A Placebo-Controlled Study Using VP-102 in the Treatment of External Genital Warts

Study Overview
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Brief Summary
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This is a Phase 2, double-blind, placebo-controlled study to determine the dose regimen, safety, tolerability, and efficacy of VP-102 in subjects with External Genital Warts (EGW). This study is divided into two parts (Part A and Part B). Increasing durations of skin exposure to study drug (VP-102 or placebo) will be evaluated in three treatment groups prior to progressing to enrollment in Part B. Part A & B will enroll a approximately 108 subjects completing 4 treatment applications every 21 days and continuing with follow-up assessments at Day 84, 112 and 147.

Detailed Description
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This study is to determine the Dose Regimen, Efficacy, Safety, and Tolerability of VP-102 in Subjects with External Genital Warts. It is divided into two parts (Part A and Part B). The aim of Part A is to determine the two best treatment regimens for evaluation of safety and efficacy in Part B.In Part A, Study drug (VP-102 or placebo) will be administered once every 21 days for up to four applications. Enrollment will begin in Group 1, then proceed into Group 2, and lastly into Group 3. A safety review will be conducted to determine whether enrollment can be initiated into the next Group. An additional blinded safety review will be performed after all six subjects in Group 3 have completed the 48-hour Visit, in order to support dose selection for Part B (Safety and Efficacy). Part B of the study will begin enrollment only after the Sponsor has selected the two dose regimens from Part A. The study will remain blinded until completion of both parts of the study. In Part A, up to 18 subjects will be randomized to VP-102 or placebo treatment with three different regimens. When Part B is open an additional  90 subjects will be enrolled and randomized to VP-102 or placebo with two treatment regimens. Two of the treatment arms will be VP-102 Regimen 1 and VP-102 Regimen 2. The other two treatment arms will be placebo (Placebo Regimen 1 and Placebo Regimen 2), with corresponding durations of skin exposure matching those selected for VP-102 Regimen 1 and Regimen 2. As an example, if the regimens selected from Part A are the 2-hour and 6-hour applications of VP-102, then VP-102 Regimen 1 would be VP-102 treatment for 2-hours and VP-102 Regimen 2 would be VP-102 treatment for 6-hours. Likewise, Placebo Regimen 1 would be placebo treatment for 2 hours and Placebo Regimen 2 would be placebo treatment for 6-hours. Randomization of the four treatment arms (VP-102 Regimen 1:VP-102 Regimen 2:Placebo Regimen 1:Placebo Regimen 2) will be 3:3:2:2. In both Regimen 1 and Regimen 2, study drug will be administered to EGW once every 21 days for up to four applications. Subjects will be asked to remove the study drug at the designated time selected from the dose regimen findings in Part A of the study. Treatment will continue with a minimum of every 21 days, until complete clearance or a maximum of four treatment sessions. Safety assessments including recording of local skin reactions are conducted at each treatment visit and at follow up visits Day 84, 112, and 147.

Official Title
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A Phase 2, Double-Blind, Placebo-Controlled Study to Determine the Dose Regimen, Efficacy, Safety, and Tolerability of VP-102 in Subjects With External Genital Warts

Conditions
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Condylomata Acuminata, Papillomavirus Infections, Skin Diseases, Viral, Skin Diseases, Infectious, Skin Diseases, Sexually Transmitted Diseases, Viral, Sexually Transmitted Diseases, Warts

