Study protocol of the global Effisayil 1 Phase II, multicentre, randomised, double-blind, placebo-controlled trial of spesolimab in patients with generalized pustular psoriasis presenting with an acute flare
Journal
BMJ Open
Journal Volume
11
Journal Issue
3
Date Issued
2021
Author(s)
Choon S.E.
Lebwohl M.G.
Marrakchi S.
Burden A.D.
Morita A.
Navarini A.A.
Zheng M.
Xu J.
Turki H.
Rajeswari S.
Deng H.
Tetzlaff K.
Thoma C.
Bachelez H.
Abstract
Introduction Generalized pustular psoriasis (GPP) is a rare, potentially life-threatening disease characterised by recurrent flares of widespread neutrophilic aseptic skin pustular eruption. Despite the availability of approved biologics for GPP in Japan, Taiwan and Thailand, associated evidence is largely based on uncontrolled studies in which acute flares were not directly assessed. Therefore, there is a high unmet need to investigate new rapid-acting effective treatments that resolve symptoms associated with acute GPP flares. A prior Phase I proof-of-concept study showed rapid improvements in skin and pustule clearance with a single intravenous dose of spesolimab, a novel anti-interleukin-36 receptor antibody, in patients presenting with an acute GPP flare. Here, we present the design and rationale of Effisayil 1, a global, Phase II, placebo-controlled study to evaluate the efficacy, safety and tolerability of spesolimab in patients presenting with an acute GPP flare. Methods and analysis At least 51 patients with an acute GPP flare will be randomised 2:1 to receive a single 900 mg intravenous dose of spesolimab or placebo and followed for up to 28 weeks. The primary endpoint is a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) pustulation subscore of 0 (pustule clearance) at Week 1. The key secondary endpoint is a GPPGA score of 0 or 1 (clear or almost clear) at Week 1. Safety will be assessed over the study duration by the occurrence of treatment-emergent adverse events. Blood and skin biopsies will be collected to assess biomarkers. Superiority of spesolimab over placebo in the proportion of patients achieving the primary and key secondary endpoints will be evaluated. Ethics and dissemination The study complies with the ethical principles of the Declaration of Helsinki, the International Council for Harmonisation's Good Clinical Practice and local regulations. Ethics committee approvals have been obtained for each centre from all participating countries and are listed in online supplementary file 1. Primary results will be published in a peer-reviewed journal. Trial registration details ClinicalTrials.gov identifier: NCT03782792; Pre-results. ? Author(s) 2021.
Subjects
clinical trials; dermatopathology; psoriasis
SDGs
Other Subjects
biological marker; placebo; spesolimab; adult; aged; Article; blood analysis; clinical assessment; clinical protocol; controlled study; disease exacerbation; double blind procedure; drug efficacy; drug safety; drug tolerability; female; follow up; human; human cell; human tissue; major clinical study; male; multicenter study; phase 2 clinical trial; pustular psoriasis; randomized controlled trial; scoring system; single drug dose; skin biopsy; symptom assessment; treatment response; Japan; multicenter study (topic); phase 2 clinical trial (topic); psoriasis; randomized controlled trial (topic); Taiwan; Thailand; treatment outcome; Clinical Trials, Phase II as Topic; Double-Blind Method; Humans; Japan; Multicenter Studies as Topic; Psoriasis; Randomized Controlled Trials as Topic; Taiwan; Thailand; Treatment Outcome
Publisher
BMJ Publishing Group
Type
journal article