Safety, Pharmacokinetics, and Efficacy of 1.5% Ruxolitinib Gel (HDM3010) in Adult Patients with Prurigo Nodularis: A Phase I/II, Randomized, Double-Blind, Vehicle-Controlled Multicenter Clinical Trial

INTRODUCTION: Prurigo nodularis (PN) is a chronic inflammatory dermatosis with severe, persistent pruritus and limited effective therapies. Janus kinase (JAK) inhibition has emerged as a targeted strategy for PN. METHODS: This phase I/II, randomized, double-blind, vehicle-controlled, multicenter clinical trial was conducted in China to evaluate the safety, pharmacokinetics, and efficacy of topical 1.5% ruxolitinib gel (HDM3010) in adults with PN. Adult patients with PN were randomized 2:1 to receive HDM3010 or vehicle, administered once daily (QD) or twice daily (BID), during a 4-week double-blind treatment period. RESULTS: Forty-nine patients were randomized. HDM3010 demonstrated a safety profile characterized by treatment-emergent adverse events in 18.8% of QD and 25.0% of BID patients, compared with 12.5% of vehicle QD and 55.6% of vehicle BID patients. Treatment-related adverse events were infrequent (4.1%) and limited to mild-to-moderate severity. Pharmacokinetic analyses showed low systemic exposure, with mean peak plasma concentrations below 7 ng/mL at steady state. Compared with vehicle, HDM3010 was associated with higher proportions of ≥ 4-point Worst Itch Numerical Rating Scale (WI-NRS) responders and greater improvements in WI-NRS, Investigator's Global Assessment for Prurigo Nodularis-Stage (IGA PN-S), and Investigator's Global Assessment for Prurigo Nodularis-Activity (IGA PN-A) scores. CONCLUSIONS: HDM3010 demonstrated a favorable safety profile, minimal systemic exposure, and positive trends in reducing pruritus and lesions in adults with PN. TRIAL REGISTRATION: Chinese Clinical Trial Registry ( http://www.chictr.org.cn ): ChiCTR2500096434 (registered January 23, 2025).