Universal CAR-T Cells in Patients with Refractory Autoimmune Diseases of the Nervous System.

An Exploratory Study on the Safety and Efficacy of Universal CAR-T Cells Targeting BCMA and CD19 in the Treatment of Refractory Autoimmune Diseases of the Nervous System

This is an open label, single-site, dose-escalation study in up to 25 participants with refractory autoimmune diseases of nervous system. This study aims to evaluate the safety and efficacy of the treatment with universal BCMA and CD19 CART.

Study Overview

• Status: Not yet recruiting
• Conditions: Multiple Sclerosis; Neuromyelitis Optica Spectrum Disorders; Chronic Inflammatory Demyelinating Polyradiculoneuropathy; Myasthenia Gravis, Generalized
• Intervention / Treatment: Drug: Universal BCMA CAR-T; Drug: Universal CD19 CAR-T; Drug: Universal BCMA CAR-T; Universal CD19 CAR-T

• Study Type: Interventional
• Enrollment (Estimated): 25
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Junwei Hao, MD;PhD; Phone Number: 01083198277; Email: haojunwei@vip.163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100053
      • Xuanwu Hospital, Capital Medical University
      • Contact: Junwei Hao, MD; PhD; Phone Number: 01083198277; Email: haojunwei@vip.163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Aged 18-75 years (for MS patients, 18-55 years); both genders eligible.
• Subjects with refractory neurological autoimmune diseases who have failed standard treatment or lack effective treatment, Including neuromyelitis optica spectrum disorders(NMOSD), generalized myasthenia gravis(gMG), chronic inflammatory demyelinating Polyradiculoneuropathy(CIDP) and multiple sclerosis(MS).
• Anticipated survival of ≥ 12 weeks as judged by the researcher.
• Agrees to use double barrier methods, condoms, oral or injectable contraceptives, or intrauterine devices during the study period and for one year after taking the study medication.
• Provides written informed consent.

Exclusion Criteria:

• History of solid organ transplantation.
• Malignant tumor within the last two years.
• Positive for Hepatitis B surface antigen (HBsAg) or Hepatitis B core antibody (HBcAb), with peripheral blood Hepatitis B virus (HBV) DNA detected as positive; positive for Hepatitis C virus antibodies, with peripheral blood Hepatitis C virus RNA detected as positive; positive for Human Immunodeficiency Virus (HIV) antibodies; positive for Cytomegalovirus (CMV) DNA; positive for syphilis.
• Primary immunodeficiency (congenital or acquired).
• Severe cardiac disease.
• History of psychiatric disorders or history of psychotropic drug abuse, with no history of withdrawal.
• Allergic constitution or a history of severe allergies.
• Pregnant or breastfeeding women.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BCMA CAR-T Group; Universal BCMA CAR-T	Drug: Universal BCMA CAR-T; Universal BCMA CAR-T
Experimental: CD19 CAR-T Group; Universal CD19 CAR-T	Drug: Universal CD19 CAR-T; Universal CD19 CAR-T
Experimental: BCMA CAR-T + CD19 CAR-T Group; Universal BCMA CAR-T; Universal CD19 CAR-T	Drug: Universal BCMA CAR-T; Universal CD19 CAR-T; Universal BCMA CAR-T; Universal CD19 CAR-T

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of dose-limiting toxicities(DLTs)	Incidence of dose-limiting toxicities(DLTs)	First 28 days after infusion
Incidence of adverse events(AEs) and severe adverse	Incidence of adverse events(AEs) and severe adverse events(SAEs).	Up to 12 months after infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentrations of UCAR-T cells	The concentration of BCMA UCAR T cells and CD19 UCAR-T cells in peripheral blood after infusion	3 months
B cell levels in peripheral blood	The change of B cell levels in peripheral blood after infusion	3 months
Changes of pathogenic antibody titers after infusion	The changes of pathogenic antibody titers in peripheral blood or cerebrospinal fluid.	1, 3, 6 ,12months
NMOSD: Annualized relapse rate	ARR is defined as the number of relapses divided by the total participant-years after infusion	6, 12months
gMG: 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 gMG. 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 gMG.	1, 3, 6, 12months
CIDP:Changes of Inflammatory Neuropathy Cause and Treatment (INCAT) Score after infusion.	The INCAT score assesses the functionality of the arms and legs by giving a 0-5 score for arms and legs, with 0 representing no disability and 5 representing no arm function or inability to stand/walk.	1, 3, 6, 12months
MS: Changes of the number of Gd-enhancing T1 Lesions	The changes of enhancing Lesions as detected by brain Magnetic Resonance Imaging (MRI)	6, 12months
MS: Changes of the number of Number of New or Enlarging T2 Lesions	Number of new/enlarging T2 lesions on last available MRI scan compared to baseline.	6, 12months

Collaborators and Investigators

• Sponsor: Xuanwu Hospital, Beijing
• Collaborators: Bioray Laboratories

Study record dates

Study Major Dates

• Study Start (Estimated): February 28, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: June 20, 2024
• First Submitted That Met QC Criteria: June 26, 2024
• First Posted (Actual): July 3, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 30, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Multiple Sclerosis; Myasthenia Gravis; Neuromyelitis Optica Spectrum Disorders; universal CAR-T; Chronic Inflammatory Demyelinating Polyradiculoneuropathy
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Neuromuscular Diseases; Chronic Disease; Disease Attributes; 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; Multiple Sclerosis; Sclerosis; Myasthenia Gravis; Neuromyelitis Optica; Autoimmune Diseases; Nervous System Diseases; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Polyradiculoneuropathy; Autoimmune Diseases of the Nervous System
• Other Study ID Numbers: 2024-BRL-302-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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