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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

Choon SE 1 , Lebwohl MG 2 , Marrakchi S 3 , Burden AD 4 , Tsai TF 5 , Morita A 6 Show all authors , Navarini AA 7 , Zheng M 8 , Xu J 9 , Turki H 3 , Rajeswari S 10 , Deng H 11 , Tetzlaff K 12 , Thoma C 13 , Bachelez H 14

Affiliations 

  • 1 Jeffrey Cheah School of Medicine and Health Sciences, Clinical School Johor Bahru, Monash University Malaysia, Johor Bahru, Johor, Malaysia
  • 2 Icahn School of Medicine at Mount Sinai, New York, New York, USA
  • 3 Dermatology Department, Hedi Chaker University Hospital, Sfax, Tunisia
  • 4 Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK
  • 5 Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
  • 6 Department of Geriatric and Environmental Dermatology, Nagoya City University, Graduate School of Medical Sciences, Nagoya, Japan
  • 7 Department of Dermatology, University Hospital Basel, Basel, Switzerland
  • 8 Department of Dermatology, Second Affiliated Hospital, Zhejiang University, School of Medicine, Hangzhou, China
  • 9 Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China
  • 10 Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut, USA
  • 11 Boehringer Ingelheim (China), Investment Co Ltd, Shanghai, China
  • 12 Boehringer Ingelheim International GmbH, Ingelheim, Germany
  • 13 Boehringer Ingelheim International GmbH, Biberach, Germany
  • 14 Service de Dermatologie, Assistance Publique-Hôpitaux de Paris Hôpital Saint-Louis, Paris, France herve.bachelez@aphp.fr
BMJ Open, 2021 03 30;11(3):e043666.
PMID: 33785490 DOI: 10.1136/bmjopen-2020-043666

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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