Using CAR-T cells to treat difficult cases of Myasthenia Gravis

A Study on the Safety and Efficacy of Chimeric Antigen Receptor T Cells in the Treatment of Refractory Myasthenia Gravis

This study is testing a new CAR-T cell treatment for adults with tough cases of myasthenia gravis to see if it can help them feel better.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 9 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Zhejiang University (Academic / other)
• Drugs / interventions: rituximab, radiation, cyclophosphamide, CAR-T
• Locations: 1 site (Hangzhou, Zhejiang)
• Trial ID: NCT05828225 on ClinicalTrials.gov

What this trial studies

This is a single-arm, open-label, phase I clinical trial aimed at evaluating the safety and efficacy of CD19 CAR-T cell therapy in patients with refractory myasthenia gravis. The study will assess the pharmacokinetics of the CAR-T cells and monitor the participants for any adverse effects. Eligible patients must be adults with confirmed refractory myasthenia gravis and specific clinical criteria. The trial is conducted at a single center, focusing on a targeted patient population.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 and older with refractory myasthenia gravis who have tested positive for AchR antibodies.

Not a fit: Patients with myasthenia gravis that is not refractory or those who do not meet the specific inclusion criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with refractory myasthenia gravis who have not responded to conventional therapies.

How similar studies have performed: While CAR-T cell therapy has shown promise in other conditions, this specific application for refractory myasthenia gravis is novel and has not been extensively tested in prior studies.

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.

Where this trial is running

Hangzhou, Zhejiang

• The first affiliated hospital of medical college of zhejiang university — Hangzhou, Zhejiang, China (Recruiting)

Study contacts

• Principal investigator: He Huang, MD — Zhejiang University
• Study coordinator: He Huang, MD

Conditions Myasthenia Gravis