An Open Label Study of the Effects and Safety of Zanubrutinib in NMOSDs Adult Patients

• Status: Not yet recruiting
• Trial end date: 2024-10-01
• Target enrollment: 0
• Participant gender: All

Summary

This is an open-label study, to evaluate the efficacy and safety of a BTK inhibitor zanubrutinib in participants with NMOSDs.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Xuanwu Hospital, Beijing
• Treatments: Zanubrutinib

Criteria

Inclusion Criteria:

• Patients must meet the NMOSD diagnostic criteria set by the international NMO Diagnostic Group (IPND) in 2015.

• Serum AQP4-IgG positive.

• Clinical evidence of at least 2 documented relapse (including first attack) in the last 2 years, with at least 1 relapse within 12 months prior to screening.

• Extended Disability Status Scale (EDSS) score ≤7.5 at screening.

• Age 18 to 75 years inclusive, weight at least 35 kg at the time of informed consent.

• If the patients were using the following baseline treatment for relapse prevention, they must be treated at a steady dose for at least 4 weeks prior to enrollment:

• Azathioprine, metecophenol ester and other immunosuppressive agents

• Oral corticosteroid (≦30mg/ day prednisone tablet or equivalent dose of other hormones)

• (patients or their legal representatives) can provide written informed consent indicating that they understand and agree to comply with the requirements of the study protocol.

Exclusion Criteria:

• Continuous treatment with strong or moderate CYP3A inhibitors or inducers is required during the study period. Patients were excluded if they had taken a potent or moderate CYP3A inhibitor or inducer within 7 days prior to administration of the study drug (or had stopped taking these drugs for less than 5 half-lives).

• Previously treated with BTK inhibitors (e.g., ibrutinib).

• Allergic to the study drug or any of the ingredient.

• Desease relaps (including first episode) within the previous 30 days.

• Pregnancy or lactation.

• Previous or current malignancy, except locally recurrent cancers that have received radical treatment (e.g. excised basal or squamous cell skin cancer, cervical or breast cancer in situ).

• Currently central nervous system (CNS) disease that may affect the evaluation of NMOSD.

• Serious and uncontrolled conditions considered by the investigator that could affect safety, compliance and endpoint evaluation, or need for use of a drug not permitted in the protocol.

• Disease that could affected drug absorption, distribution, metabolism, and excretion determined by the investigator.

• Any major clinical infection lead to hospitalization or parenteral antibiotic treatment within 1 month prior to screening; Or other infections that may be aggravated due to the study determined by the investigator.

• Active, latent or undertreated mycobacterium tuberculosis (TB) infection

• Known primary immunodeficiency or underlying disease such as human immunodeficiency virus (HIV) infection.

• Hepatitis B or C virus infection by serological test.

• Received B-cell targeted therapy (e.g. Rituximab) within 6 months prior to the initial administration of the study drug.

• Received biologics such as tozizumab within 12 weeks prior to initial administration of the study drug.

• Received live attenuated vaccine during the screening and study periods, or any live virus vaccine within 8 weeks prior to initial administration.

• Abnormal and clinically significant in ECG examination during screening.

• Uncontrolled hypertension (SBP>160 mmHg or DBP ≥ 95 mmHg)

• Grade 3 or 4 heart Failure, (NYHA scale).

• Severe liver insufficiency (Child-pugh C).

• Aspartate aminotransferase (AST)>3 times the upper limit of normal (ULN) and/or alanine aminotransferase (ALT)>3ULN and/or bilirubin >2ULN.

• Estimated creatinine clearance <30 mL/min or requiring dialysis.

• Inability to receive MRI scans

• A history of clinically significant CNS trauma

• Received experimental drug or other experimental treatment within 4 weeks prior to screening or during 5 pharmacokinetic half-lives or duration of biological effects, whichever is longer.

• Participate in another clinical study.

• Accept any of the following:

• BCG vaccination within 1 year prior to screening.

• Prior bone marrow transplant, hematopoietic stem cell transplant, or systemic radiation therapy.

• Received intravenous gamma globulin within 30 days prior to screening.

• Plasmapheresis or leukocyte separation within 90 days prior to screening

• Abnormal white blood cell count, neutrophil count, lymphocyte count, or platelet count during the screening and were considered unsuitable for study by investigator

• Inability to swallow capsules or medical conditions that significantly affect gastrointestinal function

• A history of severe hemorrhagic disorders such as hemophilia A, hemophilia B, von willebrand disease, or a history of spontaneous bleeding requiring blood transfusion or other medical intervention.

• History of stroke or intracranial hemorrhage within 6 months prior to screening

• Current alcohol, drug or chemical abuse, or history of such abuse within 1 year prior to screening.

• Anticoagulants or a combination of anticoagulants and antiplatelet agents is ongoing or planned.

• Any other circumstances in which the investigator or sponsor considers the patient unsuitable for study participation.