Cantharidin and Occlusion in Verruca Epithelium (COVE-1)

• ClinicalTrials.gov Identifier: NCT03487549
• Recruitment Status: Completed
• First Posted: April 4, 2018
• Results First Posted: September 1, 2021
• Last Update Posted: September 1, 2021
• Sponsor: Verrica Pharmaceuticals Inc.
• Collaborators: Instat Consulting, Inc.; Paidion Research, Inc.; BioClinica, Inc.; ALMAC Clinical Services
• Information provided by (Responsible Party): Verrica Pharmaceuticals Inc.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
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	Combination Product: VP-102 Cantharidin topical film forming solution; Combination Product: VP-102 Cantharidin, topical film forming solution	Phase 2

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 56 participants
• Allocation: N/A
• Intervention Model: Sequential Assignment
• Intervention 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)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Open Label Study to Evaluate the Efficacy, Safety and Tolerability of VP-102 in Subjects With Common Warts (Verruca Vulgaris)
• Actual Study Start Date: March 27, 2018
• Actual Primary Completion Date: May 16, 2019
• Actual Study Completion Date: July 15, 2019

Arms and Interventions

Arm

Intervention/treatment

Experimental: VP-102; Open label of VP-102 cantharidin topical film forming solution, using the VP-102 applicator.

Combination Product: VP-102 Cantharidin topical film forming solution; 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.; Other Name: VP-102-Cantharidin, film forming solution, VP-102 - Cohort 1; Combination Product: VP-102 Cantharidin, topical film forming solution; 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.; Other Name: VP-102 Cantharidin, film forming solution, VP-102 - Cohort 2

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Cohort 1: Change From Baseline in the Number of Treatable Warts (Baseline and New) at the EOS Visit (Day 84) [ Time Frame: Change in the number of warts compared at Baseline (Visit 1) to the End of Study Visit (Day 84). ]
   Cohort 1: Change from baseline in the number of treatable warts (baseline and new) at the EOS Visit (Day 84).
2. Cohort 1: Percent Change From Baseline in the Number of Treatable Warts (Baseline and New) at the EOT Visit (Day 84). [ Time Frame: Baseline (Visit 1) to End of Treatment 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).
3. 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 [ Time Frame: Baseline, Day 14, 28, 42 and 84 (EOS) ]
   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.
4. Cohort 2: Change From Baseline in the Number of Treatable Warts (Baseline and New) at the EOT Visit Day 84) [ Time Frame: Baseline, Day 84 (EOS) ]
   Cohort 2: Change from baseline in the number of treatable warts (baseline and new) at the EOT Visit Day 84).
5. Cohort 2: Change From Baseline in the Percent of Treatable Warts (Baseline and New) at the EOT Visit (Day 84) [ Time Frame: Baseline (Visit 1) to End of Treatment Visit (Day 84). ]
   Cohort 2: Change from baseline in the percent of treatable warts (baseline and new) at the EOT Visit (Day 84).
6. 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 [ Time Frame: Baseline, Day 21, 42, 63, and 84 (EOS), 105, 126, and 147 ]
   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.

Other Outcome Measures:

