26590 Design and Rationale of Effisayil 1, a Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Spesolimab in Patients with Generalized Pustular Psoriasis with an Acute Flare

Generalized pustular psoriasis (GPP) is a rare, potentially life-threatening disease characterized by recurrent flares of widespread skin eruptions of neutrophilic aseptic pustules that occur with or without systemic inflammation. Therapeutic intervention is a major challenge; globally, there are no approved treatments for acute GPP flares and there is a lack of robust clinical evidence to guide GPP treatment. Rapid improvements in skin symptoms with a single intravenous dose of spesolimab, an anti-IL-36 receptor antibody, was shown in a prior Phase I study. Here, we present the design and rationale of Effisayil 1, a global, Phase II, placebo-controlled trial to evaluate the efficacy and safety of spesolimab in patients presenting with an acute GPP flare (NCT03782792). At least 51 patients presenting with an acute GPP flare will be randomized 2:1 to receive a single 900-mg intravenous dose of spesolimab or placebo, followed for up to 28 weeks. The primary endpoint is the achievement of a GPP Physician Global Assessment (GPPGA) pustulation subscore of 0 (pustule clearance) at Week 1. The key secondary endpoint is a GPPGA score of 0/1 (clear/almost clear) at Week 1. Any patient who experiences disease worsening and/or flare reoccurrence will be offered escape and/or rescue treatment with standard of care or open-label spesolimab, respectively. Treatment-emergent adverse events will be assessed over the study duration. Biomarker analyses will be conducted in blood and lesional skin biopsies. This is the first randomized, placebo-controlled trial in acute GPP flares, and will provide robust evidence on early intervention with spesolimab.