Evaluation of Systemic Exposure to VP-102 in Subjects With Molluscum Contagiosum.

This is a Phase 2, Open-Label Study to Evaluate the Safety, Efficacy and Systemic Exposure of VP-102 Topical Film Forming Solution \[0.7% (w/v) cantharidin\] in subjects 2 years and older with Molluscum Contagiosum. Up to 40 subjects will be enrolled in the study with the goal of 16 meeting criteria for, and completing all scheduled blood draws outlined in the exposure portion of the trial. Subjects that do not have enough molluscum lesions to participate in the exposure study but do meet all other criteria to participate in the study will be enrolled in the standard treatment group. No more than 16 subjects will complete exposure group activities; up to 16 subjects will be enrolled in the standard treatment group. The additional 8 subjects may be used for replacement patients. At least 3 patients in the exposure group will be from 2-5 years of age. All subjects will receive VP-102 containing 0.7% cantharidin to molluscum lesions every 21 days for a maximum of 4 sessions or until complete clearance.

In the exposure group, blood samples for systemic exposure evaluation will be collected on Day 1, prior to the drug application, and 2 (± 30 minutes), 6 (± 1 hour) and 24 (±3 hours) hours post-application. A dermatological examination will be performed by a qualified investigator quantifying molluscum lesion counts at every study visit.

• VP-102 with applicator (Combination product): Subjects will receive treatment to their molluscum contagiosum with VP-102.

Primary outcomes

• The Presence or Absence of Systemic Exposure to Cantharidin by the Collection and Analysis of Plasma Samples From Patients With 21 or More Molluscum Lesions Following Treatment of VP-102. [24 hours]: The primary objective is to determine any potential systemic exposure from a single 24-hour dermal application of VP-102 topical film-forming solution when applied to molluscum contagiosum (molluscum) lesions on pediatric subjects 2 years old and older.

Secondary outcomes

• Measurement of Efficacy - Complete Clearance [Baseline through EOS Day 84]: Proportion of subjects exhibiting complete clearance of all treated molluscum lesions (baseline and new) on or before Week 12 (EOS).

Other outcomes

• Proportion of Subjects Exhibiting a 90% or Greater Reduction of All Treated Molluscum Lesions (Baseline and New) at the EOS Visit. [Baseline to EOS Day 84]: Summaries of >=90% clearance by visit include clearance at that visit or any earlier visit (cumulative) baseline and ew at the EOS visit.
• Percent Reduction of Treated Molluscum Lesions From Baseline at the EOS Visit. [Baseline to EOS Day 84]: Percent reduction of treated molluscum lesions from Baseline Visit at the EOS visit.
• Change From Baseline in the Number of Treated Molluscum Lesions at the EOS Visit. [Baseline to EOS Day 84]: Molluscum Lesions- Change from Baseline visit in the number of treated molluscum lesions at the EOS Day 84 visit
• Change From Baseline in Quality of Life and Impact of Skin Disease as Measured by CDLQI Assessment [Baseline to EOS Day 84]: Change from Baseline in quality of life and impact of skin disease as measured by CDLQI assessment, Children's Dermatology Life Quality Index (CDLQI)- Composite Score The CDLQI was a 10-item questionnaire completed by subject/parent to assess skin condition over the previous week. From responses to that questionnaire, a composite score was calculated. The calculated composite score was the sum of the individual 10 items of the CDLQI and could range from 0-30. For each item on the CDLQI, a score of 0-3 was assigned using the following scores per response: * 3: Very much (or Prevented School, Question 7 only) * 2: Quite a lot * 1: Only a little * 0: Not at all
• Spread to Siblings as Measured by Any New Occurrence of Molluscum in Siblings of the Subject. [Baseline to EOS Day 84]: Spread of molluscum to siblings as measured by any new occurrence of molluscum in siblings of the subject.

