A randomised, parallel-group, double-blind, placebo-controlled phase 3 study to Determine the effectiveness of the type I interferon receptor antibody, Anifrolumab, In SYstemic sclerosis: DAISY study design and rationale.

Objectives: The type I interferon pathway is a promising target for treatment of patients with systemic sclerosis (SSc). Here, we describe the design of a multinational, randomised phase 3 study to Determine the effectiveness of the type I interferon receptor antibody, Anifrolumab, In SYstemic sclerosis (DAISY).

Methods: DAISY includes a 52-week double-blind, placebo-controlled treatment period, a 52-week open-label active treatment period, and a 12-week safety follow-up period. The patient population includes a planned 306 adults with limited or diffuse cutaneous active SSc who satisfied American College of Rheumatology/European Alliance of Associations for Rheumatology 2013 SSc criteria. Use of standard immunosuppressants, including mycophenolate mofetil, at a stable dose prior to randomisation is permitted in addition to weekly subcutaneous anifrolumab or placebo. Efficacy will be assessed at Week 52 via Revised-Composite Response Index in SSc (CRISS)-25 response (primary endpoint). Lung function and skin thickness will be assessed via change from baseline in forced vital capacity in patients with SSc-associated interstitial lung disease and modified Rodnan Skin Score, respectively (key secondary endpoints).

Conclusions: The DAISY trial will evaluate the efficacy and safety of anifrolumab as a first-in-class treatment option for patients with both limited and diffuse cutaneous SSc and will provide insight into the contributions of type I interferon to SSc pathogenesis. Revised-CRISS-25 can account for improvement and worsening in a broad set of validated clinical measures beyond lung function and skin thickness, including clinician- and patient-reported outcomes, capturing the heterogeneity of SSc.