Phase 2 Trial of a Neurokinin-1 Receptor Antagonist for the Treatment of Chronic Itch in Epidermolysis Bullosa Patients: A Randomized Clinical Trial

Abstract BACKGROUND Chronic pruritus causes major morbidity in epidermolysis bullosa (EB). The substance P-neurokinin 1 receptor (SP-NK1) pathway is a promising target for treating EB-related pruritus. OBJECTIVE To evaluate the safety and efficacy of oral NK1 receptor antagonist serlopitant in treating moderate-severe pruritus in EB. METHODS 14 patients were randomized to serlopitant or placebo for 8 weeks, followed by a 4-week washout and optional open-label extension. The primary endpoint was change in itch as measured by a numeric rating scale (NRS). Secondary endpoints were change in: (1) itch during dressing changes and (2) wound size. RESULTS We observed greater itch reduction with serlopitant, equivalent to a 0.64-point comparative reduction on the 11-point NRS by week 8, though this failed to meet statistical significance (p=0.11). More serlopitant patients achieved ≥3-point reduction compared to placebo (43% vs. 14%, p=0.35). In post hoc analysis excluding one subject with a concurrent seborrheic dermatitis flare, serlopitant achieved significantly greater median itch reduction from baseline by week 4 (-2 points vs. 0, p=0.01). We observed no statistically significant differences in secondary endpoints. Serlopitant was well-tolerated. LIMITATIONS Small sample size due to disease rarity CONCLUSION The potential itch reduction with serlopitant observed in this trial will be pursued by a larger powered trial (NCT03836001).