Efficacy and Safety of Belimumab 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. Belimumab (Benlysta ®) is a human immunoglobulin G1λ monoclonal antibody that inhibits B-cell survival and differentiation by neutralizing soluble B lymphocyte stimulator. Belimumab 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 belimumab treatment. The secondary outcomes are to determine: The safety profile of belimumab in participants with NMO and whether belimumab improves Expanded Disability Status Scale (EDSS), et al.

Official Title
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Efficacy and Safety of Belimumab in Neuromyelitis Optica Spectrum Disorders (BEAT NMO)

Conditions
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NMO Spectrum Disorder

Intervention / Treatment
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* Drug: Belimumab


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

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Belimumab<br>Belimumab will be intravenously administered with a dose of 10mg/kg on Days 0,14 and28, then every 28 days until week 48, with a final evaluation at week 52. | Drug: Belimumab<br>* Belimumab will be intravenously administered with a dose of 10mg/kg on Days 0,14 and28, then every 28 days until 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 |
| --- | --- | --- |
| Worsening 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. | Worsening from baseline in EDSS to 52 weeks | 
| 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 | 
| Counts of peripheral blood B cell subsets | Compare peripheral blood plasma cells before and one year after initial intervention | From baseline to 52 weeks | 
| Determination of 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 |