Phase II, Double-Blind, Vehicle-Controlled Study to Determine the Cantharidin Dose Regimen, Efficacy, Safety, and Tolerability of VP-102 in Subjects with External Genital Warts

Abstract

Background: External genital warts are caused by various subtypes of the human papilloma virus and spread through direct skin-to-skin contact. Approximately 1% of the US population have external genital warts. Although cantharidin has been used to treat external genital warts for decades, there are no US Food and Drug Administration-approved cantharidin products and no reliable or controlled sources of cantharidin available. VP-102 is a drug-device combination product containing cantharidin (0.7% w/v) in a single-use shelf-stable applicator.

Objective: The objective of this randomized, double-blind, vehicle-controlled, phase II clinical trial was to determine the optimal regimen for the treatment, safety, and efficacy of VP-102 in external genital warts.

Methods: The study was conducted in two parts. Part A was dose finding and Part B was performed following the completion of Part A for a safety and efficacy evaluation. Following completion of Part A, 6-h and 24-h VP-102 regimens under occlusion were selected to be evaluated in Part B.

Results: Pooled results from Part B and Part A of the 6-h and 24-h VP-102 treatment regimens showed that 36.7% and 33.3% of participants achieved complete clearance of all treatable external genital warts at the end of treatment vs 4.2% (p < 0.0048) and 0% (p < 0.0075) with the vehicle. Adverse events experienced by the VP-102-treated participants were consistent with the pharmacodynamic action of cantharidin as a vesicant and were primarily mild to moderate in severity. The most common adverse events included application-site vesicles, pain, and erythema. No participants discontinued the study because of adverse events and no serious adverse events were deemed treatment related.

Conclusions: The adverse event profile and efficacy of VP-102 under occlusion demonstrated in this study support the conclusion that a 6-h or up to 24-h exposure regimen represents an acceptable risk:benefit profile and justifies the conduct of a larger vehicle-controlled phase III study in external genital warts.

Clinical trial registration: NCT03981822, actual study start date: 25 June, 2019; actual primary completion date: 21 May, 2020; actual study completion date: 8 July, 2020.

Conflict of interest statement

Drs. Guenthner, McFalda, and Tate received funding for clinical trials. Drs. Rieger and Glover are employees of PBM Capital Group. Dr. Andres, Ms. Willson, and Ms. Rumney are employees of Verrica Pharmaceuticals Inc. Dr. Olivadoti was an employee of Verrica Pharmaceuticals Inc. Dr. Rosen is a consultant for Verrica in activities unrelated to this trial.

© 2021. The Author(s).

Figures

Fig. 1

CARE-1 study design. AEs adverse events, EOT end of treatment

Fig. 2

Proportion of participants with complete clearance of external genital warts (EGW) at each visit (Pooled B and A, intent-to-treat [ITT] population). EOT end of treatment

Fig. 3

Mean percent change in external genital wart (EGW) count from baseline by study visit (Pooled B and A, intent-to-treat population). EOT end of treatment, MMRM mixed-effect model repeat measurement. P-value is based on MMRM with gender, treatment, visit, treatment by visit interaction, and baseline wart count as factors. An unstructured covariance model was used. Degrees of freedom associated with the error term were computed using the Kenward-Rogers method. Mean percent change reported are least-squares means