Efficacy and Safety of Baricitinib in Neuromyelitis Optica Spectrum Disorders

Study Overview
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Brief Summary
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Neuromyelitis Optica Spectrum Disorders (NMOSD) is associated with a pathological humoral immune response against the aquaporin-4(AQP-4) water channel. Baricitinib is an oral Janus kinase (JAK)1/JAK2 inhibitor that blocks the upregulated JAK-STAT pathway in patients with neuroimmune disorders, which is important in bone marrow regulation of B cell proliferation and differentiation. Baricitinib may benefit some patients with NMOSD due to the important role of B cells in the pathogenesis of NMOSD. Clincial trials may be needed to observe its efficacy and safety.

Detailed Description
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The investigators primarily aim to observe the time to first relapse from initiation of baricitinib treatment. The secondary outcomes are to determine: The safety profile of baricitinib in participants with NMO and whether baricitinib improves Expanded Disability Status Scale (EDSS), et al.

Official Title
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Efficacy and Safety of Baricitinib in Neuromyelitis Optica Spectrum Disorders

Conditions
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NMO Spectrum Disorder

Intervention / Treatment
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* Drug: Baricitinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients ≥ 18 years old; Diagnosis of NMO or NMO spectrum disorder according to the 2015 International diagnostic criteria for neuromyelitis optic; Clinical evidence of either at least one attack requiring rescue therapy (intravenous corticosteroids,intravenous immunoglobulin,plasma exchange,or a combination of these therapies) or at least two attacks requiring rescue therapy in the 2 years before screening; EDSS <=6.0; Able and willing to give written informed consent and comply with the requirements of the study protocol. Exclusion Criteria: Current evidence or known history of clinically significant infection (Herpes simplex virus, varicella-zoster virus, cytomegalovirus, Epstein-Barr virus, human immunodeficiency virus, Hepatitis viruses, Syphilis, etc); Participation in another interventional trial within the last 3 months Tumor disease currently or within last 5 years; Pregnant, breastfeeding, or child-bearing potential during the course of the study Clinically relevant heart, liver, kidney or bone marrow function disorder.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Baricitinib<br>Baricitinib will be taken orally with a dose of 2mg once daily until the disease relapses or week 48, with a final evaluation at week 52. | Drug: Baricitinib<br>* Baricitinib will be taken orally with a dose of 4mg once daily until the disease relapses or week 48, with a final evaluation at week 52.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| First time to relapse | An acute attack was defined as a new neurological worsening lasting for at least 24 hours and occurring more than 30 days after the previous attack | From baseline to one year after | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in EDSS | The Expanded Disability Status Scale (EDSS) is a rating system that is frequently used for classifying and standardizing the severity and progression. EDSS ranges from 0 to 10. | Changes in EDSS from baseline to 52 weeks | 
| Changes in the number of New, and/or Enlarging T2 Hyperintense Lesions as Detected by Optic nerve,brain and spinal cord Magnetic Resonance Imaging (MRI) | The total number of new and/or enlarging T2 lesions for all participants was calculated as the sum of the individual number of lesions at Weeks 12, 24, and 52 | From baseline to 52 weeks | 
| Changes in peripheral blood B cell subsets | Compare peripheral blood plasma cells before and one year after initial intervention | From baseline to 52 weeks | 
| Changes in serum AQP4 antibodies | Compare serum AQP4-ab titers before and one year after initial intervention | From baseline to 52 weeks | 
| Incidence of treatment-emergent adverse events [safety and tolerability] | Adverse events related to belimumab are recorded | From baseline to 52 weeks |