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

NCT05828225 | Recruiting Phase 1

• 1 other identifier: TXB2023006
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

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.

Conditions

Myasthenia Gravis

Outcome Measures

Primary Outcomes (3)

• 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

• Maximum tolerable dose

  Maximum tolerable dose

  From date of initial treatment to Day 28 post CD19 CAR-T infusion.

Secondary Outcomes (5)

• Changes in serum AchR antibody titer

  days 7, 14, 21, 28 and 90

• MG-activities of daily living profile (MG-ADL)

  Baseline up to 28 days after CD19 CAR T-cells infusion

• MG-activities of daily living profile (QMG)

  Baseline up to 28 days after CD19 CAR T-cells infusion

• Myasthenia Gravis Composite Scale (MGC)

  Baseline up to 28 days after CD19 CAR T-cells infusion

• MG-QOL15 scale

  Baseline up to 28 days after CD19 CAR T-cells infusion

Study Arms (1)

Treatment Group

EXPERIMENTAL

Myasthenia Gravis

Drug: CD19 CAR-T cells injection

Interventions

CD19 CAR-T cells injection DRUG

CD19 CAR-T in the Treatment of Refractory Myasthenia Gravis

Treatment Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Age ≥18 and gender unlimited；
• \. Confirmed as refractory myasthenia gravis with AchR antibody positive and accord one of the following three conditions
• Repeated electrical stimulation suggests neuromuscular conduction deficits；
• Tensilon test and neostigmine test positive;
• The doctor judged that the symptoms of MG improved after treatment with oral cholinease inhibitors;
• \. Consistent with the clinical classification of MGFA myasthenia gravis IIa-IVb (including IIa，IIb，IIIa， IIIb， IVa，IVb)
• \. The baseline MG-ADL score ≥5 and the musculi oculi related score\< 50 ；
• \. Baseline QMG score\>11;
• \. 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；
• \. The estimated survival time is more than 12 weeks;
• \. 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.

You may not qualify if:

• \. Epilepsy history or other central nervous system disease;
• \. 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 ;
• \. Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythm ia in the past;
• \. Pregnant (or lactating) women;
• \. Patients with severe active infections;
• \. Active infection of hepatitis B virus or hepatitis C virus;
• \. Systemic steroids have used in the 4 weeks before participating in the treatment (except recently or currently using inhaled steroids);
• \. Those who have used any gene therapy products before;
• \. The proiferation rate is less than 5 times response to CD3/CD28 co-stimulation signal;
• \. Serum creatinine \> 2.5mg/dl or ALT / AST \> 3 times ULN or bilirubin \> 2.0 mg /dl;
• \. Those who suffer from other uncontrolled diseases are not suitable to join the study;
• \. HIV infection;
• \. Any situation that the researchers believe may increase the risk of patients or interfere with the test results.

Sponsors & Collaborators

• Zhejiang University: lead

Study Sites (1)

The first affiliated hospital of medical college of zhejiang university

Hangzhou, Zhejiang, 310000, China

RECRUITING

MeSH Terms

Conditions

Myasthenia Gravis

Condition Hierarchy (Ancestors)

Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Paraneoplastic Syndromes; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Neurodegenerative Diseases; Neuromuscular Junction Diseases; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• He Huang, MD

  Zhejiang University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

He Huang, MD

CONTACT

13605714822; hehuangyu@126.com

Yongxian Hu, MD

CONTACT

+8615957162012; huyongxian2000@aliyun.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: April 12, 2023
• First Posted: April 25, 2023
• Study Start: April 30, 2023
• Primary Completion: April 20, 2026
• Study Completion: April 20, 2026
• Last Updated: April 25, 2023

Record last verified: 2023-04

Locations

CN (1)