.

 

ATN DREAM is an early phase 1, open label study to compare the safety, PK, PD, and acceptability of a TFV-medicated douche. Each participant will undergo a Screening Visit to evaluate eligibility. Baseline Visit will assess pre-dose safety, PK, PD, and behavioral points of reference. Safety, PK, PD, and behavioral readouts are assessed at specified times after the single dose. The TFV douche to be used consists of TFV 660 mg in 125 mL half-normal saline (TFV 5.28 mg/mL). Study objectives including safety, pharmacokinetics (PK), pharmacodynamics (PD), and acceptability of a single TFV douche, are essential to inform the design of an extended safety study of a TFV douche in outpatient pre-RAI contexts. The necessity of extending the testing of new HIV prevention modalities to this proposed adolescent population is motivated by anticipated behavioral differences, not biological ones.

 

Participant accrual will take approximately 9 months and each participant will be on study for approximately 3 months. Total study duration is about 1 year.

Primary Outcome Measures:

  1. Change in Tenofovir Diphosphate (TFV-DP) concentration [ Time Frame: At 1 hour, 6 hours, 24 hours, 72 hours after the TFV douche administration]

    • Colonic tissue cell TFV-DP concentrations (femtomoles/million cells) will be measured the study douche administration, based on the individual participant's sampling schedule, on Day 1 (at 1 hour or 6 hours post dose), Day 2 (24 hours post dose), or Day 4 (72 hours post dose).

  2. Acceptability of TFV Douche as assessed by Product Acceptability Questionnaire [ Time Frame: Following administration of study product, up to 1 hour]

    • To analyze study product sequence acceptability, the outcome will be examined in both continuous and dichotomous forms. For each sequence, descriptive statistics of overall acceptability will be generated (i.e., mean and standard deviation for continuous variables and proportion of subjects who consider the sequences acceptable -- with score 3 or greater). The acceptability of each sequence is defined as a mean score of 3 on 4-point continuous acceptability measure (1=completely unacceptable; 2=somewhat unacceptable; 3=somewhat acceptable; 4=highly acceptable) that is defined in this study as the minimal clinically meaningful threshold for sequence acceptability.

  3. Safety of TFV Douche as assessed by the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events [ Time Frame: Following administration of study product, up to 7 days]

    • To evaluate the safety of a single dose of a TFV douche when applied rectally, as measured by the number of ≥Grade 2 adverse events (AEs) as defined by the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, the number and the frequency of all adverse events (AEs) will be tabulated. Safety analyses will also tabulate the number and type of AEs observed overall, and by severity, site, and study product. AEs that lead to discontinuation of study participation will be tabulated separately.

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