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

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.