Intervention / Treatment
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* Combination Product: VP-102 and applicator
* Combination Product: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Be healthy, immunocompetent males or females ≥ 18 years of age Present with ≥ 2 and ≤ 30 external genital and/or perianal warts in ≥ 1 of the following anatomic areas: In both sexes: medial thigh (except inguinal fold); supra-pubic, perineal, and perianal areas In men: over the glans penis (excluding urethral meatus), penis shaft, scrotum, and foreskin In women: vulva (excluding labia minora and mucosal surfaces) Have warts present for ≥ 4 weeks at the baseline visit Have warts that are ≤ 8 mm in diameter each Key Exclusion Criteria: Have a wart within the allowed treatment area > 8 mm in diameter or with an eroded or ulcerated surface, in the Investigator's opinion Have an unclear diagnosis of condyloma Have any wart types other than genital warts (e.g., common or plantar warts) that require treatment during the study period Have active genital herpes eruption, or had active genital herpes lesions within 4 weeks before enrollment Have a history of neoplasia or other HPV-associated malignancies within the last 5 years Are systemically immunosuppressed Are sexually active or may become sexually active and are unwilling to practice responsible birth control methods Are pregnant or breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The aim of Part A is to determine the two best treatment regimens for evaluation of safety and efficacy in Part B. Increasing durations of skin exposure to study drug (VP-102 or placebo) will be evaluated in three treatment groups (n=6/group) that will enroll progressively. Part B of the study will begin enrollment only after the Sponsor has selected the two dose regimens in Part A, which will be called VP-102 Regimen 1 and Regimen 2.Approximately 90 subjects will be enrolled and randomized to one of four treatment arms (two treatment regimens, each with VP-102 and Placebo). Randomization will be stratified by sex so that neither gender exceeds  60% of any treatment arm. Two of the treatment arms will be VP-102 Regimen 1 and VP-102 Regimen 2. The other two treatment arms will be placebo (Placebo Regimen 1 and Placebo Regimen 2), with corresponding durations of skin exposure matching those selected for VP-102 Regimen 1 and Regimen 2.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Part A: VP-102 2 hour-Active<br>For part A, VP-102 will be applied for 2 hours and removed. If selected as a dose regimen for Part B VP-102 will be applied for 2 hours and removed.In both parts, VP-102 is applied every 21 days for 4 treatments. | Combination Product: VP-102 and applicator<br>* In part A, VP-102 will be applied for either 2, 6 or 24 hours with each regimen compared to placebo. For part B, 2 of the regimens from part A will be chosen for Part B with each compared to Placebo. Only 4 arms are actually being studied.<br>* Other names: VP-102 (cantharidin) 0.7% w/v topical solution;|
| Active Comparator: Part A: VP-102 6-hour Active<br>For part A, VP-102 will be applied for 6 hours and removed. If selected as a dose regimen for Part B VP-102 will be applied for 6 hours and removed. In both parts, VP-102 is applied every 21 days for 4 treatments. | Combination Product: VP-102 and applicator<br>* In part A, VP-102 will be applied for either 2, 6 or 24 hours with each regimen compared to placebo. For part B, 2 of the regimens from part A will be chosen for Part B with each compared to Placebo. Only 4 arms are actually being studied.<br>* Other names: VP-102 (cantharidin) 0.7% w/v topical solution;|
| Active Comparator: Part A: VP-102 24-hour Active<br>For part A, VP-102 will be applied for 24 hours and removed. If selected as a dose regimen for Part B, VP-102 will be applied for 24 hours and removed. In both parts, VP-102 is applied every 21 days for 4 treatments. | Combination Product: VP-102 and applicator<br>* In part A, VP-102 will be applied for either 2, 6 or 24 hours with each regimen compared to placebo. For part B, 2 of the regimens from part A will be chosen for Part B with each compared to Placebo. Only 4 arms are actually being studied.<br>* Other names: VP-102 (cantharidin) 0.7% w/v topical solution;|
| Placebo Comparator: Part A: Placebo<br>For part A, VP-102 will be applied for 2-,6- or 24- hours and removed. Placebo is applied every 21 days for 4 treatments. | Combination Product: Placebo<br>* The placebo single-use applicator contains the same formulation as the VP-102 applicator but does not contain the active pharmaceutical ingredient cantharidin<br>|
| Active Comparator: Part B & A: VP-102 6 hour-Active<br>Part B, VP-102 will be applied for 6 hours and removed. VP-102 is applied every 21 days for 4 treatments. | Combination Product: VP-102 and applicator<br>* In part A, VP-102 will be applied for either 2, 6 or 24 hours with each regimen compared to placebo. For part B, 2 of the regimens from part A will be chosen for Part B with each compared to Placebo. Only 4 arms are actually being studied.<br>* Other names: VP-102 (cantharidin) 0.7% w/v topical solution;|
