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

NCT05284175 | Unknown

• 1 other identifier: ICP-022-006
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

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.

Conditions

Neuromyelitis Optica Spectrum Disorder

Keywords

Neuromyelitis Optica Spectrum Disorder; BTK inhibitors; Orelabrutinib

Outcome Measures

Primary Outcomes (1)

• Annualized relapse rate at week 48 compared with that before baseline.

  Annualized relapse rate at week 48 compared with that before baseline.

  week 48

Secondary Outcomes (7)

• Proportion of patients without relapse

  weeks 24 and 48

• Changes in the expanded disability status scale (EDSS) score from baseline

  weeks 4, 12, 24, 36 and 48

• Changes in low contrast visual acuity score (LCVA) from baseline

  weeks 4, 12, 24, 36 and 48

• Changes in EQ5D scores from baseline

  weeks 12, 24, 36 and 48

• Changes in serum AQP4-IgG titer and neurofilament light chain protein level from baseline

  weeks 4, 12, 24, 36 and 48

Study Arms (1)

Orelabrutinib, orally, 50 mg QD

EXPERIMENTAL

Orelabrutinib, orally, 50 mg QD

Drug: Orelabrutinib

Interventions

Orelabrutinib DRUG

Orelabrutinib, orally, 50 mg QD

Orelabrutinib, orally, 50 mg QD

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \) 18-75 years old (inclusive) at the time of signing the informed consent form
• )Diagnosed with AQP4-IgG positive NMOSD in accordance with 2015 IPND diagnostic criteria.
• )Relapse ≥ 2 within 1 year before screening, and at least 1 relapse within 6 months before screening
• )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.
• )EDSS ≤7.5 at screening
• )Negative pregnancy test for female of childbearing potential at screening
• )Understood the study procedure and voluntarily signed written informed consent

You may not qualify if:

• \) History of serious heart, lung, liver, kidney, blood disease, etc.
• \) Any major infection judged by the investigator requiring hospitalization and parenteral antimicrobial treatment within 1 month before screening
• \) History of episodes of herpes zoster ≥ 2 or disseminated herpes zoster ≥ 1
• \) 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.
• 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
• \) 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.
• \) There are situations that other researchers think are not suitable to participate in this study.

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead
• Beijing InnoCare Pharma Tech Co., Ltd.: collaborator
• GCP ClinPlus Co., Ltd.: collaborator

Study Sites (1)

Peking Union Medical College Hospital, Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, 100730, China

Location

MeSH Terms

Conditions

Neuromyelitis Optica

Interventions

orelabrutinib

Condition Hierarchy (Ancestors)

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

Study Officials

• Yan Xu, Doctor

  Peking Union Medical College

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yan Xu, Doctor

CONTACT

18601355218; xuyanpumch@hotmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: March 9, 2022
• First Posted: March 17, 2022
• Study Start: April 1, 2022
• Primary Completion: August 1, 2023
• Study Completion: August 1, 2023
• Last Updated: March 17, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)