Cantharidin Application in Patients With Common Warts (Verruca Vulgaris) (COVE-3)

Methodology:

This Phase 3, double-blind, randomized, vehicle-controlled study (Study number VP-CW-302; referred to as COVE-3 [Cantharidin and Occlusion in Verruca Epithelium 3]) includes a Screening Period of up to 60 days, followed by a 75-day Treatment Period, and a 63-day Follow-up Period.

Treatments:

Treatment Visit 1 (Day 1), the day of the first application of study drug (YCANTH [VP-102/TO-208] or Vehicle), may occur on the same day as the Screening Visit. Dermatologic examination, wart measurements, location of all treatable common warts, and evaluation of response to treatment (ERT; as defined in Assessments and procedures) must be repeated if the Screening Visit and Treatment Visit 1 do not coincide. YCANTH (VP-102/TO-208) or Vehicle will be applied by the Investigator or qualified member of the research team. Study drug will be applied to treatable common warts, including an approximate 1 to 2 mm margin of healthy, surrounding skin. Warts are to be treated, then covered with occlusive tape (occlusive tape with similar properties should be used across all clinical sites) that will remain in place overnight and be removed just before the 24 hour evaluation of response to treatment (ERT).

Before application of study drug, wart paring, if necessary, will be completed. If adherent scale is not present, study drug can be applied without paring.

Treatment will continue every 21 (±4) days until complete clearance of all warts or a maximum of 4 treatment sessions during the 75-day treatment period. The exact treatment interval will be determined by evaluation of the treatment site, taking into account ongoing local skin reactions (LSRs), which are defined as temporary local skin reactions (vesiculation, pain, pruritus, scabbing, erythema, discoloration, application site dryness, edema and erosion. that are expected and consistent with historical treatment with YCANTH (VP-102/TO-208). Subjects will be required to return for every treatment and follow-up visit even if their treatable common warts have cleared. Subjects will have an in person visit 24 (± 6) hours after Treatment Visit 1 (first application of study drug). After Treatment Visits 2, 3, and 4 (Days 21, 42, and 63, respectively), telephone follow-up will be conducted 24 to 72 hours after application of study drug. In addition, telephone follow-up will be conducted 7 to10 days after application of study drug after Treatment Visits 1,2,3 and 4. During the telephone calls, a member of the research team will complete ERT assessments and inquire about AEs and concomitant medications.

Assessment for complete clearance (i.e., complete resolution of all common warts as assessed visually by a Blinded Assessor) may be made once all treatable common warts are evaluable and not obscured by an ongoing LSR. If the Investigator is unable to evaluate or treat 1 or more warts due to ongoing LSRs, no warts should be treated; the visit will be documented as an Unscheduled Visit. The timing of the next visit will be determined by resolution of the LSRs. All LSRs must resolve sufficiently to allow for evaluation of the treatment site. The research team will be in contact with the subject until all LSRs are resolved. Once LSRs have resolved, a Treatment Visit will be scheduled within 21 (± 4) days of the previous treatment application, noting it may be longer than 21 (± 4) days depending on the length of time until LSR resolution. A treatment interval exceeding 21 (± 4) days because of resolving LSRs will not be considered a protocol deviation.

All treatable common warts that are not completely clear should undergo treatment with study drug. No partial treatment of treatable common warts is permitted, unless a subject would be required to exceed the maximum number of 2 applicators per treatment session in order to complete treatment. Each applicator can cover approximately 1500 mm2 for a total of approximately 3000 mm2 using the 2 study drug applicators.

If a subject receives fewer than 4 treatments within the 75-day treatment period because of the duration of post-treatment LSRs, this will not be considered a protocol deviation. No treatment should be administered after the 75-day treatment period without Sponsor approval.

Subjects will be required to attend all visits even if they have achieved complete clearance of all treatable common warts at a previous visit.

Subjects enrolled in Japan in this study (COVE-3) will be eligible to enroll in a Long-Term Follow-up (LTFU) study (Study VP-CW-303 [COVE-4]) to evaluate the safety and efficacy of YCANTH (VP-102/TO-208) over 54 weeks:

• Subjects who have completed the in-person Day 84 (0 to + 8 days; End-of-Treatment/End-of-Study 1) Visit and have complete clearance will be assessed at follow-up visits on Day 105 (± 7 days; Follow-up 1/End-of-Study 2) and Day 147 (± 7 days; Follow-up 2/End-of-Study 3).
• Japanese subjects who have not achieved complete clearance of all treatable common warts by Day 84, and those who have new treatable common warts or recurrence of previously treated warts after Day 84 (ie, at Day 105 or Day 147) will be eligible to transition into the LTFU study.
• At Day 147, all Japanese subjects remaining in COVE-3 will be eligible to transition into the LTFU study for continued follow-up and treatment.

In the LTFU study, eligible Japanese subjects will receive open-label YCANTH (VP-102/TO-208) every 21 days until all treatable common warts are clear (for a maximum of 4 additional treatments) or until Day 357, whichever occurs first.