Rituximab at Low dosE for neuromyelitiS optiCa spectrUm disordEr (RESCUE)

Study Overview
=================
Brief Summary
-----------------
In this research, a prospective, multicenter(Tangdu Hospital of Fourth Military Medical University, Xi'an Gaoxin Hospital of Xi'an Medical College, Xianyang Central Hospital, Baoji Central Hospital, Xi'an Central Hospital, The First Hospital of Xi'an, The Fourth Hospital of Xi'an) open-label, follow-up clinical trial will carry out to evaluate the efficacy and safety of low-dose rituximab in treating NMOSD in Northwest China.

Detailed Description
-----------------
Neuromyelitis optica spectrum disorder (NMOSD) is a group of autoimmune inflammatory demyelinating disease of the central nervous system primarily characterized with recurrent optic neuritis and longitudinally extensive transverse myelitis, leading to blindness and paralysis. Incremental disability due to clinical attacks make it essential to prevent relapses with immunosuppressive therapy. Since the serological pathogenic marker anti-aquaporin 4 immunoglobulin G (anti-AQP4 IgG) has been identified, NMOSD has unveiled its autoimmune features with close connections to B cell-mediated humoral immunity. Rituximab, a chimeric monoclonal antibody directly against human CD20 molecular on the surface of B cells, has been reported to deplete peripheral CD20+ B cells and to be highly effective for treating NMOSD, and therefore been recommended as first-line therapy for this disorder. Unfortunately, there are still no consensus statements on dosing and follow-up regimens, which needs investigations to explore the efficacy and safety of different rituximab strategies. Previous studies have provided pilot evidence supporting the use of low-dose rituximab in preventing relapses in Chinese patients with NMO/NMOSD, however, prospective multicenter studies are still needed to determine the effectiveness of the modified strategy in treating NMOSD.

Official Title
-----------------
Rituximab at Low dosE for neuromyelitiS optiCa spectrUm disordEr (RESCUE): a Prospective, Multicenter, Open-label, Follow-up Clinical Trial

Conditions
-----------------
Neuromyelitis Optica Spectrum Disorder

Intervention / Treatment
-----------------
* Drug: Rituximab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age between 16 and 75 years old; Meet the 2007 or 2015 revised diagnostic criteria for NMOSD; At least two relapses in recent two years and/or at least one attack or relapse in recent one years; Expanded disability status scale (EDSS) score ≤7.0; Willingness to sample collection, imaging study and other disease-related examinations and assessments; Results of pregnancy tests for female patients with fertility during the screening period should be negative and effective contraception was used by the patient and her spouse during the study period; Patients with informed consent. Exclusion Criteria: Other immunosuppressive agents are being used or have been discontinued for less than 3 months; White blood cell count (WBC) <3 ×109/L, neutrophil count <1.5 ×109/L, hemoglobin (HGB) < 85 g/L, and platelet count (PLT) < 80×109/L; Concomitant active liver disease or persistent elevation of transaminases more than three times above the normal upper limit; Serious cardiovascular, kidney, blood and endocrine diseases, or history of malignant tumors, or severe infection; Other chronic active immune diseases or stable conditions but requiring immunosuppressants or glucocorticoids, such as rheumatoid arthritis, scleroderma, Sjögren's syndrome, ulcerative colitis, AIDS, genetic or drug-induced immune deficiency; Pregnant or lactating patients and those with family planning during the study period; Allergy to rituximab and other components; Inability to provide informed consent.

Ages Eligible for Study
-----------------
Minimum Age: 16 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rituximab<br>Intravenous rituximab was administered at a fixed dose of 100 mg once weekly for 3 weeks, followed by maintenance treatment with 100 mg rituximab every 6 months. | Drug: Rituximab<br>* A scheduled therapeutic regimen with low-dose rituximab was performed.<br>* Other names: Rituxan;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized relapse rate at last follow-up visit | All the enrolled patients are followed up and annualized relapse rate is determined at last follow-up visit. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Expanded disability status scale (EDSS) score at last follow-up visit | All the enrolled patients are followed up and expanded disability status scale (EDSS) score is determined at last follow-up visit. In general, the minimum and maximum scores of EDSS are 0 and 10, respectively, with higher scores meaning a worse outcome. | 12 months | 
| Rituximab-related adverse events | Rituximab-related adverse events (AEs) are evaluated and the rate of AEs is recorded. | 1 month, 3 months, 6 months, 9 months, 12 months | 
| Lesions in spinal cords | Changes of lesions in spinal cord were evaluated by MRI scanning. | 6 months, 12 months | 
| Circulating B cell monitoring | Frequencies of total B cell (CD19+) and memory B cell (CD19+CD27+) in lymphocytes were assessed by flow cytometry. | 6 months, 12 months | 
| Switch treatment | Other immunosuppressive agents switched from rituximab and reasons for the switch are recorded. | 6 months, 12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Neuromyelitis Optica Spectrum Disorder, Rituximab