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Inebilizumab and Rituximab in Neuromyelitis Optica Spectrum Disorders

Not yet recruiting
Conditions
Neuromyelitis Optica Spectrum Disorders
Interventions
Drug: Rituximab(RTX)
Registration Number
NCT06068829
Lead Sponsor
Feng Jinzhou
Brief Summary

To compare the safety and efficacy of Inebilizumab and Rituximab in neuromyelitis optica spectrum disorders (NMOSD) patients.

Detailed Description

Inebilizumab is a humanized anti-CD19 monoclonal antibody. CD19 is broadly expressed on B-lineage cells, particularly late-stage memory B-lymphocytes and plasma blasts. Inebilizumab depletes antibody-secreting plasmablasts and some plasma cells.

Rituximab (RTX) is a chimeric anti-CD20 monoclonal antibody that promotes B-lymphocyte depletion through antibody-dependent cellular cytotoxicity (ADCC)/complement-dependent cytotoxicity (CDC), promotes an immunoregulatory T-lymphocyte phenotype, and activates neutrophil/macrophage phagocytosis.

This is a retrospective, multicentre, real-world study which aims to compare Inebilizumab with RTX in neuromyelitis optica spectrum disorders patients. Eighty patients from 8 centres in China will be enrolled.

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
80
Inclusion Criteria
    1. Age ≥ 18 years with anti-AQP4-IgG seropositive NMOSD as defined by 2015 NMOSD diagnostic criteria by IPND (International Panel for NMO Diagnosis).
    1. Expanded disability status scale (EDSS) score ≤ 8 and ≥ 2.5 during the acute phase.
    1. Patients have given their written informed consent.
Exclusion Criteria
    1. Lactating and pregnant females.
    1. Participate in other interventional studies within 30 days or within 5 half-lives of the investigational agent before received inebilizumab and rituximab (RTX).
    1. Receipt of any experimental B-cell depleting agent within 6 months prior inebilizumab and RTX, and B-cells below the lower limit of normal
    1. Known history of a severe allergy or reaction to any component of the investigational product formulation.
    1. Known active severe bacterial, viral, or other infection or any major episode of infection requiring hospitalization (including viral hepatitis, active tuberculosis or positive tuberculosis screening).
    1. History of alcohol, drug, or chemical abuse, or a recent history of such abuse < 1 year prior to treatment.
    1. History of malignancies.
    1. Combined with severe mental disorders and other conditions and unable to cooperate with follow-up.

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Exposed group 1InebilizumabIntravenous methylprednisolone (IVMP) plus Inebilizumab
Exposed group 2Rituximab(RTX)IVMP plus Rituximab (RTX)
Primary Outcome Measures
NameTimeMethod
Change in Expanded Disability Status Scale Score (EDSS) from baseline.12 months

Change in Expanded Disability Status Scale (EDSS) score from baseline to 12 months after treatment (EDSS: Minimum Score 1, Maximum score 10, higher scores mean a worse outcome).

Time to first relapse12 months

Relapse: A monophasic clinical episode with patient-reported symptoms and objective findings reflecting a focal or multifocal inflammatory demyelinating event in the central nervous system (CNS), developing acutely or subacutely, with a duration of at least 24h, without fever or infection.

Number of new, and/or enlarging T2- hyperintense lesions detected by Magnetic Resonance Imaging (MRI)12 months

Number of new, and/or enlarging T2-hyperintense lesions detected by Magnetic Resonance Imaging (MRI) at the last visit.

Secondary Outcome Measures
NameTimeMethod
Change in Expanded Disability Status Scale (EDSS) score from baseline6 months

Change in Expanded Disability Status Scale (EDSS) score from baseline at month 6 (EDSS: Minimum Score 1, Maximum score 10, higher scores mean a worse outcome).

Change in modified Rankin score (mRS) from baseline12 months

Change in modified Rankin score (mRS) from baseline at month 12(mRS: Minimum Score 0, Maximum score 6, higher scores mean a worse outcome).

Change in serum glial fibrillary acidic protein antibody (GFAP-Ab) levels from baseline.12 months

Change in serum GFAP-Ab levels from baseline at the last visit

Change in serum Neurofilament light chain protein (NfL) levels from baseline.12 months

Change in serum NfL levels from baseline at the last visit.

Change in Visual Acuity (VA) from baseline12 months

Change in Visual Acuity (VA) at month 12.

Percentage of Participants with Disability Improvement12 months

Disability improvement is defined as a reduction in EDSS score of: A) \>=1.0 from the baseline EDSS score when the baseline score was \<=5.5 B) \>= 0.5 when the baseline EDSS score \> 5.5(EDSS: Minimum Score 1, Maximum score 10, higher scores mean a worse outcome).

Change in Timed 25 Foot Walk Test from baseline12 months

Change in time taken to complete the timed 25foot walk test from baseline

Adverse reactions during treatment and follow-up12 months
Percentage of Participants with Disability Worsening12 months

A participant was considered to have a worsening in overall EDSS score of at least 2 if baseline EDSS score was 0, or at least 1 point if baseline EDSS score is 1 to 5, or at least 0.5 point if baseline EDSS score is 5.5 or more.

Annual relapse rate (ARR) before and after Inebilizumab/Rituximab12 months

ARR will be measured in the baseline (according to patients' history before inebilizumab/rituximab) and after 12 months of intervention.

Change in aquaporin 4 antibody (AQP4-Ab) titers from baseline.12 months

Change in AQP4-ab titers from baseline at the last visit.

Changes in The Five Level of EuroQol Five Dimensions Questionnaire (EQ-5D-5L) scores from baseline12 months

Changes in EQ-5D scores from baseline at month 12(EQ-5D-5L: Minimum Score 5, Maximum score 25, lower scores mean a better quality of life).

Number of NMOSD attacked related rescue treatment.12 months
Change in retinal nerve fiber layer (RNFL) loss from baseline12 months

Change in retinal nerve fiber layer (RNFL) loss measured by optical coherence tomography (OCT) from baseline at month 12.

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