UCAR T-cell Therapy Targeting CD19/BCMA in Patients With r/r Myasthenia Gravis

NCT06933563 | Not Yet Recruiting Early Phase 1

• 1 other identifier: QH-ZY-03
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open label, single-site, dose-escalation study in up to 18 participants with relapsed or refractory Myasthenia gravis. This study aims to evaluate the safety and efficacy of the treatment with universal CD19/BCMA CAR T-cells.

Conditions

Myasthenia Gravis

Keywords

Universal Allogeneic CAR T-cells; CD19/BCMA CAR T-cells

Outcome Measures

Primary Outcomes (4)

• The number and severity of dose-limiting toxicity (DLT) events

  DLT will be graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0, and the ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells.

  Within 28 Days After UCAR T-cell Infusion

• The total number, incidence, and severity of AEs

  Up to 90 days After UCAR T-cell Infusion

• Changes of Myasthenia Gravis Activities if Daily Living (MG-ADL) Score

  MG-ADL scale assesses the impact of gMG on daily functions by measuring 8 signs or symptoms that are commonly affected in MG. Each item is measured on a 4-point scale, where a score of 0 represents normal function and a score of 3 represents the loss of ability to perform that function. Total scores range from 0 to 24 points, with a higher score showing more severe MG.

  Up to 24 Months After UCAR T-cell Infusion

• Quantitative Myasthenia Gravis Score (QMG)

  The QMG score is a 13-item scale used to quantify disease severity in myasthenia gravis. The scale measures ocular, bulbar, respiratory, and limb function, grading each finding, and ranges from 0 (no myasthenic findings) to 39 (maximal myasthenic deficits).

  Up to 24 Months After UCAR T-cell Infusion

Study Arms (1)

anti-CD19/BCMA CAR T-cells

EXPERIMENTAL

Universal allogeneic CD19/BCMA CAR T-cells

Biological: UCAR T-cell group

Interventions

UCAR T-cell group BIOLOGICAL

A single injection of UCAR T-cells, referred to as universal allogeneic anti-CD19/BCMA CAR T-cells

anti-CD19/BCMA CAR T-cells

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years
• Flow cytometry detected positive B cell CD19 or BCMA in the patient's peripheral blood.
• Patients with relapsed refractory myasthenia gravis (MG) who have positive abnormal antibodies, the total score of MG-ADL ≥5, and the eye muscle score \< 50% of the total score; It is classified as Grade II-IV according to the 2020 MGFA diagnostic criteria.
• Specific requirements include: i. Receiving standardized treatment with at least one immunosuppressant for more than 1 year, and having any of the following malcontrolled conditions: 1) persistent inability to affect daily life; 2) Aggravation of MG symptoms and/or crisis episodes occur despite standard treatment; 3) Inability to tolerate immunosuppressive therapy. ii. plasma exchange or maintenance of intravenous immunoglobulin therapy is required.
• Functional requirements for major organs are as follows:
• The bone marrow function needs to meet: a Neutrophil count ≥ 1.5× 10 \^ 9/L; b. Hemoglobin ≥90g/L: c. Platelets ≥ 80 × 10 \^ 9/L.
• Liver function: ALT ≤ 3 × UL; AST ≤ 3×ULN# Total bilirubin ≤ 2.0 ×ULN (excluding Gilbert syndrome, total bilirubin ≤ 3.0 × ULN).
• Renal function: creatinine clearance rate (CrCl) ≥ 30 ml/min(Cockcroft/Gault formula, excluding acute CrCl decline caused by the disease itself).
• Female subjects of childbearing potential and male subjects with partners of childbearing potential must use medically approved contraception or abstinence during the study treatment period and for at least 6 months after the end of the study treatment; Female subjects of childbearing potential must have a negative Human chorionic gonadotropin (HCG) test within 7 days before study enrollment and not be lactating.
• Willing to participate in this clinical study, sign an informed consent form, have good compliance, and cooperate with follow-up.

You may not qualify if:

• Subjects with a history of severe drug allergies or allergic tendencies.
• Presence or suspicion of uncontrolled or treatment-required fungal,bacterial, viral, or other infections.
• Subjects with central nervous system diseases caused by autoimmune diseases or non-autoimmune diseases (including epilepsy, psychosis, organic brain syndrome, cerebral vascular accidents, encephalitis, central nervous system vasculitis).
• Subjects with insufficient cardiac function.
• Subjects with congenital immunoglobulin deficiencies.
• History of malignancy within five years.
• Subjects with end-stage renal failure.
• Subjects who are positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with peripheral blood HBV DNA titer higher than the upper limit of detection; subjects positive for hepatitis C virus (HCV) antibody and peripheral blood HCV RNA; individuals positive for human immunodeficiency virus (HIV) antibody; individuals positive for syphilis testing.
• Subjects with psychiatric disorders and severe cognitive impairments.
• Subjects who had participated in other clinical trials within 3 months prior to enrollment.
• Subjects who have used immunosuppressive agents or biologics with therapeutic effects on the disease within five half-life before enrollment
• Pregnant women or women planning to conceive

Sponsors & Collaborators

• Zhejiang University: lead
• Shanghai Xiniao Biotech Co., Ltd.: collaborator

Study Sites (1)

The first affiliated hospital of medical college of zhejiang university

Hangzhou, Zhejiang, China

Location

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

Central Study Contacts

He Huang

CONTACT

86-13605714822; hehuangyu@126.com

Yongxian Hu

CONTACT

86-15957162012; Huyongxian2000@aliyun.com

Study Design

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

Study Record Dates

• First Submitted: April 2, 2025
• First Posted: April 18, 2025
• Study Start: April 1, 2025
• Primary Completion: April 1, 2026
• Study Completion (Estimated): November 1, 2027
• Last Updated: April 18, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)