Status:

UNKNOWN

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

Lead Sponsor:

Xuanwu Hospital, Beijing

Conditions:

Neuromyelitis Optica

Eligibility:

All Genders

18-75 years

Phase:

PHASE2

Brief Summary

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

Detailed Description

This is an open, single-center clinical study to evaluate the efficacy and safety of Zanubrutinib in the treatment of recurrent neuromyelitis optica spectrum disease. Patients were required to be diag...

Eligibility Criteria

Inclusion

  • 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

  • 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.

Key Trial Info

Start Date :

May 7 2022

Trial Type :

INTERVENTIONAL

Allocation :

ESTIMATED

End Date :

October 1 2024

Estimated Enrollment :

20 Patients enrolled

Trial Details

Trial ID

NCT05356858

Start Date

May 7 2022

End Date

October 1 2024

Last Update

May 20 2022

Active Locations (1)

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XuanWu Hospital

Beijing, Beijing Municipality, China, 100053

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