Safety and Efficacy of Varying Regimens of CANDIN for Treatment of Common Warts (Verruca Vulgaris)

Study Overview
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Brief Summary
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This is a placebo-controlled, double-blind (subject, Investigator, and site staff with the exception of unblinded dedicated staff to handle study medication), phase 2a study with 3 dose cohorts, randomized (concealed) to CANDIN or placebo (3:1). Main study will be up to 20 weeks (10 doses administered every other week) or until a subject has complete resolution of all injectable common warts. Subjects who cannot tolerate dosing every 2 weeks due to a local tolerance issue may be injected at 3-week intervals for up to 10 doses, increasing the length of the study to 29 weeks. Subjects will be followed for 4 months after final injection(s) for evidence of new or reoccurring warts and for safety evaluation.

Official Title
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A Phase IIa, Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Efficacy of Varying Regimens of CANDIN for Treatment of Common Warts (Verruca Vulgaris)

Conditions
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Warts

Intervention / Treatment
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* Biological: CANDIN
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men or women between the ages of 18 and 65 years inclusively at time of consent Subjects presenting with 3 to 20 injectable common warts (verruca vulgaris) for at least 12 weeks at the time of the Baseline Visit Subject's common warts for injection must measure between 3 and 20 mm at Baseline Visit and be located on hands, feet (excluding soles), limbs, and/or trunk. Flat, plantar, facial, periungual, genital warts or warts in region of pre-existing inflammatory condition are excluded from injection Subjects enrolled into Cohort 3 must have common warts for injection in at least 2 different anatomical regions defined as: left arm, right arm, left hand, right hand, left leg, right leg, left foot (excluding sole), right foot (excluding sole) and torso Subject, male or female is willing to use effective contraceptive method for at least 30 days before the Baseline Visit and at least 30 days after the last study drug administration unless not of childbearing potential as defined as post-menopausal for at least 2 years (females) or surgically sterile (tubal ligation, oophorectomy, or hysterectomy for females, and vasectomy for males). The only contraceptive use exceptions would be individuals in exclusive same sex partnerships and individuals who agree to remain non-sexually active for the duration of the study. Acceptable contraceptive methods for subjects include: Barrier methods, such as condom, sponge or diaphragm, combined with spermicide in foam, gel or cream; Hormonal contraception (oral, intramuscular, implant or transdermal which includes Depo-Provera, Evra and Nuvaring); Intrauterine device (IUD) Mentally and legally capable of giving informed consent prior to any study related procedures Exclusion Criteria: Presence of systemic or localized diseases, conditions, or medications that could interfere with assessment of safety and efficacy or that compromise immune function including psoriasis Subject has been diagnosed with diabetes mellitus Subject has a history of keloid formation Injectable common wart(s) located in areas with existing dermatologic conditions (such as psoriasis) or with an underlying inflammatory conditions (such as arthritic joints), or tattoos or implants/piercing/hardware or marking that may conceal responses or reactions are excluded from injection Existing/planned pregnancy, childbirth in the past six months prior to the Baseline Visit, or breast feeding, or plan on donating eggs or sperm during the study and in the month following the last injection Treatment of warts with liquid nitrogen, carbon dioxide, electrodessication, laser, surgery, simple occlusion (e.g. duct tape) salicylic or related acids, OTC treatments, cantharidin, or other treatments within 4 weeks of the Baseline Visit Treatment with immunotherapy (DPCP, DNCB or other), imiquimod, 5-fluorouracil, bleomycin, podophyllin or any other wart immunotherapy or treatment designed to stimulate immune response (except for treatments already listed in exclusion criterion 6) within 12 weeks of the Baseline Visit Recalcitrant warts defined as those not successfully treated by 5 or more treatments (excluding OTC treatments) Abnormal (low < 5 mm or high >25 mm) baseline result to the Delayed Type Hypersensitivity (DTH) test Subject has a condition or treatment resulting in being immunocompromised Systemic treatment (such as oral or injected) with cimetidine, zinc supplements at a dose higher than 20 mg of elemental zinc daily or an immunosuppressive drug (such as: azathioprine, 6-mercaptopurine, methotrexate, infliximab, adalimumab, etanercept, systemic steroids, etc.) within 12 weeks of the Baseline Visit Subject has used any investigational agent within 30 days prior to the Baseline Visit or within 5 half-lives of that investigational agent prior to the Baseline Visit (whichever is longer) Previous treatment of warts with any type of intralesional injection with candida extract (including CANDIN)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>0.3 mL of CANDIN administered intralesionally in the largest common wart | Biological: CANDIN<br>* Candida albicans Skin Test Antigen for Cellular Hypersensitivity<br>|
| Experimental: Cohort 2<br>0.5 mL of CANDIN administered intralesionally in the largest common wart | Biological: CANDIN<br>* Candida albicans Skin Test Antigen for Cellular Hypersensitivity<br>|
| Experimental: Cohort 3<br>0.3 mL of CANDIN administered intralesionally in up to 4 warts at the same visit (up to 1.2 mL total injected volume) | Biological: CANDIN<br>* Candida albicans Skin Test Antigen for Cellular Hypersensitivity<br>|
| Placebo Comparator: Pooled Placebo<br>0.3 mL or 0.5 mL administered intralesionally in the largest common wart, or 0.3 mL administered intralesionally in up to 4 warts at the same visit (up to 1.2 mL total injected volume) | Other: Placebo<br>* 0.9% Sodium Chloride Injection USP (non-preserved)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Complete Resolution of a Primary Injected Wart(s) at Any Treatment or Follow-up Visit | Complete resolution of a wart was defined as the absence of visible or measurable presence of the wart | 45 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With a Complete Resolution of All Common Warts at Any Treatment or Follow-up Visit | Complete resolution of a wart was defined as the absence of visible or measurable presence of the wart | 45 weeks | 
| Number of Subjects With Complete Resolution of Primary Injected Wart(s) at the 4 Month Follow-up Visit | Complete resolution of a wart was defined as the absence of visible or measurable presence of the wart | 4 month follow up visit at 45 weeks | 
| Number of Injection Visits Needed to Obtain Complete Resolution of the Primary Injected Wart(s) | Complete resolution of a wart was defined as the absence of visible or measurable presence of the wart | 45 weeks | 
| Number of Injection Visits for >50% Reduction in Area of the Primary Injected Wart(s) |  | 45 weeks | 
| Number of Injection Visits to >50% Reduction in the Total Area of All Measured Warts |  | 45 weeks | 
| Number of Subjects With Scarring at the Site of Resolved Primary and Non-primary Injected Wart(s) | Scarring at any visit, many reports were transient being noted at only one or two visits and noted as resolving during the course of the study | 45 weeks | 
| Number of Subjects With Hypopigmentation at the Site of Resolved Primary and Non-primary Injected Wart(s) |  | 45 weeks | 
| Number of Subjects With Injection Site Reactions With Frequency Greater Than 5% |  | 45 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Verruca vulgaris, Common Warts