Design of Effisayil™ 2: A Randomized, Double-Blind, Placebo-Controlled Study of Spesolimab in Preventing Flares in Patients with Generalized Pustular Psoriasis

Abstract

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.

Keywords: Biologics; Clinical trials; Generalized pustular psoriasis; Immunomodulatory therapies; Inflammatory skin diseases; Spesolimab.

© 2022. The Author(s).

Figures

Fig. 1

Overall study design, with loading and maintenance phase treatment arms, and handling of GPP flares during the randomized maintenance treatment period. *GPP flare defined as an increase in GPPGA total score of ≥ 2 from baseline and the pustular component of GPPGA of ≥ 2. †Administered 1 week after initial treatment with OL spesolimab in response to a GPP flare if patients meet qualifying criteria: for patients with GPPGA total score of ≥ 3 and a pustular component of GPPGA of ≥ 2 at baseline, if the GPPGA total score is ≥ 2 and the pustular component of GPPGA is ≥ 2; and for patients with GPPGA total score of 2 and a pustular component of GPPGA of ≥ 2 at baseline, if the pustular component of GPPGA is ≥ 2. ‡12 weeks after initial treatment with OL spesolimab in response to a GPP flare. §Other medication for GPP may be prescribed, but intensified spesolimab maintenance should be attempted first. ¶Patients may be treated with other medication for GPP at the investigator’s discretion, but the patient will be discontinued from any further study drug. GPP generalized pustular psoriasis, GPPGA Generalized Pustular Psoriasis Physician Global Assessment, IV intravenous, LD loading dose, OL open-label, OLE open-label extension, q4w every 4 weeks, q12w every 12 weeks, R randomization, SC subcutaneous