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A Study of Orelabrutinib in Patients With AQP4-IgG Positive Neuromyelitis Optica Spectrum Disorder

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05284175
Recruitment Status : Not yet recruiting
First Posted : March 17, 2022
Last Update Posted : March 17, 2022
Sponsor:
Collaborators:
Beijing InnoCare Pharma Tech Co., Ltd.
GCP ClinPlus Co., Ltd.
Information provided by (Responsible Party):
Yan Xu, Peking Union Medical College Hospital

Brief Summary:
Neuromyelitis optica spectrum disorder (NMOSD) is a chronic inflammatory demyelinating autoimmune disease of the central nervous system. NMOSD is a highly relapsing, severely disabling disease. AQP4-IgG positive NMOSD is related to a specific aquaporin 4 antibody (AQP4 IgG) produced by mature B cells. BTK is a key kinase in B cell receptor signal transduction pathway. Abnormal activation of BTK related signaling pathway can lead to autoantibody production and autoimmune diseases. Therefore, BTK can be developed as a new target for autoimmune diseases.

Condition or disease Intervention/treatment Phase
Neuromyelitis Optica Spectrum Disorder Drug: Orelabrutinib Not Applicable

Detailed Description:

Approximately 23 subjects will be enrolled.

Experimental drug treatment: Orelabrutinib, 50mg, orally, once a day.

The subject will come to visit at week 0, 1, 2, 4, 8, 12, 16, 20, 24, 36, 48 and safety follow up visit which is planed 28 days after last administration.

Baseline patient assessment:

  1. Baseline examination: vital signs, physical examination, blood routine examination, urine routine examination, liver and kidney function, coagulation function, thyroid function, HIV, HCV, HBV virus test, tuberculosis test, chest X-ray, ECG and pregnancy test.
  2. Functional disability assessment: Expanded Disability Status Scale (EDSS) score and low contrast vision (LCVA) score.
  3. EQ5D scale evaluation.
  4. Serum AQP4-IgG titer, neuro filament light chain, T/B/NK cell count, Immunoglobulin (IgG, IgA and IgM)

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 23 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Prospective, Self-controlled Study to Explore Efficacy and Safety of Orelabrutinib in AQP4-IgG Positive Neuromyelitis Optica Spectrum Disorder
Estimated Study Start Date : April 2022
Estimated Primary Completion Date : August 2023
Estimated Study Completion Date : August 2023


Arm Intervention/treatment
Experimental: Orelabrutinib, orally, 50 mg QD
Orelabrutinib, orally, 50 mg QD
Drug: Orelabrutinib
Orelabrutinib, orally, 50 mg QD




Primary Outcome Measures :
  1. Annualized relapse rate at week 48 compared with that before baseline. [ Time Frame: week 48 ]
    Annualized relapse rate at week 48 compared with that before baseline.


Secondary Outcome Measures :
  1. Proportion of patients without relapse [ Time Frame: weeks 24 and 48 ]
    Proportion of patients without relapse at weeks 24 and 48;

  2. Changes in the expanded disability status scale (EDSS) score from baseline [ Time Frame: weeks 4, 12, 24, 36 and 48 ]
    Changes in the expanded disability status scale (EDSS) score from baseline at weeks 4, 12, 24, 36 and 48;

  3. Changes in low contrast visual acuity score (LCVA) from baseline [ Time Frame: weeks 4, 12, 24, 36 and 48 ]
    Changes in low contrast visual acuity score (LCVA) from baseline at weeks 4, 12, 24, 36 and 48;

  4. Changes in EQ5D scores from baseline [ Time Frame: weeks 12, 24, 36 and 48 ]
    Changes in EQ5D scores from baseline at weeks 12, 24, 36 and 48;

  5. Changes in serum AQP4-IgG titer and neurofilament light chain protein level from baseline [ Time Frame: weeks 4, 12, 24, 36 and 48 ]
    Changes in serum AQP4-IgG titer and neurofilament light chain protein level from baseline at weeks 4, 12, 24, 36 and 48;

  6. Changes in absolute value of peripheral blood B cell count and immunoglobulin (IgA, IgM, IgG) from baseline [ Time Frame: weeks 4, 12, 24, 36 and 48 ]
    Changes in absolute value of peripheral blood B cell count and immunoglobulin (IgA, IgM, IgG) at weeks 4, 12, 24, 36 and 48 from baseline;

  7. Percentage of patients who withdraw from the study due to adverse events. [ Time Frame: weeks1, 2, 4, 8, 12, 16, 20, 24, 36 , 48 ]
    Percentage of patients who withdraw from the study due to adverse events.



