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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Ns Pharma Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

6 Jun 2024 → ongoing

Decision date (initial)

2024-03-26

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2023-504245-32-00

ClinicalTrials.gov

NCT06046222

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Pharmacodynamic, Therapy, Efficacy

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 objectives 1

1. 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.

Conditions and MedDRA coding

Eosinophilic granulomatosis with polyangiitis (EGPA)

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. 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. 2) Male or female subjects aged ≥18 years at the time the informed consent form is signed
3. 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. 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.
5. 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 25

1. 1) Current diagnosis of either granulomatosis with polyangiitis or microscopic polyangiitis
2. 10) Parasitic infection: Subjects with a known parasitic infestation within 6 months prior to screening
3. 11) HIV-positive status
4. 12) Active hepatitis due to hepatitis B virus or hepatitis C virus
5. 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.
6. 14) Known history or presence of venous thromboembolism/venous thrombotic events
7. 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.
8. 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
9. 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)
10. 18) Subjects who are pregnant, breastfeeding, or planning to become pregnant during the time of study participation
11. 19) History of clinically significant drug or alcohol abuse within the last 6 months
12. 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
13. 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
14. 21) Current participation in any other interventional clinical study
15. 22) Unwilling or unable to comply with the protocol
16. 23) Suspected, probable, or confirmed diagnosis of active COVID-19
17. 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
18. 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.
19. 4) Serious liver, renal, blood, or psychiatric disease a) Moderate and severe hepatic impairment by the Child-Pugh scoring system
20. 5) Severe or clinically significant cardiovascular disease uncontrolled with standard treatment
21. 6) Electrocardiogram measurement of corrected QT by Fridericia >450 ms
22. 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
23. 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
24. 9) Active systemic infections
25. 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).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Primary Efficacy Endpoint: The proportion of subjects in remission (oral glucocorticoid [OGC] 4.0) at Week 28 of the study treatment period.
2. 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 endpoints 3

1. Secondary Efficacy Endpoints: The proportion of subjects in remission (OGC 7.5) at Week 28 of the study treatment period
2. Secondary Efficacy Endpoints: Time to first relapse of EGPA (active disease since the last visit after achieved decrease)
3. Secondary Efficacy Endpoints: Time to first worsening of EGPA (worsening of active disease since the last visit)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Ns Pharma Inc.

Sponsor organisation

Ns Pharma Inc.

Address

140 East Ridgewood Avenue Suite 280s

City

Paramus

Postcode

07652-3914

Country

United States

Scientific contact point

Organisation

Ns Pharma Inc.

Contact name

William R Pfister, PhD (Senior Director)

Public contact point

Organisation

Ns Pharma Inc.

Contact name

William R Pfister, PhD (Senior Director)

Third parties 5

Locations

4 EU/EEA countries · 10 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 87 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications