Male Tolerance Study of Dapivirine Gel Following Multiple Topical Penile Exposures

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety of male genitalia when exposed to dapivirine gel following seven once daily applications.

Official Title
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Male Tolerance Study of Dapivirine Gel Following Multiple Topical Penile Exposures

Conditions
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Topical Penile Exposures

Intervention / Treatment
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* Drug: dapivirine
* Drug: matched placebo
* Drug: universal placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least 18 years of age at Screening, verified per site standard operating procedure (SOP) Able and willing to provide written informed consent to be screened for and take part in the study At Screening, able and willing to provide adequate locator information, as defined per site SOP Able and willing to communicate in written and spoken English HIV-uninfected at Screening per Algorithm in Appendix II In general good health, according to the clinical judgment of the Investigator of Record (IoR) or designee Willing to abstain from vaginal, oral and anal intercourse (including receptive anal intercourse), even with a condom; masturbation, and other activities that may cause irritation or injury to the penis during study participation Willing to abstain from using any genitally-applied preparations (except use of usual cleansing products for genital hygiene) other than the study product during study participation Willing to abstain from non-urgent surgical procedures of the penis/GU area for the duration of study participation (e.g. circumcision) At Screening and Enrollment, agrees not to participate in other research studies involving drugs, medical devices, or genital products for the duration of study participation (until all follow-up visits are completed) Exclusion Criteria: Participant report of any of the following: Known adverse reaction to any of the study products or components of the study products (ever) Post-exposure prophylaxis (PEP) for HIV exposure within 6 months prior to Enrollment Penile procedures (e.g. biopsy, circumcision) within 42 days or less prior to Enrollment Participation in any other research study involving drugs, medical devices, or genital products within 30 days or less prior to Enrollment Within the three months prior to Enrollment, history of a non-gonococcal urethritis and/or sexually transmitted infection (STI), including outbreak of genital herpes or condylomata For uncircumcised men, the treatment of candidal balanoposthitis/ balanitis within 30 days prior to Enrollment History of recurrent dermatosis (e.g. eczema) Non-therapeutic injection drug use in the 12 months prior to Screening Currently using an immunosuppressant (with the exception of local nongenital use of low potency products e.g. inhaled corticosteroid for asthma) Has any of the following laboratory abnormalities at Screening: Hemoglobin < 10.0 g/dL Platelet count < 100,000/mm3 White blood cell count < 2,000 cells/mm3 Alanine transaminase (ALT) and/or aspartate aminotransferase (AST) > 2.5x the site laboratory upper limit of normal (ULN) Serum creatinine > 1.3x the site laboratory ULN Calculated creatinine clearance less than 80 mL/min by the Cockcroft-Gault formula where creatinine clearance in mL/min = (140-age in years) x (weight in kg) x 0.85/72 x serum creatinine in mg/dL Note: Otherwise eligible participants with any of the above exclusionary laboratory results may be re-tested. 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. At Screening or Enrollment, diagnosed with STI or reproductive tract infection (RTI) requiring treatment, per current Centers for Disease Control and Prevention (CDC) guidelines At Screening or Enrollment, has a clinically apparent Grade 1 or higher genital exam finding (observed by study staff) At Screening or Enrollment, has Grade 1 or higher genital or urinary symptoms At Screening or Enrollment, diagnosed with phimosis or hypospadias At Screening or Enrollment, penile, scrotal piercing or penile tattoos observed during genital examination 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 the study objectives

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: matched placebo<br> | Drug: matched placebo<br>* dosage form: gel, no api dosage: 2.5g frequency: once daily duration: 7 days<br>|
| Placebo Comparator: universal placebo<br> | Drug: universal placebo<br>* dosage form: gel, HEC-based dosage: 2.5g frequency: once daily duration: 7 days<br>|
| Active Comparator: dapivirine<br> | Drug: dapivirine<br>* dosage form: gel 0.05% dosage: 2.5g frequency: once daily duration: 7 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the genitourinary safety of dapivirine gel (0.05%), the endpoint was the proportion of men subjected to dapivirine gel or placebo gel experiencing specific, protocol-defined safety events during the study (see description). | Any evidence of Grade 2 or higher male genitourinary adverse event(s) as defined by the DAIDS AE Grading Table Version 1.0, December 2004 (Clarification dated August 2009), Addendum 2 (Male Genital Toxicity Table for Use in Topical Microbicide Studies) | 8 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the pharmacokinetics in plasma following 7 days of once daily penile application of dapivirine gel (0.05%) | Dapivirine concentrations in blood | 8 days | 
| To assess the systemic safety following 7 days of once daily penile application of dapivirine gel (0.05%) | Grade 2 and higher clinical and laboratory adverse events as defined by the DAIDS AE Grading Table Version 1.0, December 2004 (Clarification dated August 2009) and the Male Genital Toxicity Table for Use in Topical Microbicide Studies | 8 days | 
| To assess the acceptability following 7 days of once daily penile application of dapivirine gel (0.05%) | Proportion of participants who at their Final Clinic Visit report via the acceptability questionnaire, that they would be very likely to use the candidate microbicide during sexual intercourse in the future | 8 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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male tolerance, HIV-1, microbicide, dapivirine