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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Myasthenia Gravis
• Intervention / Treatment: Drug: CD19 CAR-T cells injection

• Study Type: Interventional
• Enrollment (Anticipated): 9
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Yongxian Hu, MD; Phone Number: +8615957162012; Email: huyongxian2000@aliyun.com
• Study Contact Backup: Name: He Huang, MD; Phone Number: 13605714822; Email: hehuangyu@126.com

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • Recruiting
      • The first affiliated hospital of medical college of zhejiang university
      • Contact: Yongxian Hu, MD; Phone Number: +8615957162012; Email: huyongxian2000@aliyun.com
      • Contact: He Huang, MD; Phone Number: 0571-87233772; Email: hehuang@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Group; Myasthenia Gravis	Drug: CD19 CAR-T cells injection; CD19 CAR-T in the Treatment of Refractory Myasthenia Gravis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum tolerable dose	Maximum tolerable dose	From date of initial treatment to Day 28 post CD19 CAR-T infusion.
Dose-limiting toxicity (DLT)	Adverse events assessed according to NCI-CTCAE v5.0 criteria	Baseline up to 28 days after CD19 CAR T-cells infusion
Incidence of treatment-emergent adverse events (TEAEs)	Incidence of treatment-emergent adverse events [Safety and Tolerability]	Up to 90 days after CD19 CAR T-cells infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in serum AchR antibody titer	Changes in serum AchR antibody titer	days 7, 14, 21, 28 and 90
MG-activities of daily living profile (MG-ADL)	MG-ADL Myasthenia Gravis Daily Activity Scale	Baseline up to 28 days after CD19 CAR T-cells infusion
MG-activities of daily living profile (QMG)	Quantitative Score for Myasthenia Gravis	Baseline up to 28 days after CD19 CAR T-cells infusion
Myasthenia Gravis Composite Scale (MGC)	Myasthenia Gravis Composite Scale	Baseline up to 28 days after CD19 CAR T-cells infusion
MG-QOL15 scale	MG-QOL15 Quality of Life Scale for Myasthenia Gravis (15 items)	Baseline up to 28 days after CD19 CAR T-cells infusion

Collaborators and Investigators

• Sponsor: Zhejiang University
• Investigators: Principal Investigator: He Huang, MD, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Anticipated): April 30, 2023
• Primary Completion (Anticipated): April 20, 2026
• Study Completion (Anticipated): April 20, 2026

Study Registration Dates

• First Submitted: April 12, 2023
• First Submitted That Met QC Criteria: April 12, 2023
• First Posted (Actual): April 25, 2023

Study Record Updates

• Last Update Posted (Actual): April 25, 2023
• Last Update Submitted That Met QC Criteria: April 12, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Neoplasms; Autoimmune Diseases of the Nervous System; Autoimmune Diseases; Neoplasms by Site; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Neuromuscular Manifestations; Nervous System Neoplasms; Paraneoplastic Syndromes, Nervous System; Paraneoplastic Syndromes; Neuromuscular Junction Diseases; Muscle Weakness; Myasthenia Gravis
• Other Study ID Numbers: TXB2023006

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No