A three period multicenter study, with a randomized-withdrawal, double-blinded, placebo-controlled design in Period 2 to evaluate the clinical efficacy, safety and tolerability of MAS825 in NLRC4-GOF patients
What is the goal of the study?
Mutations in the NLRC4 gene result in multisystem autoinflammatory diseases characterized by elevation of pro-inflammatory inflammasome effector cytokines IL-1 β and IL-18. There are multiple NLRC4 inflammasomopathies, germ line de novo and inherited mutations result in NLRC4 gain of function (NLRC4-GOF). NLRC4-GOF presents clinically as very early onset infantile enterocolitis with sever diarrhea, ephemeral maculopapular and urticarial rashes, fever, cytopenias, and liver dysfunction and coagulopathy. Outcomes for NLRC4-GOF are poor, with most cases being fatal within weeks of diagnosis. Early treatment of MAS like features and enterocolitis is crucial to prevent irreversible organ damage and associated morbidity. Cyclosporin, anti-TNFα, systemic glucocorticoids and anti- IL-1β therapies alone or in combination have not improved outcomes for this disease. Currently, there are no approved therapeutics that directly and specifically target the underlying IL-1β and IL-18 driven autoinflammatory process. Only combined IL-1 β and IL-18 blockades have been successful in treating NLCR4-GOF, with one reported case of clinical improvement under this therapy in the literature. MAS825 is a heterodimeric Fc, monovalent format bispecific IgG1 monoclonal antibody composed of Novartis clinical stage anti-IL-1β (canakinumab) and IL-18 (CMK389) monoclonal antibodies in a single molecule. By simultaneously targeting and neutralizing both inflammasome effector cytokines IL- 1β and IL-18, MAS825 has potential as a therapeutic option for NLRC4-GOF. This study is a phase 2 trial designed to evaluate the clinical efficacy, safety and tolerability of MAS825 in patients with NLRC4-GOF.
Who can participate in the study?
Please contact the study team listed below to learn more.