Myasthenia Gravis
Conditions
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.
Interventions
CD19 CAR-T in the Treatment of Refractory Myasthenia Gravis
Sponsors
Zhejiang University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 1. Repeated electrical stimulation suggests neuromuscular conduction deficits； 2. Tensilon test and neostigmine test positive; 3. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum tolerable dose | From date of initial treatment to Day 28 post CD19 CAR-T infusion. | Maximum tolerable dose |
| Dose-limiting toxicity (DLT) | Baseline up to 28 days after CD19 CAR T-cells infusion | Adverse events assessed according to NCI-CTCAE v5.0 criteria |
| Incidence of treatment-emergent adverse events (TEAEs) | Up to 90 days after CD19 CAR T-cells infusion | Incidence of treatment-emergent adverse events \[Safety and Tolerability\] |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Myasthenia Gravis Composite Scale (MGC) | Baseline up to 28 days after CD19 CAR T-cells infusion | Myasthenia Gravis Composite Scale |
| Changes in serum AchR antibody titer | days 7, 14, 21, 28 and 90 | Changes in serum AchR antibody titer |
| MG-QOL15 scale | Baseline up to 28 days after CD19 CAR T-cells infusion | MG-QOL15 Quality of Life Scale for Myasthenia Gravis (15 items) |
| MG-activities of daily living profile (MG-ADL) | Baseline up to 28 days after CD19 CAR T-cells infusion | MG-ADL Myasthenia Gravis Daily Activity Scale |
| MG-activities of daily living profile (QMG) | Baseline up to 28 days after CD19 CAR T-cells infusion | Quantitative Score for Myasthenia Gravis |
Countries
China
Contacts
Primary ContactHe Huang, MD
Backup ContactYongxian Hu, MD
Outcome results
None listed