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

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

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.

Study Overview

• Status: Completed
• Conditions: Neuromyelitis Optica
• Intervention / Treatment: Drug: CAR-T cells injection

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • The first affiliated hospital of medical college of zhejiang university

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

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

  1. At least 1 core clinical feature
  2. Using reliable methods to detect positive AQP4-IgG (CBA method)
  3. Exclude other diagnoses. Core clinical features
  1. ＯＮ
  2. Acute myelitis
  3. Posterior region syndrome, unexplained paroxysmal hiccup, nausea, and vomiting
  4. Other brainstem syndromes
  5. Symptomatic episodic sleeping sickness, diencephalic syndrome, brain MRI with NMOSD characteristic diencephalic lesions
  6. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Group; Recurrent/Refractory Neuromyelitis Optica	Drug: CAR-T cells injection; CAR-T cells in the treatment of R/R neuromyelitis optica

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AE and SAE	Adverse event and serious adverse event	From admission to the end of the follow-up, up to 2 years
Dose limited toxicity (DLT)	Dose limited toxicity	From date of initial treatment to Day 28 post CAR-T infusion.
Maximum tolerable dose	Maximum tolerable dose	From date of initial treatment to Day 28 post 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 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 expanded disability status scale (EDSS) score from baseline	EDSS:0 (normal neurological exam) to 10 (death due to MS),Higher scores indicate greater disability (worse outcome)，Score reduction suggests functional improvement	days 7, 14, 21, 28 ,56 and 90
MRI active lesions	Proportion of subjects with ≥1 active lesions at Day 90	days 90
Changes in the plexiform layer of macular ganglion cells (mGCIPL)	Proportion of subjects with significant mGCIPL thickness changes	2 years

Collaborators and Investigators

• Sponsor: Zhejiang University
• Collaborators: Yake Biotechnology Ltd.
• Investigators: Principal Investigator: He Huang, MD, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2023
• Primary Completion (Actual): July 30, 2025
• Study Completion (Actual): July 30, 2025

Study Registration Dates

• First Submitted: April 12, 2023
• First Submitted That Met QC Criteria: April 12, 2023
• First Posted (Actual): April 25, 2023

Study Record Updates

• Last Update Posted (Actual): August 11, 2025
• Last Update Submitted That Met QC Criteria: August 5, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Autoimmune Diseases; Immune System Diseases; Eye Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Myelitis, Transverse; Optic Neuritis; Optic Nerve Diseases; Cranial Nerve Diseases; Neuromyelitis Optica
• Other Study ID Numbers: TXB2023005

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No