Topical Ruxolitinib Gel in Prurigo Nodularis: Phase I/II Trial
Key Takeaways
- This phase I/II, randomized, double-blind, vehicle-controlled, multicenter trial in China assigned 49 adults with prurigo nodularis 2:1 to HDM3010 or vehicle across once-daily and twice-daily cohorts.
- Treatment-emergent events were infrequent overall, treatment-related events occurred in 4.1% of participants and were mild to moderate, and steady-state mean peak plasma concentrations remained below 7 ng/mL.
- HDM3010 was associated with higher proportions of at least 4-point WI-NRS responders and greater improvement in WI-NRS, IGA PN-S, and IGA PN-A, but differences were not statistically significant and larger, longer trials were proposed.
Eligible participants were adults aged 18 to 65 years with prurigo nodularis for at least 3 months. Entry criteria included an IGA PN-S score of at least 2 and a weekly average WI-NRS score of at least 7 before randomization. Overall, 79.6% of participants had moderate-to-severe disease. Cohort assignments were HDM3010 n=16 and vehicle n=8 in the once-daily cohort, and HDM3010 n=16 and vehicle n=9 in the twice-daily cohort. Safety and tolerability were the primary outcomes, while pharmacokinetics and preliminary efficacy were secondary measures in this early-stage topical study.
During the double-blind period, treatment-emergent adverse events occurred in 18.8% of HDM3010 once-daily patients, 25.0% of HDM3010 twice-daily patients, 12.5% of vehicle once-daily patients, and 55.6% of vehicle twice-daily patients. Overall incidence was 26.5%, or 13 of 49 participants, and treatment-related adverse events occurred in 4.1%, all with mild-to-moderate severity. Most events were grade 1 or 2, no event occurred in two or more patients, no treatment-emergent adverse event or serious adverse event led to discontinuation or withdrawal, and no adverse events of special interest were reported. Investigators also noted one grade 3 hypertensive aggravation considered possibly unrelated, transient application-site pruritus and pain in one once-daily HDM3010 recipient, and liver enzyme elevations in one twice-daily recipient with pre-existing fatty liver disease and hepatitis B serology. Short-term tolerability was largely mild and did not interrupt treatment.
Pharmacokinetic analyses in 32 participants showed low systemic exposure after topical dosing, with mean peak plasma concentrations below 7 ng/mL at steady state. After the first dose, geometric mean Cmax was 0.513 ng/mL in the once-daily cohort and 1.14 ng/mL in the twice-daily cohort. Geometric mean AUC0–t values were 7.44 and 7.73 h·ng/mL, respectively, and the observed accumulation ratio after repeated dosing was about 3 to 4. The authors described the gel as a localized delivery approach intended to provide lesional exposure while reducing systemic exposure. These pharmacokinetic findings were consistent with that objective.
Across exploratory efficacy measures, HDM3010 was associated with higher proportions of at least 4-point WI-NRS responders and greater improvement in WI-NRS, IGA PN-S, and IGA PN-A than vehicle. No between-group comparison reached statistical significance during the blinded period. Week 8 observations were available only for participants who entered the extension phase, so they do not carry the same blinded comparison context. The authors interpreted the findings as showing a favorable short-term safety profile, minimal systemic exposure, and positive trends in reducing pruritus and lesions, while noting the small sample, limited treatment duration, lack of power for formal hypothesis testing, possible baseline severity imbalance favoring greater disease burden in the twice-daily cohort, and limited generalizability to milder prurigo nodularis. They concluded that the results support larger and longer randomized evaluation rather than definitive evidence of efficacy.