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

Zhejiang University

Status and phase

Enrolling

Phase 1

Conditions

Myasthenia Gravis

Treatments

Drug: CD19 CAR-T cells injection

Study type

Interventional

Funder types

Other

Identifiers

NCT05828225

TXB2023006

Details and patient eligibility

About

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.

Enrollment

9 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

1. Age ≥18 and gender unlimited；
1. Confirmed as refractory myasthenia gravis with AchR antibody positive and accord one of the following three conditions
2. Repeated electrical stimulation suggests neuromuscular conduction deficits；
3. Tensilon test and neostigmine test positive;
4. The doctor judged that the symptoms of MG improved after treatment with oral cholinease inhibitors;
1. Consistent with the clinical classification of MGFA myasthenia gravis IIa-IVb (including IIa，IIb，IIIa， IIIb， IVa，IVb)
1. The baseline MG-ADL score ≥5 and the musculi oculi related score< 50 ；
1. Baseline QMG score>11;
1. 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；
1. The estimated survival time is more than 12 weeks;
1. 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;
1. 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 ;
1. Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythm ia in the past;
1. Pregnant (or lactating) women;
1. Patients with severe active infections;
1. Active infection of hepatitis B virus or hepatitis C virus;
1. Systemic steroids have used in the 4 weeks before participating in the treatment (except recently or currently using inhaled steroids);
1. Those who have used any gene therapy products before;
1. The proiferation rate is less than 5 times response to CD3/CD28 co-stimulation signal;
1. Serum creatinine > 2.5mg/dl or ALT / AST > 3 times ULN or bilirubin > 2.0 mg /dl;
1. Those who suffer from other uncontrolled diseases are not suitable to join the study;
1. HIV infection;
1. Any situation that the researchers believe may increase the risk of patients or interfere with the test results.