TY - JOUR
T1 - Design of Effisayil™ 2
T2 - A Randomized, Double-Blind, Placebo-Controlled Study of Spesolimab in Preventing Flares in Patients with Generalized Pustular Psoriasis
AU - Morita, Akimichi
AU - Choon, Siew Eng
AU - Bachelez, Hervé
AU - Anadkat, Milan J.
AU - Marrakchi, Slaheddine
AU - Zheng, Min
AU - Tsai, Tsen Fang
AU - Turki, Hamida
AU - Hua, Harry
AU - Rajeswari, Sushmita
AU - Thoma, Christian
AU - Burden, A. David
N1 - Funding Information:
The authors would like to thank the patients and their caregivers, in addition to the investigators and their teams, who will be involved in the Effisayil 2 study, which is supported and funded by Boehringer Ingelheim. The authors would like to acknowledge the meaningful contributions made by Ming Tang, an employee of Boehringer Ingelheim, in the development of the manuscript. The study was supported and funded by Boehringer Ingelheim. The journal’s Rapid Service Fee was funded by Boehringer Ingelheim. Derah Saward-Arav, PhD, of OPEN Health Communications (London, UK) provided writing, editorial and formatting support, which was contracted and funded by Boehringer Ingelheim. HH, SR, and CT contributed to the concept of the study. HH provided statistical expertise. All authors were involved in the study design; critically revised the manuscript content; provided their approval of the final manuscript version; and provided their agreement to be accountable for all aspects of the work. The design and rationale of the Effisayil™ 2 study was presented at the 30th European Academy of Dermatology and Venereology Congress (29 September–2 October 2021, Virtual), poster P1034.
Funding Information:
The authors would like to thank the patients and their caregivers, in addition to the investigators and their teams, who will be involved in the Effisayil 2 study, which is supported and funded by Boehringer Ingelheim. The authors would like to acknowledge the meaningful contributions made by Ming Tang, an employee of Boehringer Ingelheim, in the development of the manuscript.
Publisher Copyright:
© 2022, The Author(s).
PY - 2023/1
Y1 - 2023/1
N2 - Introduction: Generalized pustular psoriasis (GPP) is a rare autoinflammatory skin disease characterized by flares of widespread erythema with sterile pustules, and can be relapsing with recurrent flares, or persistent with intermittent flares. Spesolimab, a humanized anti-interleukin-36 (IL-36) receptor monoclonal antibody, targets the key IL-36 pathogenetic pathway in GPP. A previous study showed that spesolimab treatment led to rapid pustular and skin clearance in patients with GPP flares, which was sustained for up to 12 weeks. This study investigates the long-term effects of spesolimab on GPP flares, for which no specific treatments are currently available. The Effisayil™ 2 study will assess whether maintenance treatment with subcutaneous spesolimab prevents the occurrence of GPP flares and determine the optimal dosing regimen to achieve this aim. Methods: Patients will have a documented history of GPP with a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) score of 0 or 1 (clear or almost clear) at screening and randomization. Patients will be randomized 1:1:1:1 to three groups receiving a 600-mg subcutaneous loading dose of spesolimab followed by a 300-mg maintenance dose administered every 4 or 12 weeks, or a 300-mg loading dose followed by a 150-mg maintenance dose administered every 12 weeks, and one group receiving placebo, for 48 weeks. The primary endpoint is time to first GPP flare. If a patient experiences a GPP flare during the randomized maintenance treatment period, an open-label intravenous dose of 900-mg spesolimab will be administered, with an option for a second intravenous dose after 1 week. Conclusions: Effisayil™ 2 is the first placebo-controlled study in patients with GPP to investigate whether maintenance treatment with spesolimab can prevent flares and provide sustained disease control. This study will provide valuable insights on the long-term management of patients with this potentially life-threatening skin disease. Trial Registration Number: NCT04399837.
AB - Introduction: Generalized pustular psoriasis (GPP) is a rare autoinflammatory skin disease characterized by flares of widespread erythema with sterile pustules, and can be relapsing with recurrent flares, or persistent with intermittent flares. Spesolimab, a humanized anti-interleukin-36 (IL-36) receptor monoclonal antibody, targets the key IL-36 pathogenetic pathway in GPP. A previous study showed that spesolimab treatment led to rapid pustular and skin clearance in patients with GPP flares, which was sustained for up to 12 weeks. This study investigates the long-term effects of spesolimab on GPP flares, for which no specific treatments are currently available. The Effisayil™ 2 study will assess whether maintenance treatment with subcutaneous spesolimab prevents the occurrence of GPP flares and determine the optimal dosing regimen to achieve this aim. Methods: Patients will have a documented history of GPP with a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) score of 0 or 1 (clear or almost clear) at screening and randomization. Patients will be randomized 1:1:1:1 to three groups receiving a 600-mg subcutaneous loading dose of spesolimab followed by a 300-mg maintenance dose administered every 4 or 12 weeks, or a 300-mg loading dose followed by a 150-mg maintenance dose administered every 12 weeks, and one group receiving placebo, for 48 weeks. The primary endpoint is time to first GPP flare. If a patient experiences a GPP flare during the randomized maintenance treatment period, an open-label intravenous dose of 900-mg spesolimab will be administered, with an option for a second intravenous dose after 1 week. Conclusions: Effisayil™ 2 is the first placebo-controlled study in patients with GPP to investigate whether maintenance treatment with spesolimab can prevent flares and provide sustained disease control. This study will provide valuable insights on the long-term management of patients with this potentially life-threatening skin disease. Trial Registration Number: NCT04399837.
KW - Biologics
KW - Clinical trials
KW - Generalized pustular psoriasis
KW - Immunomodulatory therapies
KW - Inflammatory skin diseases
KW - Spesolimab
UR - http://www.scopus.com/inward/record.url?scp=85141426716&partnerID=8YFLogxK
U2 - 10.1007/s13555-022-00835-6
DO - 10.1007/s13555-022-00835-6
M3 - Article
C2 - 36333618
AN - SCOPUS:85141426716
SN - 2193-8210
VL - 13
SP - 347
EP - 359
JO - Dermatology and Therapy
JF - Dermatology and Therapy
IS - 1
ER -