1. Cohort 1:Percent Reduction of All Treatable Warts (Baseline and New) From Baseline at Visit 2, Visit 3, Visit 4 and Over the Duration of the Study. [ Time Frame: Baseline, Day 14, 28, 42, and 84 (EOS) ]
   Cohort 1: Percent change from baseline in the number of treatable warts (Baseline and new) from Baseline at Visit 2, Visit 3, Visit 4 and over the duration of the study.
2. Cohort 1: Change From Baseline in the Number of Treatable Warts (Baseline and New) at Visit 2, Visit 3, Visit 4 and the EOS Visit [ Time Frame: Baseline, Day 14, 28, 42, and 84 (EOS) ]
   Cohort 1: Change from baseline in the number of treatable warts (baseline and new) at Visit 2, Visit 3, Visit 4 and the EOS Visit.
3. Cohort 1: Proportion of Subjects Exhibiting ≥ 50% Clearance of All Treatable Warts (Baseline and New) at the EOS Visit as Compared to Baseline [ Time Frame: Compare Treatment Visit 1 (Baseline) to End of Study (Day 84). ]
   Cohort 1: Proportion of subjects exhibiting ≥ 50% clearance of all treatable warts (baseline and new) at the EOS visit as compared to baseline.
4. Cohort 1-Proportion of Subjects Who Respond to Treatment Defined by a ≥ 50% Reduction in Total Wart Area at EOS Compared to Baseline [ Time Frame: Baseline, Day 14, 28, 42, and 84 (EOS) ]
   Cohort 1-Proportion of subjects who respond to treatment defined by a ≥ 50% reduction in total wart area at EOS compared to baseline.
5. Cohort 1-Proportion of Subjects Exhibiting Reduction of at Least 1 Treatable Wart From Baseline at Visit 2, Visit 3, Visit 4 and at the EOS Visit (Day 84) [ Time Frame: Baseline, Day 14, 28, 42, and 84 (EOS) ]
   Cohort 1-Proportion of subjects exhibiting reduction of at least 1 treatable wart from baseline at Visit 2, Visit 3, Visit 4 and at the EOS Visit (Day 84).
6. Cohort 2: Percent Reduction of All Treatable Warts (Baseline and New) From Baseline at Visit 2, Visit 3, Visit 4 and Over Duration of the Study. [ Time Frame: Baseline to Treatment Visits 2 (Day 21), 3 (Day 42), 4 (Day 63) through the End of Treatment (Day 84). ]
   Cohort 2: Intent to Treat population Cohort 2-Percent reduction of all treatable warts (baseline and new) from baseline at Visit 2, Visit 3, Visit 4 and over duration of the study.
7. Cohort 2: Change From Baseline in the Number of Treatable Warts (Baseline and New) at Treatment Visit 2, Treatment Visit 3, Treatment Visit 4 and the EOT Visit (Day 84) [ Time Frame: Baseline, Day 14, 28, 42, and 84 (EOS) ]
   Cohort 2: Change from baseline in the number of treatable warts (baseline and new) at Treatment Visit 2, Treatment Visit 3, Treatment Visit 4 and the EOT Visit (Day 84).
8. Cohort 2: Proportion of Subjects Exhibiting ≥ 50 % Clearance of All Treatable Warts (Baseline and New) at the EOT Visit (Day 84) as Compared to Baseline [ Time Frame: Baseline to Day 84 (EOT) ]
   Cohort 2: Proportion of subjects exhibiting ≥ 50 % clearance of all treatable warts (baseline and new) at the EOT Visit (Day 84) as compared to baseline.
9. Cohort 2: Proportion of Subjects Who Respond to Treatment Defined by a ≥ 50% Reduction in Total Wart Area at EOT Compared to Baseline [ Time Frame: Baseline to EOT (Day 84) ]
   Cohort 2: Proportion of subjects who respond to treatment defined by a ≥ 50% reduction in total wart area at EOT compared to baseline.
10. Cohort 2: Proportion of Subjects Exhibiting Reduction of at Least 1 Treatable Wart From Baseline at Visit 2, Visit 3, Visit 4 and at the EOT Visit (Day 84) [ Time Frame: Baseline, Day 14, 28, 42, and 84 (EOS) ]
    Cohort 2: Proportion of subjects exhibiting reduction of at least 1 treatable wart from baseline at Visit 2, Visit 3, Visit 4 and at the EOT Visit (Day 84).
11. Cohort 2: Proportion of Subjects Exhibiting Complete Clearance of All Treatable Warts (Baseline and New) at Follow-up Visits on Day 105, Day 126 and Day 147 [ Time Frame: Treatment Visit 1 (Baseline) to each follow-up visit Day 105, Day 126 and Day 147. ]
    Cohort 2: Proportion of subjects exhibiting complete clearance of all treatable warts (baseline and new) at follow-up visits on Day 105, Day 126 and Day 147.
12. Cohort 2: Percent Reduction of All Treatable Warts (Baseline and New) From Baseline at Follow-up Visits on Day 105, Day 126 and Day 147 [ Time Frame: Baseline to follow-up visits on Day 105, Day 126 and Day 147 ]
    Cohort 2: Percent reduction of all treatable warts (baseline and new) from baseline at follow-up visits on Day 105, Day 126 and Day 147.
13. Cohort 2: Change From Baseline in the Number of Treatable Warts (Baseline and New) at Follow-up Visits on Day 105, Day 126 and Day 147 [ Time Frame: baseline to Day 105, Day 126 and Day 147 ]
    Cohort 2: Change from baseline in the number of treatable warts (baseline and new) at follow-up visits on Day 105, Day 126 and Day 147.

