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

Neuromyelitis Optica Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05828212
• Other study ID #: TXB2023005
• Status: Recruiting
• Phase: Phase 1
• Start date: April 30, 2023
• Est. completion date: April 30, 2026

Study information

• Verified date: April 2023
• Source: Zhejiang University
• Contact: He Huang, MD
• Phone: +8613605714822
• Email: hehuangyu[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 9
• Est. completion date: April 30, 2026
• Est. primary completion date: April 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Neuromyelitis Optica

Intervention

Drug:
• CD19 CAR-T cells injection
CD19 CAR-T cells in the treatment of R/R neuromyelitis optica

Locations

Country	Name	City	State
China	The first affiliated hospital of medical college of zhejiang university	Hangzhou	Zhejiang

Sponsors (1)

Lead Sponsor	Collaborator
Zhejiang University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose limited toxicity (DLT)	Dose limited toxicity	From date of initial treatment to Day 28 post CD19 CAR-T infusion.
Primary	AE and SAE	Adverse event and serious adverse event	From admission to the end of the follow-up, up to 2 years
Primary	Maximum tolerable dose	Maximum tolerable dose	From date of initial treatment to Day 28 post CD19 CAR-T infusion.
Secondary	Changes in serum AQP4-IgG titer after infusion	Changes in serum AQP4-IgG titer after infusion	days 7, 14, 21, 28 and 90
Secondary	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
Secondary	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
Secondary	MRI active lesions	MRI active lesions	days 90
Secondary	Changes in optimal corrected vision	Changes in optimal corrected vision (Log MAR)	days 28 and 90
Secondary	Changes of nerve fiber layer around the retinal papilla(pRNFL)	Change in RNFL by optical coherence tomography over trial	2 years
Secondary	Changes in the plexiform layer of macular ganglion cells (mGCIPL)	Changes in the plexiform layer of macular ganglion cells (mGCIPL)	2 years
Secondary	Changes in Flash Visual Evoked Potential (FVEP)	Changes in Flash Visual Evoked Potential (FVEP)	2 years