METHYL-(1-{[6-{[(1S)-1-CYCLOPROPYLETHYL]AMINO}-2-(PYRAZOLO[5,1-B][1,3]THIAZOL-7-YL)-PYRIMIDIN-4-YL]CARBONYL}PIPERIDIN-4-YL)CARBAMATE-MONO(4-METHYLBENZENESULFONATE) MONOHYDRATE for Eosinophilic granulomatosis with polyangiitis

Inclusion criteria

• {"criterion_text":"- 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\n- 2) Male or female subjects aged ≥18 years at the time the informed consent form is signed\n- 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\n- 4) 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.\n- 5) 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

• {"criterion_text":"- 1) Current diagnosis of either granulomatosis with polyangiitis or microscopic polyangiitis\n- 18) Subjects who are pregnant, breastfeeding, or planning to become pregnant during the time of study participation\n- 19) History of clinically significant drug or alcohol abuse within the last 6 months\n- 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\n- 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\n- 21) Current participation in any other interventional clinical study\n- 22) Unwilling or unable to comply with the protocol\n- 23) Suspected, probable, or confirmed diagnosis of active COVID-19\n- 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\n- 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.\n- 4) Serious liver, renal, blood, or psychiatric disease a) Moderate and severe hepatic impairment by the Child-Pugh scoring system\n- 10) Parasitic infection: Subjects with a known parasitic infestation within 6 months prior to screening\n- 5) Severe or clinically significant cardiovascular disease uncontrolled with standard treatment\n- 6) Electrocardiogram measurement of corrected QT by Fridericia >450 ms\n- 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\n- 8) 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\n- 9) Active systemic infections\n- 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).\n- 11) HIV-positive status\n- 12) Active hepatitis due to hepatitis B virus or hepatitis C virus\n- 13) 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.\n- 14) Known history or presence of venous thromboembolism/venous thrombotic events\n- 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 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.\n- 16) 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\n- 17) 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)"}

Primary endpoints

• {"endpoint_text":"- Primary Efficacy Endpoint: The proportion of subjects in remission (oral glucocorticoid [OGC] 4.0) at Week 28 of the study treatment period.","definition_or_measurement_approach":"Proportion of subjects meeting remission definition (oral glucocorticoid [OGC] 4.0) at Week 28 of the study treatment period (measured as the proportion of randomized subjects in remission at Week 28)."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Count and characterization of adverse events (AEs), including treatment-related and severe reactions, collected over the study period."}

Secondary endpoints

• {"endpoint_text":"- Secondary Efficacy Endpoints: The proportion of subjects in remission (OGC 7.5) at Week 28 of the study treatment period","definition_or_measurement_approach":"Proportion of subjects in remission defined as OGC 7.5 at Week 28."}
• {"endpoint_text":"- Secondary Efficacy Endpoints: Time to first relapse of EGPA (active disease since the last visit after achieved decrease)","definition_or_measurement_approach":"Time-to-event measurement: time from randomization (or from remission) to first relapse of EGPA, defined as active disease since last visit after prior decrease."}
• {"endpoint_text":"- Secondary Efficacy Endpoints: Time to first worsening of EGPA (worsening of active disease since the last visit)","definition_or_measurement_approach":"Time-to-event measurement: time from randomization to first documented worsening of EGPA (worsening of active disease since last visit)."}

Methods

• Banner ads (online) — documents titled "K2_Banner ads patient" / "K2_Recruitment material_Banner ads" indicate use of banner advertising targeted to patients.
• Google ads / search keywords — documents titled "K2_Google ads keywords" / "K2_Recruitment material_Google ads keywords" indicate use of paid search/Google ads targeting patient queries.
• Social media ads/posts — documents titled "K2_Social media ads_Redacted" / "K2_Recruitment material_Social media posts" indicate use of social media channels for patient recruitment.
• Patient brochure / study materials — documents titled "K2_Patient brochure" / "K2_Recruitment material_Patient brochure" and study visit guides indicate distribution of informational brochures to potential participants.

France

Earliest CTIS Part Ii Submission Date

28-02-2024

Latest Decision Or Authorization Date

31-01-2025

Processing Time Days

338

Number Of Sites

3

Number Of Participants

5

Germany

Earliest CTIS Part Ii Submission Date

13-03-2024

Latest Decision Or Authorization Date

13-03-2025

Processing Time Days

365

Number Of Sites

1

Number Of Participants

1

Italy

Earliest CTIS Part Ii Submission Date

26-01-2024

Latest Decision Or Authorization Date

29-01-2025

Processing Time Days

369

Number Of Sites

5

Number Of Participants

7

Spain

Earliest CTIS Part Ii Submission Date

01-03-2024

Latest Decision Or Authorization Date

30-01-2025

Processing Time Days

336

Number Of Sites

2

Number Of Participants

7

Primary sponsor

Full Name

Ns Pharma Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Third parties

• {"country":"United States","full_name":"Syneos Health Inc.","duties_or_roles":"sponsorDuties codes: 1,10,11,12,13,2,5,6,7,8","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"PPD Global Central Labs","duties_or_roles":"Central Lab EU (sponsorDuties code 15) and code 4","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"eResearchTechnology GmbH","duties_or_roles":"Respiratory (sponsorDuties value 15)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"IVRS/IWRS (sponsorDuties value 15)","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"eCOA, Cardiac Safety (sponsorDuties value 15)","organisation_type":"Pharmaceutical company"}