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

April 12, 2023 updated by: He Huang, Zhejiang University

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

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
9

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • China
    • Zhejiang
      • Hangzhou, Zhejiang, China, 310000
        • Recruiting
        • The first affiliated hospital of medical college of zhejiang university
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Maximum tolerable dose
Time Frame: From date of initial treatment to Day 28 post CD19 CAR-T infusion.
Maximum tolerable dose
From date of initial treatment to Day 28 post CD19 CAR-T infusion.
Dose-limiting toxicity (DLT)
Time Frame: Baseline up to 28 days after CD19 CAR T-cells infusion
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)
Time Frame: Up to 90 days after CD19 CAR T-cells infusion
Incidence of treatment-emergent adverse events [Safety and Tolerability]
Up to 90 days after CD19 CAR T-cells infusion

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Changes in serum AchR antibody titer
Time Frame: days 7, 14, 21, 28 and 90
Changes in serum AchR antibody titer
days 7, 14, 21, 28 and 90
MG-activities of daily living profile (MG-ADL)
Time Frame: Baseline up to 28 days after CD19 CAR T-cells infusion
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)
Time Frame: Baseline up to 28 days after CD19 CAR T-cells infusion
Quantitative Score for Myasthenia Gravis
Baseline up to 28 days after CD19 CAR T-cells infusion
Myasthenia Gravis Composite Scale (MGC)
Time Frame: Baseline up to 28 days after CD19 CAR T-cells infusion
Myasthenia Gravis Composite Scale
Baseline up to 28 days after CD19 CAR T-cells infusion
MG-QOL15 scale
Time Frame: Baseline up to 28 days after CD19 CAR T-cells infusion
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

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Zhejiang University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: He Huang, MD, Zhejiang University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 30, 2023

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 20, 2026

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 20, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 12, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 12, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 25, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 25, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 12, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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