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

Phase 2

Recruiting

Conditions: Eosinophilic granulomatosis with polyangiitis (EGPA)

Registration Number: 2023-504245-32-00

Lead Sponsor: Ns Pharma Inc.

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: Authorised, recruiting

Sex: Not specified

Target Recruitment: 20

Inclusion Criteria

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
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 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
4a: BVAS ≥3 on date of screening visit, using the standard 28-day look-back period and prednisone/prednisolone dose ≥7.5 mg/day. OR 4b: Disease activity of EGPA within 60 days of screening visit that is equivalent to BVAS ≥3 and prednisone/prednisolone dose ≥20 mg/day on day of screening.
Female subjects of childbearing potential must commit to the consistent and correct use of highly effective methods of contraception from the time of informed consent until 90 days after the last dose of study treatment. Male subjects with pregnant partners or nonpregnant partners of childbearing potential must agree to use adequate and reliable contraception from informed consent (screening) until 90 days after the last dose of study treatment. (see Appendix 3 for additional guidance).

Exclusion Criteria

Current diagnosis of either granulomatosis with polyangiitis or microscopic polyangiitis
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
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
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
Current participation in any other interventional clinical study
Unwilling or unable to comply with the protocol
Suspected, probable, or confirmed diagnosis of active COVID-19
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
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.
Serious liver, renal, blood, or psychiatric disease a) Moderate and severe hepatic impairment by the Child-Pugh scoring system
Parasitic infection: Subjects with a known parasitic infestation within 6 months prior to screening
Severe or clinically significant cardiovascular disease uncontrolled with standard treatment
Electrocardiogram measurement of corrected QT by Fridericia >450 ms
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
Active tuberculosis (TB) or meets TB exclusionary parameters [German, Italy, Spain, and French subjects:] Active, previous, or latent tuberculosis (TB) or meets TB exclusionary parameters
Active systemic infections
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).
HIV-positive status
Active hepatitis due to hepatitis B virus or hepatitis C virus
History of hypersensitivity to the investigational product (IP) and prednisolone/prednisone, its excipients, or similar drugs (JAK inhibitors) and if used, to mepolizumab or benralizumab.
Known history or presence of venous thromboembolism/venous thrombotic events
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 prior to baseline e) Rituximab within 180 days prior to baseline f) Dupilumab within 100 days prior to baseline g) Reslizumab within 120 days prior to baseline h) Initiation of treatment with Benralizumab after screening (Visit 1) i) Intravenous or subcutaneous immunoglobulin within 180 days prior to baseline j) Interferon-α within 180 days prior to baseline k) Antitumor necrosis factor therapy within 12 weeks prior to baseline l) Anti-CD52 within 180 days prior to baseline m) Cyclophosphamide (CYC): Subjects who received a CYC-based induction regimen may be randomized a minimum of 2 weeks after the last dose of daily oral CYC, or 3 weeks after the last dose of intravenous CYC, if their total WBC count is ≥4 × 109/L n) Any non-glucocorticoid immunosuppressive therapy (excluding CYC, mepolizumab or benralizumab) within 7 days prior to baseline o) The medications, as per the list of medications listed in Appendix 8 of the protocol, are prohibited within 7 days or 5 half-lives prior to baseline, whichever is longer.
Receipt of any live vaccine within 4 weeks prior to the first dose of study treatment or expected need for live vaccination during study participation including at least 4 weeks after the last dose of study treatment
Other laboratory parameter exclusions: a) Estimated glomerular filtration rate of <30 mL/min/1.73 m2 by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations (2021 CKD-EPI Creatinine) b) WBC count <4 × 109/L c) Absolute lymphocyte count <500 cells/mm3 d) Absolute neutrophil count <1000 cells/mm3 e) Platelet count <120,000/mm3 f) Hemoglobin <8 g/dL (<80 g/L)

Study & Design

Study Type: INTERVENTIONAL

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Primary Efficacy Endpoint: The proportion of subjects in remission (oral glucocorticoid [OGC] 4.0) at Week 28 of the study treatment period.		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.		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 Efficacy Endpoints: The proportion of subjects in remission (OGC 7.5) at Week 28 of the study treatment period		Secondary Efficacy Endpoints: The proportion of subjects in remission (OGC 7.5) at Week 28 of the study treatment period
Secondary Efficacy Endpoints: Time to first relapse of EGPA (active disease since the last visit after achieved decrease)		Secondary Efficacy Endpoints: Time to first relapse of EGPA (active disease since the last visit after achieved decrease)
Secondary Efficacy Endpoints: Time to first worsening of EGPA (worsening of active disease since the last visit)		Secondary Efficacy Endpoints: Time to first worsening of EGPA (worsening of active disease since the last visit)

Trial Locations

Locations (11): Hospital Universitario De Navarra
🇪🇸
Pamplona, Spain
Complexo Hospitalario Universitario De Santiago
🇪🇸
Santiago De Compostela, Spain
Centre Hospitalier Universitaire De Nice
🇫🇷
Nice, France
Assistance Publique Hopitaux De Paris
🇫🇷
Paris, France
Centre Hospitalier Universitaire De Toulouse
🇫🇷
Toulouse Cedex 9, France
Azienda Provinciale Per I Servizi Sanitari
🇮🇹
Trento, Italy
Centro Ricerche Cliniche Di Verona S.r.l.
🇮🇹
Verona, Italy
Istituto Auxologico Italiano
🇮🇹
Milan, Italy
Ospedale San Giovanni Bosco
🇮🇹
Turin, Italy
medius KLINIKEN gGmbH
🇩🇪
Kirchheim Unter Teck, Germany
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Hospital Universitario De Navarra
🇪🇸Pamplona, Spain
Francisco Javier Campano Lancharro
Site contact
+34848429850
francisco.campano.lancharro@navarra.es