Trial of efficacy and safety of NS-229 versus placebo in patients with Eosinophilic Granulomatosis With Polyangiitis

Phase 1

Recruiting

Conditions: Eosinophilic granulomatosis with polyangiitis (EGPA)
MedDRA version: 20.0Level: PTClassification code: 10078117Term: Eosinophilic granulomatosis with polyangiitis Class: 100000004870
Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Registration Number: CTIS2023-504245-32-00

Lead Sponsor: s Pharma Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: All

Target Recruitment: 45

Inclusion Criteria

1) Ability to provide written informed consent prior to participation in the study. Subjects must be able to read, comprehend, and write at a level sufficient to complete study-related materials, 2) Male or female subjects aged =18 years at the time the informed consent form is signed, 3) 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 the following additional features of EGPA: a) A biopsy showing histopathological evidence of eosinophilic vasculitis, perivascular eosinophilic infiltration, or eosinophil-rich granulomatous inflammation b) Neuropathy, mono or poly c) Pulmonary infiltrates, non-fixed d) Sinonasal abnormality e) Cardiomyopathy f) Glomerulonephritis g) Alveolar hemorrhage h) Palpable purpura i) Positive test result for ANCA j) Asthma, 4) A BVAS of =3 within 28 days prior to screening and a prednisolone/prednisone dose at screening of =7.5 mg/day; OR A BVAS of =3 within 60 days prior to screening and a prednisolone/prednisone dose at screening of =20 mg/day, 5) Female subjects of childbearing potential must commit to the consistent and correct use of a highly effective method of contraception from the time of informed consent until 90 days after the last dose of study treatment

Exclusion Criteria

1) Current diagnosis of either granulomatosis with polyangiitis or microscopic polyangiitis, 18) Subjects who are pregnant, breastfeeding, or planning to become pregnant during the time of study participation, 19) History of clinically significant drug or alcohol abuse within the last 6 months, 2) Imminently life-threatening EGPA defined as the presence of any of the following manifestations as active disease at the time of screening: a) Hospitalization in an intensive care unit b) Severe alveolar hemorrhage requiring transfusion or ventilation, or hemoglobin <8 g/dL (<80 g/L) or drop in hemoglobin of >2 g/dL (>20 g/L) over a 48-hour period due to alveolar hemorrhage c) Rapidly progressive glomerulonephritis over a 48-hour period d) Severe gastrointestinal involvement e) Severe central nervous system involvement f) Severe cardiac involvement, 20) Receipt of treatment with an IP within the past 30 days or 5 terminal phase half-lives of the IP, whichever is longer, prior to screening, 21) Current participation in any other interventional clinical study, 22) Unwilling or unable to comply with the protocol, 23) Suspected, probable, or confirmed diagnosis of active COVID-19, 24) Other concurrent disease and/or medical condition that may put the subject at risk or may influence the results of the study or the subject’s ability to complete the entire duration of the study, 3) History or presence of any form of cancer within 5 years prior to screening, with the exception of excised basal cell or squamous cell carcinoma of the skin, or carcinoma in situ such as cervical or breast carcinoma in situ that has been excised or resected completely and is without evidence of local recurrence or metastasis., 4) Serious liver, renal, blood, or psychiatric disease a) Moderate and severe hepatic impairment by the Child-Pugh scoring system, 10) Parasitic infection: Subjects with a known parasitic infestation within 6 months prior to screening, 5) Severe or clinically significant cardiovascular disease uncontrolled with standard treatment, 6) Electrocardiogram measurement of corrected QT by Fridericia >450 ms, 7) Other concurrent medical conditions: Subjects who have known, preexisting, clinically significant endocrine, autoimmune, metabolic, neurologic, renal, gastrointestinal, hepatic, hematologic, respiratory, or any other system abnormalities that are not associated with EGPA and are uncontrolled with standard treatment and considered by the Investigator to be a contraindication for the subject to participate in the study, 8) Active tuberculosis (TB) or meets TB exclusionary parameters, 9) Active systemic infections, 25) French subjects: persons under court protection, persons not affiliated to a social security system, protected adults ((Art. L. 1121-5), Art. L. 1121-6, Art. L. 1121-8, Art. L. 1121-8-1)., 11) HIV-positive status, 12) Active hepatitis due to hepatitis B virus or hepatitis C virus, 13) History of hypersensitivity to the investigational product (IP) and prednisolone/prednisone, its excipients, or similar drugs (JAK inhibitors) and if used, to mepolizumab., 14) Known history or presence of venous thromboembolism/venous thrombotic events, 15) Use of any of the following prohibited medications within the time points specified: a) Requirement of an OGC dose of prednisolone/prednisone >60 mg/day at baseline b) Previous receipt of a Janus kinase inhibitor c) Initiation of treatment with mepolizumab after screening d) Omalizumab within 130 days

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objectives of the study are to investigate the efficacy and safety of NS 229 compared with placebo by analyzing number of EGPA subjects in remission, and number of adverse events.;Secondary Objective: The secondary objectives of the study are to investigate the efficacy and safety of NS 229 compared with placebo by analyzing number of EGPA subjects in remission and time to worsening/relapse of EGPA.;Primary end point(s): Primary Efficacy Endpoint: The proportion of subjects in remission (oral glucocorticoid [OGC] 4.0) at Week 28 of the study treatment period., Primary Safety Endpoints: Number of adverse events (AEs) including AEs that may be treatment-related and severe reactions, some of which may be treatment-related.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s):Secondary Efficacy Endpoints: The proportion of subjects in remission (OGC 7.5) at Week 28 of the study treatment period;Secondary end point(s):Secondary Efficacy Endpoints: Time to first relapse of EGPA (active disease since the last visit after achieved decrease);Secondary end point(s):Secondary Efficacy Endpoints: Time to first worsening of EGPA (worsening of active disease since the last visit)