Efficacy and safety of a topical nitric oxide–releasing solution (NORS) as a noninvasive treatment for plantar warts (verrucae plantaris)

BACKGROUND: Plantar warts (verrucae plantaris), caused by human papillomavirus, are common and often resistant to standard therapies, which can be painful and damaging. Novel, noninvasive options are needed. OBJECTIVE: To evaluate the safety and preliminary efficacy of a topical nitric oxide-releasing solution (NORS) as a self-administered therapy for plantar warts. METHODS: In this Phase 2a, multicenter, randomized, double-blind, placebo-controlled trial, 20 participants with ≥3 plantar warts were randomized (1:1:1) to NORS 1X (41.1 PPM·min), NORS 3X (121.9 PPM·min), or placebo. Participants completed 15-minute footbaths three times weekly for 3 weeks, followed by 2 weeks of observation. The primary endpoint was complete wart clearance at Day 35; secondary endpoints included ≥70% wart area reduction, pain change, and Physician Wart Assessment (PWA) grading. RESULTS: ≥ 70% wart area reduction occurred in 21%, 16%, and 12%, respectively. Pain improvement and a 50% reduction in severe warts (PWA grade 3) were observed only with NORS 3X. CONCLUSION: NORS demonstrated favorable safety and early clinical activity, warranting larger, longer-term efficacy trials. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT05877313.