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

Primary Purpose

Neuromyelitis Optica

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
CD19 CAR-T cells injection
Sponsored by
Zhejiang University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neuromyelitis Optica

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • The first affiliated hospital of medical college of zhejiang universityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment Group

Arm Description

Recurrent/Refractory Neuromyelitis Optica

Outcomes

Primary Outcome Measures

Dose limited toxicity (DLT)
Dose limited toxicity
AE and SAE
Adverse event and serious adverse event
Maximum tolerable dose
Maximum tolerable dose

Secondary Outcome Measures

Changes in serum AQP4-IgG titer after infusion
Changes in serum AQP4-IgG titer after infusion
Annual recurrence rate (ARR) of NMOSD
Annual recurrence rate (ARR) of NMOSD
Changes in the expanded disability status scale (EDSS) score from baseline
Changes in the expanded disability status scale (EDSS) score from baseline
MRI active lesions
MRI active lesions
Changes in optimal corrected vision
Changes in optimal corrected vision (Log MAR)
Changes of nerve fiber layer around the retinal papilla(pRNFL)
Change in RNFL by optical coherence tomography over trial
Changes in the plexiform layer of macular ganglion cells (mGCIPL)
Changes in the plexiform layer of macular ganglion cells (mGCIPL)
Changes in Flash Visual Evoked Potential (FVEP)
Changes in Flash Visual Evoked Potential (FVEP)

Full Information

First Posted
April 12, 2023
Last Updated
April 12, 2023
Sponsor
Zhejiang University
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1. Study Identification

Unique Protocol Identification Number
NCT05828212
Brief Title
Evaluate the Safety and Efficacy of CAR-T Cells in the Treatment of R/R Neuromyelitis Optica
Official Title
A Study on the Safety and Efficacy of Chimeric Antigen Receptor T Cells in the Treatment of Recurrent/Refractory Neuromyelitis Optica
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 30, 2023 (Anticipated)
Primary Completion Date
April 30, 2026 (Anticipated)
Study Completion Date
April 30, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Zhejiang University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neuromyelitis Optica

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
9 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment Group
Arm Type
Experimental
Arm Description
Recurrent/Refractory Neuromyelitis Optica
Intervention Type
Drug
Intervention Name(s)
CD19 CAR-T cells injection
Intervention Description
CD19 CAR-T cells in the treatment of R/R neuromyelitis optica
Primary Outcome Measure Information:
Title
Dose limited toxicity (DLT)
Description
Dose limited toxicity
Time Frame
From date of initial treatment to Day 28 post CD19 CAR-T infusion.
Title
AE and SAE
Description
Adverse event and serious adverse event
Time Frame
From admission to the end of the follow-up, up to 2 years
Title
Maximum tolerable dose
Description
Maximum tolerable dose
Time Frame
From date of initial treatment to Day 28 post CD19 CAR-T infusion.
Secondary Outcome Measure Information:
Title
Changes in serum AQP4-IgG titer after infusion
Description
Changes in serum AQP4-IgG titer after infusion
Time Frame
days 7, 14, 21, 28 and 90
Title
Annual recurrence rate (ARR) of NMOSD
Description
Annual recurrence rate (ARR) of NMOSD
Time Frame
From admission to the end of the follow-up, up to 2 years
Title
Changes in the expanded disability status scale (EDSS) score from baseline
Description
Changes in the expanded disability status scale (EDSS) score from baseline
Time Frame
days 7, 14, 21, 28 ,56 and 90
Title
MRI active lesions
Description
MRI active lesions
Time Frame
days 90
Title
Changes in optimal corrected vision
Description
Changes in optimal corrected vision (Log MAR)
Time Frame
days 28 and 90
Title
Changes of nerve fiber layer around the retinal papilla(pRNFL)
Description
Change in RNFL by optical coherence tomography over trial
Time Frame
2 years
Title
Changes in the plexiform layer of macular ganglion cells (mGCIPL)
Description
Changes in the plexiform layer of macular ganglion cells (mGCIPL)
Time Frame
2 years
Title
Changes in Flash Visual Evoked Potential (FVEP)
Description
Changes in Flash Visual Evoked Potential (FVEP)
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
He Huang, MD
Phone
+8613605714822
Email
hehuangyu@126.com
First Name & Middle Initial & Last Name or Official Title & Degree
Yongxian Hu, MD
Phone
+8615957162012
Email
huyongxian2000@aliyun.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
He Huang, MD
Organizational Affiliation
Zhejiang University
Official's Role
Principal Investigator
Facility Information:
Facility Name
The first affiliated hospital of medical college of zhejiang university
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
He Huang, MD
Phone
86-13605714822
Email
hehuangyu@126.com
First Name & Middle Initial & Last Name & Degree
Yongxian Hu, MD
Phone
+8615957162012
Email
huyongxian2000@aliyun.com

12. IPD Sharing Statement

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

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