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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 1) 18-75 years old (inclusive) at the time of signing the informed consent form
  • 2)Diagnosed with AQP4-IgG positive NMOSD in accordance with 2015 IPND diagnostic criteria.
  • 3)Relapse ≥ 2 within 1 year before screening, and at least 1 relapse within 6 months before screening
  • 4)If the subject has stable steroids treatment (≤ 7.5mg prednisone, or equivalent dose of steroids), the treatment needs to be stable more than 1 month before starting the study drug treatment.
  • 5)EDSS ≤7.5 at screening
  • 6)Negative pregnancy test for female of childbearing potential at screening
  • 7)Understood the study procedure and voluntarily signed written informed consent

Exclusion Criteria:

  • 1) History of serious heart, lung, liver, kidney, blood disease, etc.
  • 2) Any major infection judged by the investigator requiring hospitalization and parenteral antimicrobial treatment within 1 month before screening
  • 3) History of episodes of herpes zoster ≥ 2 or disseminated herpes zoster ≥ 1
  • 4) History of or having any of the following medication / treatment: ① Received BTK inhibitor at any time in the past; ② B-cell targeted therapy within 12 weeks before the first dose; ③ Received biological agents within 12 weeks before the first dose; ④ Received live virus vaccine or live attenuated vaccine within 8 weeks before the first dose; ⑤ Received steroids treatment for other diseases within 6 months before screening, the dosage > 20mg / day for more than 21 days; ⑥ Used a study drug or other experimental treatment within 4 weeks before screening or 5 half-lives, or participating in any other intervention clinical trial.
  • 5) During screening or baseline examination, laboratory results meet the exclusion criteria:

    • Human immunodeficiency virus (HIV) positive
    • Hepatitis C virus (HCV) antibody positive. (If a subject has a history of HCV infection, has completed and recorded appropriate treatment at least 1 year before screening, and the HCV RNA measured by PCR at the time of screening is negative, the subject will not be excluded from this study.)
    • Hepatitis B surface antigen (HBsAg) positive and / or hepatitis B core antibody (HBcAb) positive
    • Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2
    • ALT/AST > 2 x ULN, Total Bilirubin > 1.5 x ULN, or any other clinically significant laboratory abnormality
    • Neutrophil < 1500 / mm3, platelet < 75000 / mm3, lymphocyte < 1000 / mm3 or leukocyte < 3500 / mm3.
    • International standardized ratio (INR) ≥ 1.5 or activated partial thromboplastin time (APTT) ≥ 1.5x ULN.
    • CD19 B cells lower than the lower limit of the normal range
  • 6) Used strong to medium CYP3A inducers within 3 weeks before treatment, or strong to medium CYP3A inhibitors within 1 week before treatment, or strong to medium CYP3A inducers or inhibitors may be used during treatment.
  • 7) There are situations that other researchers think are not suitable to participate in this study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05284175


Contacts
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Contact: Yan Xu, Doctor 18601355218 xuyanpumch@hotmail.com

Locations
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China, Beijing
Peking Union Medical College Hospital, Chinese Academy of Medical Sciences
Beijing, Beijing, China, 100730
Contact: Yan Xu, Dr.    18601355218    xuyanpumch@hotmail.com   
Sponsors and Collaborators
Peking Union Medical College Hospital
Beijing InnoCare Pharma Tech Co., Ltd.
GCP ClinPlus Co., Ltd.
Investigators
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Principal Investigator: Yan Xu, Doctor Peking Union Medical College
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Responsible Party: Yan Xu, Chief Physician, Peking Union Medical College Hospital
ClinicalTrials.gov Identifier: NCT05284175    
Other Study ID Numbers: ICP-022-006
First Posted: March 17, 2022    Key Record Dates
Last Update Posted: March 17, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Yan Xu, Peking Union Medical College Hospital:
Neuromyelitis Optica Spectrum Disorder
BTK inhibitors
Orelabrutinib
Additional relevant MeSH terms:
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Neuromyelitis Optica
Disease
Pathologic Processes
Myelitis, Transverse
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Optic Neuritis
Optic Nerve Diseases
Cranial Nerve Diseases
Demyelinating Diseases
Eye Diseases
Autoimmune Diseases
Immune System Diseases