Jeffrey Cheah School of Medicine and Health Sciences, Clinical School Johor Bahru, Monash University Malaysia, Johor Bahru, Johor, Malaysia.
Icahn School of Medicine at Mount Sinai, New York, New York, USA.
BMJ Open. 2021 Mar 30;11(3):e043666. doi: 10.1136/bmjopen-2020-043666.
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.
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.
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.
ClinicalTrials.gov identifier: NCT03782792; Pre-results.
泛发性脓疱型银屑病（GPP）是一种罕见的、潜在危及生命的疾病，其特征是广泛的中性粒细胞无菌性皮肤脓疱性发作反复发作。尽管在日本、中国台湾地区和泰国已经有针对 GPP 的生物制剂获批，但相关证据主要基于未进行直接评估急性发作的对照研究。因此，有很高的未满足需求来研究新的起效迅速且有效的治疗方法，以解决与 GPP 急性发作相关的症状。一项 I 期概念验证研究表明，在出现 GPP 急性发作的患者中，单次静脉注射新型白细胞介素-36 受体抗体 spesolimab 可快速改善皮肤和脓疱清除，达到临床意义。在此，我们介绍了一项全球、II 期、安慰剂对照研究的设计和原理，该研究旨在评估 spesolimab 治疗 GPP 急性发作患者的疗效、安全性和耐受性。
至少 51 例 GPP 急性发作患者将以 2:1 的比例随机接受单次 900mg 静脉注射 spesolimab 或安慰剂，并随访 28 周。主要终点是第 1 周时广义脓疱型银屑病医生总体评估（GPPGA）脓疱亚评分 0（脓疱清除）。关键次要终点是第 1 周时 GPPGA 评分为 0 或 1（清除或几乎清除）。研究期间将通过治疗后出现的不良事件评估安全性。将采集血液和皮肤活检样本以评估生物标志物。将评估 spesolimab 相对于安慰剂在达到主要和关键次要终点的患者比例方面的优越性。
该研究符合《赫尔辛基宣言》的伦理原则、国际协调理事会良好临床实践和当地法规。每个参与国家的所有中心都已获得伦理委员会的批准，并在在线补充文件 1 中列出。主要结果将发表在同行评议的期刊上。
ClinicalTrials.gov 标识符：NCT03782792；预结果。
