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Evaluate the Safety and Efficacy of CAR-T Cells in the Treatment of Refractory Myasthenia Gravis

Primary Purpose

Myasthenia Gravis

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 Myasthenia Gravis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 1. Age ≥18 and gender unlimited; 2. Confirmed as refractory myasthenia gravis with AchR antibody positive and accord one of the following three conditions Repeated electrical stimulation suggests neuromuscular conduction deficits; Tensilon test and neostigmine test positive; The doctor judged that the symptoms of MG improved after treatment with oral cholinease inhibitors; 3. Consistent with the clinical classification of MGFA myasthenia gravis IIa-IVb (including IIa,IIb,IIIa, IIIb, IVa,IVb) 4. The baseline MG-ADL score ≥5 and the musculi oculi related score< 50 ; 5. Baseline QMG score>11; 6. Regular treatment with poor efficacy and/or lack of effective treatment means that there is still recurrence or exacerbation after treatment with conventional hormones, immunosuppressants (such as azathioprine, mycophenolate mofetil, tacrolimus, cyclosporine A, cyclophosphamide, etc.) or rituximab; 7. The estimated survival time is more than 12 weeks; 8. 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. During the screening visit, the patient's thymectomy was less than 12 months or thymectomy was necessary during the study period or thymic radiation therapy ; 3. Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythm ia in the past; 4. Pregnant (or lactating) women; 5. Patients with severe active infections; 6. Active infection of hepatitis B virus or hepatitis C virus; 7. Systemic steroids have used in the 4 weeks before participating in the treatment (except recently or currently using inhaled steroids); 8. Those who have used any gene therapy products before; 9. The proiferation rate is less than 5 times response to CD3/CD28 co-stimulation signal; 10. Serum creatinine > 2.5mg/dl or ALT / AST > 3 times ULN or bilirubin > 2.0 mg /dl; 11. Those who suffer from other uncontrolled diseases are not suitable to join the study; 12. HIV infection; 13. 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

Myasthenia Gravis

Outcomes

Primary Outcome Measures

Dose-limiting toxicity (DLT)
Adverse events assessed according to NCI-CTCAE v5.0 criteria
Incidence of treatment-emergent adverse events (TEAEs)
Incidence of treatment-emergent adverse events [Safety and Tolerability]
Maximum tolerable dose
Maximum tolerable dose

Secondary Outcome Measures

Changes in serum AchR antibody titer
Changes in serum AchR antibody titer
MG-activities of daily living profile (MG-ADL)
MG-ADL Myasthenia Gravis Daily Activity Scale
MG-activities of daily living profile (QMG)
Quantitative Score for Myasthenia Gravis
Myasthenia Gravis Composite Scale (MGC)
Myasthenia Gravis Composite Scale
MG-QOL15 scale
MG-QOL15 Quality of Life Scale for Myasthenia Gravis (15 items)

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
NCT05828225
Brief Title
Evaluate the Safety and Efficacy of CAR-T Cells in the Treatment of Refractory Myasthenia Gravis
Official Title
A Study on the Safety and Efficacy of Chimeric Antigen Receptor T Cells in the Treatment of Refractory Myasthenia Gravis
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 20, 2026 (Anticipated)
Study Completion Date
April 20, 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 refractory myasthenia gravis, 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
Myasthenia Gravis

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
Myasthenia Gravis
Intervention Type
Drug
Intervention Name(s)
CD19 CAR-T cells injection
Intervention Description
CD19 CAR-T in the Treatment of Refractory Myasthenia Gravis
Primary Outcome Measure Information:
Title
Dose-limiting toxicity (DLT)
Description
Adverse events assessed according to NCI-CTCAE v5.0 criteria
Time Frame
Baseline up to 28 days after CD19 CAR T-cells infusion
Title
Incidence of treatment-emergent adverse events (TEAEs)
Description
Incidence of treatment-emergent adverse events [Safety and Tolerability]
Time Frame
Up to 90 days after CD19 CAR T-cells infusion
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 AchR antibody titer
Description
Changes in serum AchR antibody titer
Time Frame
days 7, 14, 21, 28 and 90
Title
MG-activities of daily living profile (MG-ADL)
Description
MG-ADL Myasthenia Gravis Daily Activity Scale
Time Frame
Baseline up to 28 days after CD19 CAR T-cells infusion
Title
MG-activities of daily living profile (QMG)
Description
Quantitative Score for Myasthenia Gravis
Time Frame
Baseline up to 28 days after CD19 CAR T-cells infusion
Title
Myasthenia Gravis Composite Scale (MGC)
Description
Myasthenia Gravis Composite Scale
Time Frame
Baseline up to 28 days after CD19 CAR T-cells infusion
Title
MG-QOL15 scale
Description
MG-QOL15 Quality of Life Scale for Myasthenia Gravis (15 items)
Time Frame
Baseline up to 28 days after CD19 CAR T-cells infusion

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 1. Age ≥18 and gender unlimited; 2. Confirmed as refractory myasthenia gravis with AchR antibody positive and accord one of the following three conditions Repeated electrical stimulation suggests neuromuscular conduction deficits; Tensilon test and neostigmine test positive; The doctor judged that the symptoms of MG improved after treatment with oral cholinease inhibitors; 3. Consistent with the clinical classification of MGFA myasthenia gravis IIa-IVb (including IIa,IIb,IIIa, IIIb, IVa,IVb) 4. The baseline MG-ADL score ≥5 and the musculi oculi related score< 50 ; 5. Baseline QMG score>11; 6. Regular treatment with poor efficacy and/or lack of effective treatment means that there is still recurrence or exacerbation after treatment with conventional hormones, immunosuppressants (such as azathioprine, mycophenolate mofetil, tacrolimus, cyclosporine A, cyclophosphamide, etc.) or rituximab; 7. The estimated survival time is more than 12 weeks; 8. 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. During the screening visit, the patient's thymectomy was less than 12 months or thymectomy was necessary during the study period or thymic radiation therapy ; 3. Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythm ia in the past; 4. Pregnant (or lactating) women; 5. Patients with severe active infections; 6. Active infection of hepatitis B virus or hepatitis C virus; 7. Systemic steroids have used in the 4 weeks before participating in the treatment (except recently or currently using inhaled steroids); 8. Those who have used any gene therapy products before; 9. The proiferation rate is less than 5 times response to CD3/CD28 co-stimulation signal; 10. Serum creatinine > 2.5mg/dl or ALT / AST > 3 times ULN or bilirubin > 2.0 mg /dl; 11. Those who suffer from other uncontrolled diseases are not suitable to join the study; 12. HIV infection; 13. 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
13605714822
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
0571-87233772
Email
hehuang@zju.edu.cn
First Name & Middle Initial & Last Name & Degree
Yongxian Hu, MD
Phone
+8615957162012
Email
huyongxian2000@aliyun.com

12. IPD Sharing Statement

Learn more about this trial

Evaluate the Safety and Efficacy of CAR-T Cells in the Treatment of Refractory Myasthenia Gravis

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