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

Study Overview
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Brief Summary
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This study will enroll male and female subjects who are 18 years of age or older with Eosinophilic Granulomatosis With Polyangiitis.

Detailed Description
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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 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.

Official Title
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A Phase 2, Double-blind, Randomized, Placebo-controlled Study to Investigate the Efficacy and Safety of NS-229 in the Treatment of Eosinophilic Granulomatosis With Polyangiitis

Conditions
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Eosinophilic Granulomatosis With Polyangiitis, Churg-Strauss Syndrome

Intervention / Treatment
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* Drug: NS-229
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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. 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 <500 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NS-229<br>Self-administer NS-229 in consecutive 28 weeks. | Drug: NS-229<br>* Experimental<br>|
| Placebo Comparator: Placebo<br>Self-administer matching placebo in consecutive 28 weeks. | Drug: Placebo<br>* Placebo comparator<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of subjects in remission [OGC 4.0] | The proportion of subjects in remission (oral glucocorticoid [OGC] 4.0) at Week 28 of the study treatment period. Definition of remission (OGC 4.0): BVAS of 0 AND OGC dose of prednisolone/prednisone ≤4 mg/day | From Baseline to week 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of subjects in remission [OGC 7.5] | The proportion of subjects in remission (OGC 7.5) at Week 28 of the study treatment period Definition of remission (OGC 7.5): BVAS of 0 AND OGC dose of prednisolone/prednisone ≤7.5 mg/day | From Baseline to week 28 | 
| Time to first relapse of EGPA | Relapse of EGPA will be defined as active disease since the last visit after remission (OGC 4.0) was achieved, characterized by: Active vasculitis (BVAS of >0); OR Signs and/or symptoms of active asthma with a corresponding worsening in answers on the 6-item Asthma Control Questionnaire (compared with the most recent previous results); OR Active nasal and/or sinus disease (attributable to EGPA) with a corresponding worsening in at least 1 of the answers on the sinonasal symptom questionnaire (compared with the most recent previous assessment). | Up to Week 28 | 
| Time to first worsening of EGPA | Worsening of EGPA will be defined as worsening of active disease since the last visit, characterized by: Active vasculitis (BVAS >0) and the score greater than the previous visit; OR Signs and/or symptoms of active asthma with a corresponding worsening in answers on the 6-item Asthma Control Questionnaire (compared to the most recent previous score); OR Active nasal and/or sinus disease (attributable to EGPA) with a corresponding worsening in at least 1 of the answers on the sinonasal symptom questionnaire (compared to the most recent previous assessment). | Up to Week 28 |