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

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)

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.

Study Overview

• Status: Completed
• Conditions: Warts
• Intervention / Treatment: Biological: CANDIN; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 243
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Fort Smith, Arkansas, United States, 72916
      • Johnson Dermatology
    • Rogers, Arkansas, United States, 72758
      • Northwest Arkansas Clinical Trials Center PLLC
  • California
    • Encinitas, California, United States, 92024
      • California Dermatology and Clinical Research Institute
    • Newport Beach, California, United States, 92660
      • Silverberg MD Inc.
  • Massachusetts
    • Needham, Massachusetts, United States, 02492
      • Metro Boston Clinical Partners, LLC
    • Watertown, Massachusetts, United States, 02472
      • BayState Clinical Trials
  • Michigan
    • Fort Gratiot, Michigan, United States, 48059
      • Hamzavi Dermatology Clinical Trials
  • Minnesota
    • Fridley, Minnesota, United States, 55432
      • Minnesota Clinical Study Center
  • North Carolina
    • High Point, North Carolina, United States, 27262
      • Dermatology Consulting Services
  • Oregon
    • Portland, Oregon, United States, 97223
      • Oregon Medical Research Center
  • Texas
    • Austin, Texas, United States, 78759
      • DermResearch Inc.
    • Austin, Texas, United States, 78660
      • Austin Institute for Clinical Research Inc.
    • San Antonio, Texas, United States, 78218
      • Texas Dermatology and Laser Specialists
  • Utah
    • Salt Lake City, Utah, United States, 84117
      • Dermatology Research Center, Inc.
  • Virginia
    • Lynchburg, Virginia, United States, 24501
      • The Education and Research Foundation, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Men or women between the ages of 18 and 65 years inclusively at time of consent
2. Subjects presenting with 3 to 20 injectable common warts (verruca vulgaris) for at least 12 weeks at the time of the Baseline Visit
3. 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
4. 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

5. 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)
6. Mentally and legally capable of giving informed consent prior to any study related procedures

Exclusion Criteria:

1. 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
2. Subject has been diagnosed with diabetes mellitus
3. Subject has a history of keloid formation
4. 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
5. 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
6. 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
7. 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
8. Recalcitrant warts defined as those not successfully treated by 5 or more treatments (excluding OTC treatments)
9. Abnormal (low < 5 mm or high >25 mm) baseline result to the Delayed Type Hypersensitivity (DTH) test
10. Subject has a condition or treatment resulting in being immunocompromised
11. 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
12. 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)
13. Previous treatment of warts with any type of intralesional injection with candida extract (including CANDIN)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; 0.3 mL of CANDIN administered intralesionally in the largest common wart	Biological: CANDIN; Candida albicans Skin Test Antigen for Cellular Hypersensitivity
Experimental: Cohort 2; 0.5 mL of CANDIN administered intralesionally in the largest common wart	Biological: CANDIN; Candida albicans Skin Test Antigen for Cellular Hypersensitivity
Experimental: Cohort 3; 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; Candida albicans Skin Test Antigen for Cellular Hypersensitivity
Placebo Comparator: Pooled Placebo; 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; 0.9% Sodium Chloride Injection USP (non-preserved)

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Association Between the Age of the Largest Primary Injected Wart and Complete Resolution of the Largest Primary Injected Wart	Complete resolution of a wart was defined as the absence of visible or measurable presence of the wart	45 weeks
Association Between the Age of the Primary Injected Wart and the Recurrence of Any Resolved Wart at Any Visit.		45 weeks
Summary of Complete Resolution of the Largest Primary Wart and Type of Treatment History	Complete resolution of a wart was defined as the absence of visible or measurable presence of the wart	45 weeks
The Effect of the Treatment History on the Number of Recurrences of Resolved Primary Warts		45 weeks

Collaborators and Investigators

• Sponsor: Nielsen BioSciences, Inc.
• Investigators: Study Director: Thomas Carpenter, DVM, PhD, Nielsen BioSciences, Inc.

Publications and helpful links

General Publications

• Kim KH, Horn TD, Pharis J, Kincannon J, Jones R, O'Bryan K, Myers J, Nakagawa M. Phase 1 clinical trial of intralesional injection of Candida antigen for the treatment of warts. Arch Dermatol. 2010 Dec;146(12):1431-3. doi: 10.1001/archdermatol.2010.350. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2015
• Primary Completion (Actual): January 1, 2018
• Study Completion (Actual): March 1, 2018

Study Registration Dates

• First Submitted: March 13, 2015
• First Submitted That Met QC Criteria: March 18, 2015
• First Posted (Estimate): March 19, 2015

Study Record Updates

• Last Update Posted (Actual): June 4, 2019
• Last Update Submitted That Met QC Criteria: May 10, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: Common Warts; Verruca vulgaris
• Additional Relevant MeSH Terms: Skin Diseases; Virus Diseases; Infections; DNA Virus Infections; Skin Diseases, Infectious; Papillomavirus Infections; Skin Diseases, Viral; Tumor Virus Infections; Warts
• Other Study ID Numbers: CFW-2D