Microbicide Safety and Acceptability in Young Men

NCT01283360 | Completed Phase 1 DMC

• 2 other identifiers: 1009001Grant #:1R01HD059533-01A1
• Study Type: interventional
• Target: 249
• Locations: 2 countries
• Sites: 3

Brief 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.

Conditions

High Risk MSM; HIV Negative; 18-30 Years of Age

Keywords

MSM; HIV negative; microbicide; prevention

Outcome Measures

Primary Outcomes (4)

• Stage 1AB Primary behavioral outcomes

  * Identification of factors related to acceptability and adherence * Proportion of participants who report via the acceptability questionnaire that they would be very likely to use a similar candidate microbicide gel during receptive anal intercourse (RAI) * Proportion of RAI episodes in which the gel was used * Comparison between self-reports of placebo gel use and applicator counts in Stage 1B

  3 months

• Stage 1AB Primary clinical outcome

  the presence of STIs and anal and rectal pathologies as detected by standard anoscopy

  3 months

• Stage 2 Primary clinical outcomes

  Grade 2 or higher AEs, as defined by the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Dec 2004 and/or Addenda 3 (Rectal Grading Tables for Use in Microbicide Studies).

  6 months

• Stage 2 Behavioral

  * Identification of factors related to acceptability and adherence * Proportion of participants who report via the acceptability questionnaire that they would be very likely to use a similar candidate microbicide gel during receptive anal intercourse (RAI) * Proportion of RAI episodes in which the gel was used by participants * Comparison between self-reports of gel use and applicator counts

  6 months

Secondary Outcomes (4)

• Stage 1AB Secondary clinical endpoint

  3 months

• Stage 2 Secondary behavioral outcomes

  6 months

• Stage 1AB Secondary behavioral outcomes

  3 months

• Stage 2 Behavioral

  6 months

Other Outcomes (1)

• Stage 1AB Tertiary Behavioral

  3 months

Study Arms (2)

HEC Placebo Gel

PLACEBO COMPARATOR

In Stage 2, participants will be randomized to receive either 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.

Other: HEC Placebo Gel

Tenofovir 1% Gel

ACTIVE COMPARATOR

In Stage 2, participants will be randomized to receive either 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.

Drug: Tenofovir 1% Gel

Interventions

HEC Placebo Gel OTHER

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.

HEC Placebo Gel

Tenofovir 1% Gel DRUG

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).

Tenofovir 1% Gel

Eligibility Criteria

• Age: 18 Years - 30 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Willing and able to provide written informed consent to take part in the study
• Willing and able to communicate in English or Spanish
• Must agree not to participate in other drug trials
• Biologically male and identifies as male
• Age 18-30 years at screening
• HIV-1 status antibody negative or unknown per patient report
• Understands and agrees to local STI reporting requirements
• Able and willing to provide adequate information for locator purposes
• Availability to return for all study visits, barring unforeseen circumstances
• A history of consensual RAI at least once in past month
• Reporting at least one occasion of unprotected RAI in the prior year\* In order to identify participants at increased risk for acquiring HIV
• Willing and able to provide written informed consent to take part in the study
• Willing and able to communicate in English or Spanish
• Must agree not to participate in other drug trials
• Biologically male, including male-to-female transgender women

You may not qualify if:

• \. Any condition or prior therapy that, in the opinion of the investigator, would make study participation unsafe, make the individual unsuitable for the study or unable to comply with the study requirements. Such conditions may include, but are not limited to, current or recent history of severe, progressive, or uncontrolled substance abuse, or renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, or cerebral disease
• Clinical or laboratory diagnosis of active rectal infection requiring treatment per current CDC guidelines. Infections requiring treatment include Chlamydia (CT), gonorrhea (GC), syphilis, active HSV lesions, chancroid, genital sores or ulcers, and if clinically indicated, genital warts. Note that an HSV-2 seropositive diagnosis with no active lesions is allowed, since treatment is not required
• Positive Hepatitis B surface antigen test indicating hepatitis B infection
• Allergy to methylparaben, propylparaben, or latex
• History of significant drug allergy or recurrent urticaria
• History of inflammatory bowel disease
• Currently engage or plan to engage in unprotected RAI with HIV-infected partners
• By participant report planning to receive another investigational drug while participating in this study
• Any other condition or prior therapy that, in the opinion of the investigator, would make study participation unsafe, make the individual unsuitable for the study or unable to comply with the study requirements. Such conditions may include, but are not limited to, current or recent history of severe, progressive, or uncontrolled substance abuse, or renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, or cerebral disease
• Reporting a history of transactional sex (i.e., having received money or other goods/services in exchange for sex) in the prior 6 months
• Undergoing or completed gender reassignment
• Grade 2 or higher liver function, creatinine, coagulation, electrolyte, or hematology abnormality in accordance with DAIDS toxicity table values (normal values based on site specific laboratory criteria) at screening (or Visit 2 PT/INR for coagulation), and confirmed by retest/and or redraw
• History of significant gastrointestinal bleeding
• History of inflammatory bowel disease
• Abnormalities of the rectal mucosa, or significant rectal symptom(s), which in the opinion of the clinician represents a contraindication to biopsy (including but not limited to presence of any unresolved injury, infectious or inflammatory condition of the local mucosa, and presence of symptomatic external hemorrhoids

Sponsors & Collaborators

• CONRAD: lead
• National Institutes of Health (NIH): collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator
• National Institute of Mental Health (NIMH): collaborator

Study Sites (3)

The Fenway Institute-Fenway Community Health

Boston, Massachusetts, 02215, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

University of Puerto Rico Medical Sciences Campus

San Juan, 00936, Puerto Rico

Location

Related Publications (1)

• McGowan I, Cranston RD, Mayer KH, Febo I, Duffill K, Siegel A, Engstrom JC, Nikiforov A, Park SY, Brand RM, Jacobson C, Giguere R, Dolezal C, Frasca T, Leu CS, Schwartz JL, Carballo-Dieguez A. Project Gel a Randomized Rectal Microbicide Safety and Acceptability Study in Young Men and Transgender Women. PLoS One. 2016 Jun 30;11(6):e0158310. doi: 10.1371/journal.pone.0158310. eCollection 2016.

  PMID: 27362788 DERIVED

MeSH Terms

Interventions

Tenofovir; Gels

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Colloids; Complex Mixtures; Dosage Forms; Pharmaceutical Preparations

Study Officials

• Ian McGowan, MD, PhD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

• Alex Carballo-Dieguez, PhD

  New York State Psychiatric Institute and Columbia University

  PRINCIPAL INVESTIGATOR

• Lynne M. Mofensen, MD

  Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

  STUDY DIRECTOR

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: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2011
• First Posted: January 26, 2011
• Study Start: October 1, 2010
• Primary Completion: May 1, 2013
• Study Completion: May 1, 2013
• Last Updated: May 28, 2015

Record last verified: 2015-05

Locations

PR (1); US (2)