| Placebo Comparator: Part B & A: 6-hour-Placebo<br>Part B, Placebo will be applied for 6 hours and removed. VP-102 is applied every 21 days for 4 treatments. | Combination Product: Placebo<br>* The placebo single-use applicator contains the same formulation as the VP-102 applicator but does not contain the active pharmaceutical ingredient cantharidin<br>|
| Active Comparator: Part B & A: VP-102 24-hour Active<br>For part A, VP-102 will be applied for 24 hours and removed. If 24 hours is selected as a dose regimen for Part B, VP-102 will be applied for 24 hours and removed. VP-102 is applied every 21 days for 4 treatments. | Combination Product: VP-102 and applicator<br>* In part A, VP-102 will be applied for either 2, 6 or 24 hours with each regimen compared to placebo. For part B, 2 of the regimens from part A will be chosen for Part B with each compared to Placebo. Only 4 arms are actually being studied.<br>* Other names: VP-102 (cantharidin) 0.7% w/v topical solution;|
| Placebo Comparator: Part B & A: 24-hour-Placebo<br>Part B, VP-Placebo will be applied for 24 hours and removed. VP-102 is applied every 21 days for 4 treatments. | Combination Product: Placebo<br>* The placebo single-use applicator contains the same formulation as the VP-102 applicator but does not contain the active pharmaceutical ingredient cantharidin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Subjects Exhibiting Complete Clearance of All Treatable Warts at the Study Day 84 (End of Treatment) Visit. | Proportion of subjects exhibiting complete clearance of all treatable warts (baseline and new) at the Study Day 84 EOT Visit. | Compares baseline wart count to Day 84, end of treatment. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Subjects Exhibiting Complete Clearance of All Treatable Warts (Baseline and New) at Treatment Visit 2, Treatment Visit 3, Treatment Visit 4, and Follow-up Visits on Study Day 112 and Study Day 147 (EOS) | Proportion of subjects exhibiting complete clearance of all treatable warts (baseline and new) at Treatment Visit 2, Treatment Visit 3, Treatment Visit 4, and Follow-up Visits on Study Day 112 and Study Day 147 (EOS). | Clearance compared from baseline to each study visit, treatment 2 (Day 21), 3 (Day 42), 4 (Day 63) and Day 84, 112 and 147. | 
| Proportion of Subjects Exhibiting 90% Clearance of All Treatable Warts (Baseline and New) at Treatment Visit 2, Treatment Visit 3, Treatment Visit 4, Study Day 84 (EOT), and Follow-up Visits on Study Day 112 and Study Day 147 (EOS) | Proportion of subjects exhibiting 90% clearance of all treatable warts (baseline and new) at Treatment Visit 2, Treatment Visit 3, Treatment Visit 4, Study Day 84 (EOT), and Follow-up Visits on Study Day 112 and Study Day 147 (EOS). | Compared from baseline to each study visit, treatment 2 (Day 21), 3 (Day 42), 4 (Day 63) and Day 84, 112 and 147. | 
| Proportion of Subjects Exhibiting 75% Clearance of All Treatable Warts (Baseline and New) at Treatment Visit 2, Treatment Visit 3, Treatment Visit 4, Study Day 84 (EOT), and Follow-up Visits on Study Day 112 and Study Day 147 (EOS) | Proportion of subjects exhibiting 75% clearance of all treatable warts (baseline and new) at Treatment Visit 2, Treatment Visit 3, Treatment Visit 4, Study Day 84 (EOT), and Follow-up Visits on Study Day 112 and Study Day 147 (EOS). | Compared from baseline to each study visit, treatment 2, (Day 21), 3 (Day 42), 4 (Day 63) and Day 84, 112 and 147. | 
| Change From Baseline in the Number of Treatable Warts (Baseline and New) at Treatment Visit 2, Treatment Visit 3, Treatment Visit 4, Study Day 84 (EOT), and Follow-up Visits on Study Day 112 and Study Day 147 (EOS) | Change from baseline in the number of treatable warts (baseline and new) at Treatment Visit 2, Treatment Visit 3, Treatment Visit 4, Study Day 84 (EOT), and Follow-up Visits on Study Day 112 and Study Day 147 (EOS). Number of warts present were recorded at each treatment visit as well as follow-up visits. For each post baseline treatment visit, the change in number of warts from baseline was calculated. | Compared from baseline to each study visit, treatment 2 (Day 21), 3 (Day 42), 4 (Day 63) and Day 84, 112 and 147. | 
| Percent Change From Baseline in the Number of Treatable Warts (Baseline and New) at Treatment Visit 2, Treatment Visit 3, Treatment Visit 4, at Study Day 84 (EOT), and Follow-up Visits on Study Day 112 and Study Day 147 (EOS) | Percent Change from Baseline in the Number of Treatable Warts (Baseline and New) at Treatment Visit 2, Treatment Visit 3, Treatment Visit 4, at Study Day 84 (EOT), and Follow-up Visits on Study Day 112 and Study Day 147 (EOS). | Percent change from baseline to each study visit, treatment 2 (Day 21), 3 (Day 42), 4 (Day 63) and Day 84, 112 and 147. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Human Papilloma Virus (HPV), Genital Warts, Sexually Transmitted Disease (STD), Viral Disease