Sex: All, ages: 2 Years to any, accepts healthy volunteers

Inclusion Criteria:

1. Be healthy subjects ages 2 years and older.
2. Patients with 1-20 lesions may be enrolled and treated in the standard treatment group but are not eligible for the exposure study.
3. Patients with 21 or more lesions may only be enrolled in the exposure group. Subjects participating in the Exposure group must have at least 21 lesions treated at Day 1 to qualify.
4. Be otherwise medically healthy with no clinically significant medical history as determined by the investigator. Patients exhibiting active Atopic Dermatitis may be enrolled.
5. Refrain from application of all topical agents including alcohol-based sanitary products and sunscreens for a minimum of 4 hours before Study drug application. Topical agents including alcohol-based sanitary products and sunscreens may be used after application of the study drug so long as they are not applied to or near treated skin.
6. Refrain from swimming, bathing or prolonged immersion in water until the Study drug is removed.
7. Have the ability or have a guardian able to follow study instructions and be likely to complete all study requirements.
8. Provide assent in a manner approved by the institutional review board (IRB) and have a parent/guardian provide written informed consent as evidenced by signature on IRB approved assent/consent forms.
9. Provide written authorization for use and disclosure of protected health information.
10. Agree to allow photographs of all selected lesions to be taken and/or send photos via text or email to the study team for assessment at 24 hours post treatment. Photos may be used as part of the study data and/or marketing package. (Photographs will be de-identified to those outside the research team. Effort will be made to ensure that no photos with identifiable features are obtained).

Exclusion Criteria:

1. Are unable to cooperate with the requirements or visits of the study, as determined by the investigator.
2. Have molluscum venereum (sexually transmitted molluscum).
3. Have active molluscum eczema.
4. Are systemically immunosuppressed or are receiving treatments such as chemotherapy or other non-topical immunosuppressive agents.
5. Have had any previous treatment of molluscum in the past 14 days including the use of cantharidin, antivirals, retinoids, curettage or freezing of lesions. Additional treatments for molluscum should not be implemented during the course of the study.
6. Have history of illness or any dermatologic disorder, which, in the opinion of the investigator will interfere with accurate counting of lesions or increase the risk of adverse events.
7. 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.
8. Have a history or presence of hypersensitivity or an idiosyncratic reaction to the Study drug or related compounds, or drug product excipients.
9. Have a condition or situation that may interfere significantly with the subject's participation in the study (e.g., patients 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.
10. Have received another investigational product within 14 days prior to the first application of the Study drug.
11. Have been treated within 14 days with a product that contains the active ingredient in VP-102 (topical or homeopathic preparations) for any reason prior to screening.
12. Are sexually active or may become sexually active and are unwilling to practice responsible birth control methods. Females that have reached menarche, must have a negative urine pregnancy test at screening and each visit prior to treatment with study medication.
13. Are pregnant or breastfeeding.

Participant flow

Outcome results

• The Presence or Absence of Systemic Exposure to Cantharidin by the Collection and Analysis of Plasma Samples From Patients With 21 or More Molluscum Lesions Following Treatment of VP-102. (Primary), Count of participants, Participants: Exposure Group 0
• Measurement of Efficacy - Complete Clearance (Secondary), Count of participants, Participants: Exposure Group 0; Standard Group 3
• Proportion of Subjects Exhibiting a 90% or Greater Reduction of All Treated Molluscum Lesions (Baseline and New) at the EOS Visit. (Other pre specified), Count of participants, Participants: Exposure Group 0; Standard Group 3
• Percent Reduction of Treated Molluscum Lesions From Baseline at the EOS Visit. (Other pre specified), Mean, percentage change from Baseline: Exposure Group -87.8 +/- 21.25; Standard Group -93.0 +/- 12.93
• Change From Baseline in the Number of Treated Molluscum Lesions at the EOS Visit. (Other pre specified), Mean, change in wart count: Exposure Group -39.3 +/- 21.98; Standard Group -10.7 +/- 6.16
• Change From Baseline in Quality of Life and Impact of Skin Disease as Measured by CDLQI Assessment (Other pre specified), Mean, units on a scale change from Baseline: Exposure Group 2.71 +/- 2.801; Standard Group 2.44 +/- 4.115
• Spread to Siblings as Measured by Any New Occurrence of Molluscum in Siblings of the Subject. (Other pre specified), Count of participants, Participants: Exposure Group 0; Standard Group 0

Adverse events

Time frame: Baseline to EOS Day 84

Other adverse events by term

• Results publication: Niazi S, Brabec B, Anschutz L, Willson C, Davidson M, Burnett P. A Phase 2 Open-Label Study to Evaluate VP-102 for the Treatment of Molluscum Contagiosum. J Drugs Dermatol. 2021 Jan 1;20(1):70-75. doi: 10.36849/JDD.5626. PMID 33400412

• Study Protocol (PDF, 2017-08-08)
• Statistical Analysis Plan (PDF, 2018-04-04)

• Gary Goldenberg, MD, Study director, Verrica Pharmaceuticals Inc.