Clinical trial NCT05828225: 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
Overall status: RECRUITING
Phase: PHASE1
Conditions: Myasthenia Gravis
Lead sponsor: Zhejiang University
Sponsor class: OTHER
First posted: 2023-04-25
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

  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.

Primary outcomes:
measure: Dose-limiting toxicity (DLT)
timeFrame: Baseline up to 28 days after CD19 CAR T-cells infusion
measure: Incidence of treatment-emergent adverse events (TEAEs)
timeFrame: Up to 90 days after CD19 CAR T-cells infusion
measure: Maximum tolerable dose
timeFrame: From date of initial treatment to Day 28 post CD19 CAR-T infusion.
Secondary outcomes:
measure: Changes in serum AchR antibody titer
timeFrame: days 7, 14, 21, 28 and 90
measure: MG-activities of daily living profile (MG-ADL)
timeFrame: Baseline up to 28 days after CD19 CAR T-cells infusion
measure: MG-activities of daily living profile (QMG)
timeFrame: Baseline up to 28 days after CD19 CAR T-cells infusion
measure: Myasthenia Gravis Composite Scale (MGC)
timeFrame: Baseline up to 28 days after CD19 CAR T-cells infusion
measure: MG-QOL15 scale
timeFrame: Baseline up to 28 days after CD19 CAR T-cells infusion
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: The first affiliated hospital of medical college of zhejiang university
state: Zhejiang
Study officials:
affiliation: Zhejiang University
name: He Huang, MD
role: PRINCIPAL_INVESTIGATOR
References: