Cantharidin and Occlusion in Verruca Epithelium

Study Overview
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Brief Summary
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This is a Phase 2, open label study (Study number VP-102-105; referred to as COVE-1 [Cantharidin and Occlusion in Verruca Epithelium]) to evaluate the efficacy, safety and tolerability of VP-102 treatment in subjects with common warts. This study has two Cohorts.

Detailed Description
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The first Cohort (Cohort 1) utilizes a treatment interval of at least 14 days between treatments with longer treatment intervals being allowed depending on a specific patient's clinical response.Twenty Subjects (2 years and older) are targeted completing End of Study (EOS) visit in Cohort 1. The second Cohort (Cohort 2) utilizes a treatment interval of 21 days between treatments. Paring of lesions is allowed. Approximately 35 subjects (12 years and older) will be enrolled in Cohort 2. Up to 4 sites will participate in the study.

Official Title
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A Phase 2, Open Label Study to Evaluate the Efficacy, Safety and Tolerability of VP-102 in Subjects With Common Warts (Verruca Vulgaris)

Conditions
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Common Wart, Warts Hand, Warts, Papillomavirus Infections, DNA Virus Infections, Skin Diseases, Viral, Skin Diseases, Infectious, Skin Diseases, Virus Diseases, Tumor Virus Infections, Verruca Vulgaris, Verruca

Intervention / Treatment
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* Combination Product: VP-102 Cantharidin topical film forming solution
* Combination Product: VP-102 Cantharidin, topical film forming solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be healthy, immunocompetent males or females at least 2 years of age and older for Cohort 1 and 12 years of age and older for Cohort 2. Present with 1-6 common warts (verruca vulgaris) located anywhere on the body except for the following prohibited areas: the eye area (including eyelids), lips, oral cavity, nasal cavity, inside of the ears, palms of the hands, volar surface of the fingers or toes, under the finger nails (near and on the sides of the nails is allowed for Cohort 1, but warts near and on the sides of the nail (e.g., periungual) are not allowed in Cohort 2), soles of the feet, or the anogenital area. (Warts within 10 mm of a mucosal surface should not be treated). Have warts that are ≤10 mm in diameter and ≤3 mm in height. (Subjects with warts that are adjacent, touching or clustered may be included so long as the combined diameter in the longest direction does not exceed 10 mm. Individual lesions that are adjacent, touching or clustered should be counted as distinct lesions for the purposes of tracking, inclusion and clearance)(subjects in Cohort 2 can be pared, when necessary and appropriate, prior to evaluating height eligibility) . Have warts that have been present for at least 4 weeks at the time of the baseline visit. Consent to having all warts treated (the physician must also be willing to treat all warts initially present). Be otherwise medically healthy with no clinically significant medical history, physical examination or vital signs as determined by the investigator. Be free of any systemic or dermatologic disorder, which, in the opinion of the investigator, will interfere with the study results or increase the risk of Aes. Refrain from swimming, bathing or prolonged immersion in water or any liquids until the Study drug is removed. Have the ability, or have a guardian with the ability, to follow study instructions and be likely to complete all study requirements. Agree to use no wart-removing product (prescription or over-the-counter [OTC]) other than the Study drug during the course of the study. Provide written informed consent or assent in a manner approved by the institutional review board (IRB) and/or have a parent/guardian provide written informed consent as evidenced by the signature on an IRB approved assent/consent form. Provide written authorization for use and disclosure of protected health information. If participating in the optional photographic portion of the study, agree to allow photographs of warts to be taken at each Treatment Visit by the research team and agree to share photos taken at home with the research team via text, email or in-person upload. Exclusion Criteria: Are unable to cooperate with the requirements or visits of the study, as determined by the investigator. Are systemically immunosuppressed or have required, or will require, systemic immunosuppressive or immunomodulatory medication (including oral or parenteral corticosteroids) within 30 days prior to enrollment or during the course of the study. (Routine use of inhaled or intranasal corticosteroids during the study is allowed) Have any chronic or acute medical condition that, in the opinion of the investigator, may interfere with the study results or place the subject at undue risk. (e.g., human immunodeficiency virus, systemic lupus erythematosus, viral hepatitis, uncontrolled diabetes). NOTE: Immunizations and flu shots may be administered throughout the study, but not within 5 days before or after treatment. Have more than 6 common warts at baseline. Present with any verruca plana, mosaiform, filiform, subungual (under the nail), genital or anal warts. In Cohort 2, subjects with periungual warts are also excluded. Have any warts present at baseline in an anatomic location that the subject, parent/guardian or the physician is unwilling to treat or are located in an area that cannot be easily occluded with tape. Have had any previous treatment of common warts including, but not limited to, the use of cantharidin, antivirals, retinoids, salicylic acid, lactic acid, hydrogen peroxide, candida antigen, diphencyprone, dinitrochlorobenzene, sandalwood oil, thuja oil, squaric acid dibutyl ester, povidone iodine, nitric oxide, curettage or freezing of warts in the past 14 days. In addition, these treatments or any other over-the-counter wart treatment should not be implemented during the course of the study. Have been treated within 14 days with a product that contains cantharidin (topical or homeopathic preparations) for any reason prior to screening. Have received another investigational product as part of a clinical trial within 30 days prior to the first application of the Study drug. Currently have or have a history of epidermodysplasia verruciformis. Have a history of illness or any dermatologic disorder, which, in the opinion of the investigator, will interfere with accurate assessment of the warts or increase the risk of adverse events. Have an active malignancy or are undergoing treatment for any malignancy. Have a history or presence of clinically significant medical, psychiatric, or emotional condition or abnormality that, in the opinion of the investigator, would compromise the safety of the subject or the quality of the data. Have a history or presence of hypersensitivity or an idiosyncratic reaction to the Study drug or related compounds, or drug product excipients (acetone, ethyl alcohol, nitrocellulose, hydroxypropyl cellulose, castor oil, camphor, gentian violet, and denatonium benzoate). Have a condition or situation that may interfere significantly with the subject's participation in the study (e.g., subjects who required hospitalization in the 2 months prior to screening for an acute or chronic condition including alcohol or drug abuse), at the discretion of the investigator. Are sexually active or may become sexually active and are unwilling to practice responsible birth control methods. (e.g., combination of condoms and foam, birth control pills, intrauterine device, patch, shot and vaginal ring, etc.). Withdrawal is not an acceptable method of birth control. Females that have reached menarche must have a negative urine pregnancy test at each visit prior to treatment with Study drug. Are pregnant or breastfeeding.

Ages Eligible for Study
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Minimum Age: 2 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
Intervention Model: Sequential Assignment
Interventional Model Description: This study has 2 cohorts. Cohort 1 of the study enrolled 21 subjects and has completed all subject related study activities. Analysis is to be conducted at Day 84. Cohort 2 will utilize 4 sites with an enrollment of approximately 35 subjects. The primary analysis will be conducted at Day 84 with an additional period of follow up out to Day 147.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VP-102<br>Open label of VP-102 cantharidin topical film forming solution, using the VP-102 applicator. | Combination Product: VP-102 Cantharidin topical film forming solution<br>* VP-102, a single-use drug device combination product containing (cantharidin) topical solution, 0.7% (w/v). Treatment interval of at least 14 days between treatments.<br>* Other names: VP-102-Cantharidin, film forming solution, VP-102 - Cohort 1;Combination Product: VP-102 Cantharidin, topical film forming solution<br>* VP-102, a single-use drug device combination product containing (cantharidin) topical solution, 0.7% (w/v). Treatment interval of at least 21 days between treatments.<br>* Other names: VP-102 Cantharidin, film forming solution, VP-102 - Cohort 2;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohort 1: Proportion of Subjects Exhibiting Complete Clearance of All Treatable Warts (Baseline and New) at the EOS Visit (Day 84) | Cohort 1: Proportion of subjects exhibiting complete clearance of all treatable warts (baseline and new) at the EOS Visit (Day 84). | Treatment Visit Day 1 (Baseline) compared to Day 84 (EOS) Visit. | 
| Cohort 2: Proportion of Subjects Exhibiting Complete Clearance of All Treatable Warts (Baseline and New) at the EOT Visit (Day 84) | Cohort 2: Proportion of subjects exhibiting complete clearance of all treatable warts (baseline and new) at the EOT Visit (Day 84). | Compare Treatment Visit 1 (Baseline) to EOT Visit (Day 84) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohort 1: Change From Baseline in the Number of Treatable Warts (Baseline and New) at the EOS Visit (Day 84) | Cohort 1: Change from baseline in the number of treatable warts (baseline and new) at the EOS Visit (Day 84). | Change in the number of warts compared at Baseline (Visit 1) to the End of Study Visit (Day 84). | 
| Cohort 1: Percent Change From Baseline in the Number of Treatable Warts (Baseline and New) at the EOT Visit (Day 84). | Cohort 1: Assessing the percent change from Baseline in the number of treatable warts (Baseline and new) at the EOT visit (Day 84). | Baseline (Visit 1) to End of Treatment Visit (Day 84). | 
| Cohort 1: Proportion of Subjects Exhibiting Complete Clearance of All Treatable Warts (Baseline and New) at Visit 2, Visit 3, Visit 4 and Over the Duration of the Study | Cohort 1: Proportion of subjects exhibiting complete clearance of all treatable warts (baseline and new) at Visit 2, Visit 3, Visit 4 and over the duration of the study. | Baseline, Day 14, 28, 42 and 84 (EOS) | 
| Cohort 2: Change From Baseline in the Number of Treatable Warts (Baseline and New) at the EOT Visit Day 84) | Cohort 2: Change from baseline in the number of treatable warts (baseline and new) at the EOT Visit Day 84). | Baseline, Day 84 (EOS) | 
| Cohort 2: Change From Baseline in the Percent of Treatable Warts (Baseline and New) at the EOT Visit (Day 84) | Cohort 2: Change from baseline in the percent of treatable warts (baseline and new) at the EOT Visit (Day 84). | Baseline (Visit 1) to End of Treatment Visit (Day 84). | 
| Cohort 2: Proportion of Subjects Exhibiting Complete Clearance of All Treatable Warts, (Baseline and New), at Visit 2, Visit 3, Visit 4 and Over the Duration of the Study | Cohort 2: Proportion of subjects exhibiting complete clearance of all treatable warts, (baseline and new), at Visit 2, Visit 3, Visit 4 and over the duration of the study. | Baseline, Day 21, 42, 63, and 84 (EOS), 105, 126, and 147 |