- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05356858
An Open Label Study of the Effects and Safety of Zanubrutinib in NMOSDs Adult Patients
May 15, 2022 updated by: Xuanwu Hospital, Beijing
An Open Label Trial Evaluating the Efficacy and Safety of Bruton's Tyrosine Kinase (BTK) Inhibitor Zanubrutinib in Adult Patients With Neuromyelitis Optical Spectrum Disorders (NMOSDs)
This is an open-label study, to evaluate the efficacy and safety of a BTK inhibitor zanubrutinib in participants with NMOSDs.
Study Overview
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 diagnosed with neuromyelitis optic spectrum disease according to the NMOSD diagnostic criteria established by the international NMO Diagnostic Group (IPND) in 2015, and to have had at least two relapses (including first episode) within two years while at least one relapse occurring within the 12 months prior to screening.
The AQP4 antibody must be positive during screening.
Study Type
Interventional
Enrollment (Anticipated)
20
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Junwei Hao, MD
- Phone Number: 86-10-83922345
- Email: lzwcy2003@aliyun.com
Study Contact Backup
- Name: Zheng Liu, MD
- Phone Number: 86-10-83922345
- Email: lzwcy2003@aliyun.com
Study Locations
-
-
Beijing
-
Beijing, Beijing, China, 100053
- Recruiting
- Xuanwu Hospital
-
Contact:
- Zheng Liu, MD
- Phone Number: 010-83922345
- Email: lzwcy2003@aliyun.com
-
Contact:
- Tao Wu, MD
- Phone Number: 010-83922345
- Email: wu835148631@163.com
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 75 years (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: zanubrutinib
zanubrutinib orally, 80mg bid for 1 year
|
zanubrutinib orally, 80mg bid for 1 year
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Relapse-free rate at week 48
Time Frame: up to week 48
|
Proportion of subjects who are relapse-free at week 48
|
up to week 48
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Changes in the expanded disability status scale (EDSS) score from baseline at week 12,24,36 and 48
Time Frame: up to week12,24,36 and 48
|
EDSS is an ordered scale with values ranging from 0 points (normal neurological examination) to 10 points (death) in increments of 0.5 points.
Higher scores indicate increased disability, and negative changes from baseline indicate improvement
|
up to week12,24,36 and 48
|
Changes in visual acuity at week 12, 24,36 and 48 from baseline
Time Frame: up to week12,24,36 and 48
|
Changes in visual acuity at week 12, 24,36 and 48 from baseline
|
up to week12,24,36 and 48
|
Changes in the MOS item short from health survey (SF-36) score at week 12, 24,36 and 48 from baseline
Time Frame: up to week12,24,36 and 48
|
The SF-36 is a multi-purpose, concise 36-question health survey scale.
It contains 8 dimensions,The eight dimensions were converted to a scale of 0-100, with a higher score indicating a better quality of life.
Positive change from baseline indicates improvement.
|
up to week12,24,36 and 48
|
Changes in Serum AQP4-IgG titer at week 12, 24,36 and 48 from baseline
Time Frame: up to week12,24,36 and 48
|
Changes in Serum AQP4-IgG titer at week 12, 24,36 and 48 from baseline
|
up to week12,24,36 and 48
|
Changes in Peripheral blood lymphocyte subset at week 12, 24,36 and 48 from baseline
Time Frame: up to week12,24,36 and 48
|
Changes in Peripheral blood lymphocyte subset at week 12, 24,36 and 48 from baseline
|
up to week12,24,36 and 48
|
Plasma concentraion of zanubrutinib
Time Frame: up to week 48
|
Concentraion of zanubrutinib in peripheral blood plasma
|
up to week 48
|
Number of participants with all grade Adverse Events, Serious Adverse Events and who discontinued study therapy due to AEs
Time Frame: up to week 48
|
Evaluate Number of participants with all grade Adverse Events and Serious Adverse Events determined by NCI-CTCAE V5.0,and tolerance base on percentage of patients who discontinued study therapy due to AEs
|
up to week 48
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Concentraion of zanubrutinib in Cerebrospinal fluid at week 12
Time Frame: up to week 12
|
Concentraion of zanubrutinib in Cerebrospinal fluid at week 12
|
up to week 12
|
BTK accupancy of peripheral blood mononuclear cells
Time Frame: up to week 48
|
BTK accupancy of peripheral blood mononuclear cells in NMOSD patients before zebutinib administration, 4-6h after zebutinib administration, and at weeks 12 and 48.
|
up to week 48
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Chair: Junwei Hao, MD, Xuanwu Hospital, Beijing
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (ACTUAL)
May 7, 2022
Primary Completion (ANTICIPATED)
October 1, 2024
Study Completion (ANTICIPATED)
October 1, 2024
Study Registration Dates
First Submitted
April 26, 2022
First Submitted That Met QC Criteria
April 26, 2022
First Posted (ACTUAL)
May 2, 2022
Study Record Updates
Last Update Posted (ACTUAL)
May 20, 2022
Last Update Submitted That Met QC Criteria
May 15, 2022
Last Verified
April 1, 2022
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Nervous System Diseases
- Immune System Diseases
- Demyelinating Autoimmune Diseases, CNS
- Autoimmune Diseases of the Nervous System
- Demyelinating Diseases
- Autoimmune Diseases
- Eye Diseases
- Optic Nerve Diseases
- Cranial Nerve Diseases
- Myelitis, Transverse
- Optic Neuritis
- Neuromyelitis Optica
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Protein Kinase Inhibitors
- Zanubrutinib
Other Study ID Numbers
- BGB-3111-2005-IIT
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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