Universal Chimeric Antigen Receptor T-Cell （UCAR T-cell） Therapy Targeting CD19/B Cell Maturation Antigen （CD19/BCMA） in Patients With r/r Neurological Autoimmune Diseases

A Clinical Study Evaluating the Safety and Preliminary Efficacy of Universal Allogeneic CAR T-cell Therapy Targeting CD19 and BCMA in Patients With Relapsed / Refractory Neurological Autoimmune Diseases

This is an open label, single-site, dose-escalation study in up to 12 participants with relapsed or refractory Neurological Autoimmune Diseases. This study aims to evaluate the safety and efficacy of the treatment with universal CD19/BCMA CAR T-cells.

Study Overview

• Status: Recruiting
• Conditions: Multiple Sclerosis; Myasthenia Gravis; Autoimmune Encephalitis; Neuromyelitis Optica Spectrum Disorders; Chronic Inflammatory Demyelinating Polyradiculoneuropathy
• Intervention / Treatment: Drug: UCAR T-cell

Detailed Description

This is an investigator-initiated trial to evaluate the safety and efficacy of universal CD19/BCMA CAR T-cells in Relapsed or Refractory Neurological Autoimmune Diseases.

Study intervention consists of a single infusion of universal CAR T-cells administered intravenously after a lymphodepleting therapy regimen consisting of fludarabine and cyclophosphamide.

Interim analysis will be performed when participants finish the visit 90 days after CAR T-cell infusion.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Jialing Wu; Phone Number: 86-18622271026; Email: wywjl2009@hotmail.com
• Study Contact Backup: Name: Guanen Zhou; Phone Number: 86-13920273016; Email: tjzge@163.com

Study Locations

• China
  • Tianjin, China
    • Recruiting
    • Tianjin Huanhu Hospital
    • Contact: Jialing Wu; Phone Number: 86-18622271026; Email: wywjl2009@hotmail.com
    • Contact: Email: tjzge@163.com
    • Principal Investigator: Jialing Wu
    • Principal Investigator: Guanen Zhou

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age ≥ 18 years.
• Flow cytometry detected positive B cell CD19 or BCMA in the patient's peripheral blood.
• Subjects with relapsed or refractory neurological autoimmune diseases, Including neuromyelitis optica spectrum disorders(NMOSD), myasthenia gravis(MG), multiple sclerosis(MS)，Autoimmune encephalitis(AE) and chronic inflammatory demyelinating Polyradiculoneuropathy(CIDP).
• 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.

Exclusion Criteria:

• Subjects with a history of severe drug allergies or allergic tendencies.
• History of malignancy within five years.
• Subjects with insufficient cardiac function.
• Subjects who are positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with peripheral blood HBV DNA >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.
• Pregnant women or women planning to conceive.

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: UCAR T-cell group; Universal allogeneic CD19/BCMA CAR T-cells	Drug: UCAR T-cell; Universal allogeneic anti-CD19/BCMA CAR T-cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NMOSD、MS: Expanded Disability Status Scale (EDSS) score	EDSS and its associated functional system (FS) score provide a system for quantifying disability and monitoring changes in the level of disability over time. EDSS is a scale for assessing neurologic impairment in multiple sclerosis (MS). It consists of 7 FS (visual FS, brainstem FS, pyramidal FS, cerebellar FS, sensory FS, bowel and bladder FS, and cerebral FS) which are used to derive EDSS score ranging from 0 (normal neurological exam) to 10 (death from MS). A negative change from baseline indicates improvement. A participant was considered to have a worsening in overall EDSS score of at least 2 if baseline EDSS score was 0, or at least 1 point if baseline EDSS score is 1 to 5, or at least 0.5 point if baseline EDSS score is 5.5 or more.	Up to 24 Months After UCAR T-cell Infusion
NMOSD、MS: Modified Rankin Scale	Modified Rankin Scale (mRS) is a profoundly valid and reliable measure of disability and is broadly utilized for assessing stroke outcomes and degree of disability. We characterized a favorable outcome as mRS ranging from zero up to two, while unfavorable outcome ranging for 3 up to 6.	Up to 24 Months After UCAR T-cell Infusion
MG: 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
MG: Myasthenia Gravis Activities if Daily Living (MG-ADL) Score	The MG-ADL is an eight-question survey of symptom severity, with each response graded from 0 (normal) to 3 (most severe). Two questions concern ocular, three oropharyngeal, one respiratory, and two extremity functions. Cumulative MG-ADL scores range from 0 to 24	Up to 24 Months After UCAR T-cell Infusion
CIDP: Inflammatory Neuropathy Cause and Treatment (INCAT) Score	The INCAT score comprises two parts, the arm score and the leg score. Based on a patient's level of impairment in their arms and legs, each part is scored between 0 and 5 points, resulting in an INCAT total score between 0 and 10.	Up to 24 Months After UCAR T-cell Infusion
AE: Change in CASE	The changes of Clinical Assessment Scale in Autoimmune Encephalitis (CASE) score from baseline.	Up to 24 Months After UCAR T-cell Infusion

Collaborators and Investigators

• Sponsor: Tianjin Huanhu Hospital
• Collaborators: Shanghai Xiniao Biotech Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): June 17, 2025
• Primary Completion (Estimated): April 1, 2026
• Study Completion (Estimated): October 1, 2027

Study Registration Dates

• First Submitted: April 6, 2025
• First Submitted That Met QC Criteria: April 14, 2025
• First Posted (Actual): April 22, 2025

Study Record Updates

• Last Update Posted (Actual): December 15, 2025
• Last Update Submitted That Met QC Criteria: December 11, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Universal Allogeneic CAR T-cells
• Additional Relevant MeSH Terms: Nervous System Diseases; Pathologic Processes; Neoplasms by Site; Neoplasms; Neuromuscular Diseases; Chronic Disease; Disease Attributes; Autoimmune Diseases; Immune System Diseases; Peripheral Nervous System Diseases; Eye Diseases; Demyelinating Autoimmune Diseases, CNS; Demyelinating Diseases; Neurodegenerative Diseases; Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Paraneoplastic Syndromes; Neuromuscular Junction Diseases; Myelitis, Transverse; Optic Neuritis; Optic Nerve Diseases; Cranial Nerve Diseases; Polyneuropathies; Polyradiculoneuropathy; Pathological Conditions, Signs and Symptoms; Multiple Sclerosis; Myasthenia Gravis; Neuromyelitis Optica; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Autoimmune Diseases of the Nervous System
• Other Study ID Numbers: QH-HH-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No