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

• Status: Not yet recruiting
• Trial end date: 2023-08-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Peking Union Medical College Hospital
• Collaborators: Beijing InnoCare Pharma Tech Co., Ltd.; GCP ClinPlus Co., Ltd.

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.