Evaluate the Safety and Efficacy of CAR-T Cells in the Treatment of R/R Neuromyelitis Optica

Study Overview
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Brief Summary
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This is a single-arm, open-label, single-center, phase I study. The primary objective is to evaluate the safety of CD19 CAR-T therapy for patients with relapsed or refractory Neuromyelitis Optica, and to evaluate the pharmacokinetics of CD19 CAR-T in patients.

Official Title
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A Study on the Safety and Efficacy of Chimeric Antigen Receptor T Cells in the Treatment of Recurrent/Refractory Neuromyelitis Optica

Conditions
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Neuromyelitis Optica

Intervention / Treatment
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* Drug: CD19 CAR-T cells injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Age 18-60 and gender unlimited; 2. NMOSD diagnosed based on the 2015 NMOSD International Consensus Diagnostic Criteria; 3. Diagnostic criteria for AQP4-IgG positive NMOSD Diagnostic criteria for AQP4-IgG positive NMOSD At least 1 core clinical feature Using reliable methods to detect positive AQP4-IgG (CBA method) Exclude other diagnoses. Core clinical features ＯＮ Acute myelitis Posterior region syndrome, unexplained paroxysmal hiccup, nausea, and vomiting Other brainstem syndromes Symptomatic episodic sleeping sickness, diencephalic syndrome, brain MRI with NMOSD characteristic diencephalic lesions Cerebral syndrome with NMOSD characteristic brain lesions 4. Corticosteroids combined with immunosuppressants (azathioprine or mycophenolate mofetil or rituximab) still relapse after treatment； 5. At least 2 relapses within the past 12 months or at least 3 relapses within the past 24 months, and at least 1 recurrence within the 12 months prior to screening； 6. The estimated survival time is more than 12 weeks; 7. Women of childbearing age who have negative urine pregnancy test before medication administration and agree to take effective contraceptive measures during the trial period until the last follow-up Exclusion Criteria: 1. Epilepsy history or other central nervous system disease; 2. Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythm ia in the past; 3. Pregnant (or lactating) women; 4. Patients with severe active infections; 5. Active infection of hepatitis B virus or hepatitis C virus; 6. Systemic steroids have used in the 4 weeks before participating in the treatment (except recently or currently using inhaled steroids); 7. Those who have used any gene therapy products before; 8. The proiferation rate is less than 5 times response to CD3/CD28 co-stimulation signal; 9. Serum creatinine > 2.5mg/dl or ALT / AST > 3 times ULN or bilirubin > 2.0mg/dl; 10. Those who suffer from other uncontrolled diseases are not suitable to join the study; 11. HIV infection; 12. Any situation that the researchers believe may increase the risk of patients or interfere with the test results.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Group<br>Recurrent/Refractory Neuromyelitis Optica | Drug: CD19 CAR-T cells injection<br>* CD19 CAR-T cells in the treatment of R/R neuromyelitis optica<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose limited toxicity (DLT) | Dose limited toxicity | From date of initial treatment to Day 28 post CD19 CAR-T infusion. | 
| AE and SAE | Adverse event and serious adverse event | From admission to the end of the follow-up, up to 2 years | 
| Maximum tolerable dose | Maximum tolerable dose | From date of initial treatment to Day 28 post CD19 CAR-T infusion. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in serum AQP4-IgG titer after infusion | Changes in serum AQP4-IgG titer after infusion | days 7, 14, 21, 28 and 90 | 
| Annual recurrence rate (ARR) of NMOSD | Annual recurrence rate (ARR) of NMOSD | From admission to the end of the follow-up, up to 2 years | 
| Changes in the expanded disability status scale (EDSS) score from baseline | Changes in the expanded disability status scale (EDSS) score from baseline | days 7, 14, 21, 28 ,56 and 90 | 
| MRI active lesions | MRI active lesions | days 90 | 
| Changes in optimal corrected vision | Changes in optimal corrected vision (Log MAR) | days 28 and 90 | 
| Changes of nerve fiber layer around the retinal papilla(pRNFL) | Change in RNFL by optical coherence tomography over trial | 2 years | 
| Changes in the plexiform layer of macular ganglion cells (mGCIPL) | Changes in the plexiform layer of macular ganglion cells (mGCIPL) | 2 years | 
| Changes in Flash Visual Evoked Potential (FVEP) | Changes in Flash Visual Evoked Potential (FVEP) | 2 years |