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

Early Phase 1

Not yet recruiting

• Conditions: Myasthenia Gravis, Generalized; Chronic Inflammatory Demyelinating Polyradiculoneuropathy; Neuromyelitis Optica Spectrum Disorders; Multiple Sclerosis
• Interventions: Drug: Universal BCMA CAR-T; Universal CD19 CAR-T; Drug: Universal BCMA CAR-T; Drug: Universal CD19 CAR-T

• Registration Number: NCT06485232
• Lead Sponsor: Xuanwu Hospital, Beijing

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-06-20
• Study First Submitted QC: 2024-06-26
• Study First Posted: 2024-07-03
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-30
• Last Update Posted: 2025-01-01
• Study Start: 2025-02-28
• Primary Completion: 2026-12-31
• Study Completion: 2027-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 25

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
BCMA CAR-T + CD19 CAR-T Group	Universal BCMA CAR-T; Universal CD19 CAR-T	Universal BCMA CAR-T; Universal CD19 CAR-T
BCMA CAR-T Group	Universal BCMA CAR-T	Universal BCMA CAR-T
CD19 CAR-T Group	Universal CD19 CAR-T	Universal CD19 CAR-T

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
B cell levels in peripheral blood	3 months	The change of B cell levels in peripheral blood after infusion
MS: Changes of the number of Gd-enhancing T1 Lesions	6, 12months	The changes of enhancing Lesions as detected by brain Magnetic Resonance Imaging (MRI)
MS: Changes of the number of Number of New or Enlarging T2 Lesions	6, 12months	Number of new/enlarging T2 lesions on last available MRI scan compared to baseline.
Concentrations of UCAR-T cells	3 months	The concentration of BCMA UCAR T cells and CD19 UCAR-T cells in peripheral blood after infusion
Changes of pathogenic antibody titers after infusion	1, 3, 6 ,12months	The changes of pathogenic antibody titers in peripheral blood or cerebrospinal fluid.
NMOSD: Annualized relapse rate	6, 12months	ARR is defined as the number of relapses divided by the total participant-years after infusion
gMG: Changes of Myasthenia Gravis Activities if Daily Living (MG-ADL) Score	1, 3, 6, 12months	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.
CIDP:Changes of Inflammatory Neuropathy Cause and Treatment (INCAT) Score after infusion.	1, 3, 6, 12months	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.

Trial Locations

Locations (1)

Xuanwu Hospital, Capital Medical University; 🇨🇳 Beijing, Beijing, China