Trial of Efficacy and Safety of NS-229 Versus Placebo in Patients With Eosinophilic Granulomatosis With Polyangiitis

The purpose of this randomized, double-blind study is to investigate the efficacy and safety of NS229 compared with placebo over a 28-week study treatment period in subjects with Eosinophilic Granulomatosis with Polyangiitis (EGPA) receiving background corticosteroid therapy with or without Mepolizumab/Benralizumab therapy. During the treatment period corticosteroid dose will be tapered.

The key outcomes in the study focus on evaluation of clinical remission, defined as Birmingham Vasculitis Activity Score (BVAS)=0 with a corticosteroid dose of <=4 mg/day prednisolone/prednisone.

Inclusion criteria

• Ability to provide written informed consent prior to participation in the study.
• Male or female subjects aged ≥18 years at the time the informed consent form is signed.
• Diagnosis of EGPA: Subjects who have been diagnosed with EGPA based on the history or presence of eosinophilia plus at least a history or presence of 2 of additional features of EGPA.
• Subjects receive background OGC dose of ≥7.5 mg/day with or without stable treatment with Mepolizumab/Benralizumab.
• Use of adequate contraception.
• Other inclusion criteria may apply.

Exclusion criteria

• Current diagnosis of either granulomatosis with polyangiitis or microscopic polyangiitis
• Imminently life-threatening EGPA at the time of screening.
• History or presence of any form of cancer within 5 years prior to screening.
• Serious liver, renal, blood, or psychiatric disease
• Severe or clinically significant cardiovascular disease uncontrolled with standard treatment
• Active systemic infections (including TB, pneumonia, Pneumocystis pneumonia, sepsis, and opportunistic infections)
• Parasitic infection: Subjects with a known parasitic infestation within 6 months prior to screening.
• HIV positive status
• Active hepatitis due to hepatitis B virus or hepatitis C virus
• Known history or presence of venous thromboembolism/venous thrombotic events (deep vein thrombosis and/or pulmonary embolus)
• laboratory parameter exclusions:

• Estimated glomerular filtration rate of <30 mL/min/1.73 m2 by Chronic Kidney Disease Epidemiology Collaboration equations
• WBC count <4 × 109/L
• Absolute lymphocyte count <500 cells/mm3
• Absolute neutrophil count <1000 cells/mm3
• Platelet count <120,000/mm3
• Hemoglobin <8 g/dL (<80 g/L)
• Subjects who are pregnant, breastfeeding, or planning to become pregnant during the time of study participation
• History of clinically significant drug or alcohol abuse within the last 6 months
• Other exclusion criteria may apply.