Microbicide Safety and Acceptability in Young Men
Condition: High Risk MSM; HIV Negative; 18-30 Years of Age
Study type: Interventional
Phase: Phase 1

Summary: 
      After completing a screening evaluation, 280 eligible participants, including 40 sex workers,
      will be enrolled into Stage 1A of the study during which they will undergo a baseline medical
      evaluation for both history and presence of STIs and anorectal health pathologies or
      injuries, as well as a detailed Web-based baseline behavioral assessment. The first 140
      eligible participants, including 20 sex workers, reporting at least one occasion of
      unprotected RAI in the previous 3 months will be invited to enroll into Stage 1B. In Stage 1B
      participants will apply the universal placebo gel (HEC) rectally prior to each episode of RAI
      over a 3-month period, reporting each use via a phone reporting system; they will complete a
      Web-based questionnaire and take part in a video teleconference at the end of the 3 months.
      The first 24 eligible participants completing Stage 1B will be invited to enroll in Stage 2.
      The subset of sex workers who took part in Stages 1A and 1B will terminate participation at
      the end of 1B. Eligible participants will be randomized to receive either tenofovir 1% gel or
      HEC placebo gel as part of Stage 2, the Phase 1 safety study. Following a baseline visit,
      participants will return to the clinic, where a single dose of the study gel will be
      administered. Within approximately 30 minutes, rectal swab and rectal biopsy specimens will
      be obtained via anoscopy. After a one-week recovery period participants will return to the
      clinic for assessment. If no significant adverse events (AEs) are reported they will begin to
      self-administer once-daily outpatient doses of the study gel for 7 days, after which they
      will return to the clinic for evaluation and specimen collection.
    

Detailed description: 
      Microbicides are products that can be applied in the vagina or rectum to decrease the chances
      of transmission of sexually transmitted infections (STIs) including HIV. In the US, one of
      the most vulnerable groups for acquiring HIV infection is young men, especially young Black
      and Latino men who have sex with men (MSM). This study will be conducted with a young 18-30
      year-old ethnically diverse sample of HIV-negative MSM who report engaging in receptive anal
      intercourse (RAI) using condoms inconsistently or not at all. Our goal is to test whether
      patterns of use of a placebo rectal gel prior to RAI suggest that the product would be used
      correctly and consistently in real life circumstances and whether this highly vulnerable
      population could safely use tenofovir gel, a microbicide candidate. In Version 3.0 of this
      multicentered protocol, a cohort of 40 male and transgender female sex workers were added to
      Stages 1A and 1B in order to determine the feasibility of recruitment and retention of men
      who have sex with men (MSM) with high risk sexual behavior, such as sex workers, for
      microbicide studies, and their likelihood to use noncondom based HIV prevention strategies.
      This study will be conducted by the University of Pittsburgh in collaboration with
      researchers at the HIV Center for Clinical and BehavioralStudies at Columbia University; the
      Fenway Community Health in Boston; and the University of Puerto Rico Clinical Trial Unit in
      San Juan, Puerto Rico. Subjects will be enrolled at the University of Pittsburgh, Fenway
      Community Health, and the University of Puerto Rico. This is a two-stage longitudinal study
      including a clinical and behavioral evaluation (Stage 1A) with an acceptability and adherence
      trial (Stage 1B), followed by a Phase 1 randomized, double-blind, multi-site,
      placebo-controlled trial (Stage 2). Participants who complete Stage 1A are eligible to be
      selected for enrollment into Stage 1B; a similar transition occurs between Stage 1B and Stage
      2.

        -  In Stage 1A, approximately 280 MSM between the ages of 18-30 will be enrolled, including
           a subset of 40 sex workers and will undergo a baseline medical evaluation and a detailed
           Web-based baseline behavioral assessment.

        -  In Stage 1B, approximately 140 participants from Satge 1A, including a subset of 20 sex
           workers, will be asked to apply a placebo gel (HEC) rectally prior to each episode of
           RAI over a 3-month period, reporting each use via a phone reporting system. At the end
           of the 3 months, participants will complete a Web-based questionnaire and take part in a
           video teleconference.The first 42 eligible participants, excluding the mal and
           transgender female sex worker cohort, (approximately 14 at each site) completing Stage
           1B with a reported adherence of 80% or greater will be invited to enroll in Stage 2.

        -  In Stage 2, approximately 24 eligible participants from Stage 1B will progress to Stage
           2 and be randomized at a 1:1 ratio to tenofovir 1% gel or HEC placebo gel.Following a
           baseline visit, participants will return to the clinic, where a single dose of the study
           gel will be administered. Within approximately 30 minutes, rectal swab, stool, and
           rectal biopsy specimens will be obtained via anoscopy. After a one-week recovery period
           participants will return to the clinic for assessment. If no significant adverse
           events(AEs) are reported they will begin to self-administer once-daily outpatient doses
           of the study gel for 7 days, after which they will return to the clinic for evaluation
           and specimen collection.
    

Intervention name(s): HEC Placebo Gel; Tenofovir 1% Gel
Intervention type(s): Other; Drug
Intervention description(s): The HEC universal placebo gel for Stage 2 will be supplied by CONRAD (Arlington, VA, USA). Under direction from CONRAD, DPT Laboratories will manufacture the HEC placebo gel and analyze/release the gels under cGMP. DPT Laboratories will fill the applicators with HEC placebo gel to create pre-filled applicators and package each applicator and plunger in a wrapper. Each pre-filled applicator will contain and deliver a dose of approximately 4 mL of HEC gel.; Tenofovir 1% gel will be supplied by CONRAD (Arlington, VA, USA). Under direction from CONRAD, DPT Laboratories will manufacture the tenofovir 1% gel and analyze/release the gels under cGMP. DPT Laboratories will fill the applicators designed for vaginal use with tenofovir 1% gel to create pre-filled applicators and package each applicator and plunger in a wrapper. Each pre-filled applicator will contain and deliver a dose of approximately 4 mL of tenofovir 1% gel (equal to 4.4 g).
Intervention MeSH terms: Tenofovir
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: MSM; HIV negative; microbicide; prevention