A Phase 2 Open-Label Study to Evaluate VP-102 for the Treatment of Molluscum Contagiosum

January 2021 | Volume 20 | Issue 1 | Original Article | 70 | Copyright © January 2021


Published online December 21, 2020

Sahra Niazi MDa,b, Bradford Brabec MDa,b, Luke Anschutz MDa,b, Cynthia Willson RN BSNc, Matthew Davidson PhDc, Patrick Burnett MD PhDc

aComplete Children’s Health, Pediatrics, Lincoln, NE
bMidwest Children’s Health Research Institute, Lincoln, NE
cVerrica Pharmaceuticals Inc., West Chester, PA

effective in large-scale clinical trials.7 While some clinicians may choose not to treat and rely on spontaneous resolution of lesions, there is a growing body of literature in support of active treatment.4,7,8 In a survey of 95 pediatric dermatologists, compounded cantharidin was identified as one of the most frequently used approaches and 92% of respondents were satisfied with the efficacy of this agent.9

Cantharidin is a terpenoid blistering agent secreted from many species of blister beetles (family Meloidae, Lytta vesicatoria). It has been used in Eastern medicine for 2000 years and has been documented as a treatment for MC and verrucae vulgaris in the US since the 1950s.10 Once applied, acantholysis occurs through detachment of the desmosomes from tonofilaments, followed by formation of a superficial blister.11

Although normally used topically, compounded cantharidin has shown toxic effects following oral ingestion including ulceration of the gastrointestinal and genitourinary tracts, and electrolyte and renal function disturbance in humans (LD50 is 0.0.3–0.5 mg/kg). While systemic toxicity is not expected with topical cantharidin, systemic exposure studies have yet to be completed. Several small retrospective and prospective clinical studies using compounded cantharidin formulations have demonstrated effectiveness in subjects with MC using a variety of application durations and dosing regimens.12-15

There are caveats to consider when using cantharidin. Changes in concentration can occur with compounded formulations when exposed to air. Raw cantharidin and its formulations differ based on the source of the active ingredient, formulation components, or methods used by the pharmacy compounding the drug. The formulation is commonly applied using rudimentary tools (eg, cotton-tipped wooden swabs or toothpicks), which can lead to unintended side effects, treating of unaffected skin, and cross-contamination.16 These inconsistencies in source material, formulations, and methods of application, along with the lack of large-scale randomized controlled trials, result in a lack of robust evidence in support of cantharidin as a treatment for MC.16

Herein we report the results of an open-label Phase 2 clinical study utilizing VP-102, a proprietary, drug-device combination product containing a topical formulation of 0.7% (w/v) cantharidin administered with a single-use applicator device for the treatment of MC in pediatric subjects. The standardized drug formulation and precision applicator combination of VP-102, with an established application duration and dosing schedule, were designed to overcome the limitations of compounded cantharidin formulation and application concerns.

Pharmacokinetic testing of blood samples was completed to evaluate the systemic exposure of cantharidin in pediatric subjects who had higher lesion counts (≥21 lesions). QoL was assessed using the Children’s Dermatology Quality of Life Index (CDLQI) to determine the impact of the disease at baseline and after treatment with VP-102.

METHODS

Study Subjects and Treatment Procedures
The Phase 2, single-site, open-label study evaluated the potential systemic exposure, safety, and efficacy of topical application of VP-102 in children 2–15 years of age. The study was registered in the US (NCT03186378). Eligible participants with MC were enrolled. All subjects participated in the protocol as outlined below, with a subset of subjects with 21 or more MC lesions at baseline undergoing blood sampling for systemic exposure (exposure group). Any subject in the exposure group who did not complete all blood draws could continue to receive treatment but could be replaced. The protocol and consent forms were approved by an independent ethics committee. Assent and written informed consent were obtained from subjects or their parents/guardians.

VP-102 Treatment Methods
The study included a screening period of up to 14 days for an eligibility assessment. Physical exams, medical histories, and MC lesion counts were completed prior to treatment. Washout of any prior MC treatment agent occurred before the first treatment application on day 1. Additional applications of VP-102 to all treatable (baseline and new) lesions were completed once every 21 days (days 21, 42, 63) if lesions were present, for a maximum of four applications. No more than two applicators were permitted per subject per treatment. The subject or their parent/guardian was instructed to wash off the study drug 24 hours after treatment, or earlier, if significant blistering or pain occurred. The EOS assessments of complete clearance and safety were completed on day 84 or, in the case of subjects achieving complete clearance on or before Treatment 4, at the same visit at which subjects exhibited complete clearance. For subjects with complete clearance prior to Treatment 4, no further visits were required.

Subjects in the exposure group were required to have ≥21 lesions, and at least 3 subjects were required to be between 2 and 5 years of age. MC lesions were treated in all anatomical areas at the discretion of the investigator in the interest of subject safety.

Systemic Exposure Methods (Exposure Group)
Blood was collected prior to the first application of VP-102 on day 1 and then at 2 (± 30 min), 6 (± 1 hr), and 24 (± 3 hrs) hours thereafter, for a total of 4 blood samples (2 mL each). No samples were collected at other treatment visits. The presence of cantharidin in plasma was determined by a GLP-compliant independent laboratory (Pacific BioLabs, Hercules, CA) using a validated gas chromatography/mass spectrometry analytical