Eligibility Criteria

• Ages Eligible for Study: 2 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. 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.
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).
3. 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) .
4. Have warts that have been present for at least 4 weeks at the time of the baseline visit.
5. Consent to having all warts treated (the physician must also be willing to treat all warts initially present).
6. Be otherwise medically healthy with no clinically significant medical history, physical examination or vital signs as determined by the investigator.
7. 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.
8. Refrain from swimming, bathing or prolonged immersion in water or any liquids until the Study drug is removed.
9. Have the ability, or have a guardian with the ability, to follow study instructions and be likely to complete all study requirements.
10. Agree to use no wart-removing product (prescription or over-the-counter [OTC]) other than the Study drug during the course of the study.
11. 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.
12. Provide written authorization for use and disclosure of protected health information.
13. 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:

1. Are unable to cooperate with the requirements or visits of the study, as determined by the investigator.
2. 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)
3. 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.
4. Have more than 6 common warts at baseline.
5. 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.
6. 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.
7. 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.
8. Have been treated within 14 days with a product that contains cantharidin (topical or homeopathic preparations) for any reason prior to screening.
9. Have received another investigational product as part of a clinical trial within 30 days prior to the first application of the Study drug.
10. Currently have or have a history of epidermodysplasia verruciformis.
11. 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.
12. Have an active malignancy or are undergoing treatment for any malignancy.
13. 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.
14. 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).
15. 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.
16. 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.
17. Are pregnant or breastfeeding.

Contacts and Locations

Locations

United States, Arkansas

Cohort 2: Applied Research Center of Arkansas

Little Rock, Arkansas, United States, 72212

United States, Florida

Cohort 2: Solutions Through Advanced Research

Jacksonville, Florida, United States, 32256

United States, Indiana

Cohort 2: The Indiana Clinical Trials Center

Plainfield, Indiana, United States, 46168

United States, Michigan

Cohort 2: Clarkston Skin Research

Clarkston, Michigan, United States, 48346

United States, North Carolina

Cohort 1-Wake Research Associates

Raleigh, North Carolina, United States, 27612

Sponsors and Collaborators

Verrica Pharmaceuticals Inc.

Instat Consulting, Inc.

Paidion Research, Inc.

BioClinica, Inc.

ALMAC Clinical Services

Investigators

• Principal Investigator: Adnan Nasir, MD; Cohort 1: Wake Dermatology
• Principal Investigator: Scott Guenthner, MD; Cohort 2: Indiana Clinical Trials Center

  Study Documents (Full-Text)

Documents provided by Verrica Pharmaceuticals Inc.:

Study Protocol  [PDF] November 1, 2018

Statistical Analysis Plan  [PDF] July 25, 2019

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Guenthner S, McFalda W, Kwong P, Eads K, McCafferty M, Rieger J, Glover DK, Willson C, Burnett P, Olivadoti M. COVE-1: A Phase 2, Open-Label Study to Evaluate Efficacy and Safety and the Optimal Regimen of VP-102, a Proprietary Drug-Device Product Containing Topical Cantharidin (0.7% w/v) Under Occlusion for the Treatment of Common Warts. Dermatol Ther (Heidelb). 2021 Oct;11(5):1623-1634. doi: 10.1007/s13555-021-00576-y. Epub 2021 Jul 21.

• Responsible Party: Verrica Pharmaceuticals Inc.
• ClinicalTrials.gov Identifier: NCT03487549
• Other Study ID Numbers: VP-102-105
• First Posted: April 4, 2018
• Results First Posted: September 1, 2021
• Last Update Posted: September 1, 2021
• Last Verified: August 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes
• Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:

Infections; Communicable Diseases; Virus Diseases; Warts; Papillomavirus Infections; Skin Diseases, Infectious; DNA Virus Infections; Tumor Virus Infections; Skin Diseases, Viral; Skin Diseases; Disease Attributes; Pathologic Processes; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Genital Diseases; Urogenital Diseases; Pharmaceutical Solutions; Cantharidin; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action