A Study of C-CAR168 in the Treatment of Central Nervous System Autoimmune Diseases Refractory to Standard Therapy

An Exploratory Clinical Study of Anti-CD20/B-cell Maturation Antigen(BCMA) Chimeric Antigen Receptor Autologous T Cell Product (C-CAR168) in the Treatment of Central Nervous System Autoimmune Diseases Refractory to Standard Therapy

This is an investigator-initiated, single-center, open-label study of C-CAR168, an autologous bi-specific CAR-T therapy targeting CD20 and BCMA, for the treatment of adult patients with central nervous system autoimmune diseases refractory to standard therapy

Study Overview

• Status: Not yet recruiting
• Conditions: Autoimmune Encephalitis; Multiple Sclerosis (MS); Stiff Person Syndrome; Neuromyelitis Optica Spectrum Disorders (NMOSD)
• Intervention / Treatment: Biological: CD20/BCMA-directed CAR-T cells

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Xiangjun Chen; Phone Number: +86 21 52888159; Email: xiangjchen@fudan.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 18 to 70 years old at the time of signing the Informed Consent Form (ICF).
• Diagnosed as Multiple Sclerosis (MS)/Neuromyelitis Optica Spectrum Disorders (NMOSD)/Autoimmune Encephalitis(AiE)/Stiff Person Spectrum Disorder(SPSD) according to recognized diagnostic criteria for at least 6 months.
• Prior treatment failure with standard therapy.
• Adequate bone marrow, coagulation, cardiopulmonary, liver and renal function.

Exclusion Criteria:

• Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), Human Immunodeficiency Virus (HIV), Treponema Pallidum (TP) positive, Cytomegalovirus (CMV) DNA positive, Epstein-Barr Virus (EBV) DNA positive.
• Uncontrolled active infection.
• Live vaccine injection within 4 weeks prior to signing the ICF.
• Major organ transplantation history or bone marrow/hematopoietic stem cell transplantation history.
• Severe cardiovascular diseases within the past 6 months prior to screening.
• A history of ≥ Grade 2 bleeding within 4 weeks prior to screening, or requiring long-term anticoagulants treatment.
• Inadequate washing time for previous treatment.
• Previously treated with CAR-T cell products or genetically modified T cell therapies.
• Pregnant or lactating women.
• Severe central nervous system diseases or pathological changes.
• Malignancy history within 5 years prior to signing the ICF.
• Any contraindication to lumbar puncture.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: C-CAR168; Autologous C-CAR168 administered by intravenous (IV) infusion	Biological: CD20/BCMA-directed CAR-T cells; Autologous 2nd generation CD20/BCMA-directed CAR-T cells, single infusion intravenously; Other Names: C-CAR168

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of Adverse Events [Safety and Tolerability]	Incidence and severity of adverse events (AE) and serious adverse events (SAE) within three months following infusion	Throughout the first 3 months follow up period completion
The subsequent recommended dose of C-CAR168 in patients with central nervous system autoimmune diseases refractory to standard therapy	Based on the assessment of overall safety profile	Throughout the first 24 months follow up period completion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of adverse events (AE)	Incidence and severity of adverse events (AE) and serious adverse events (SAE) during the study	Throughout the first 24 months follow up period completion
MS: No Evidence of Disease Activity-3 (NEDA-3)	Proportion of participants achieving NEDA-3 at 6 months post-infusion and during the study period	Throughout the first 24 months follow up period completion
MS and NMOSD: MRI	Number of T1 gadolinium-enhancing lesions and new or enlarging T2 lesions, as well as their change from baseline, at 6 months and 24 months post-infusion. Change from baseline in total T2 lesion volume, gray matter volume (GMV), white matter volume (WMV), and brain volume (BV), as well as annualized-brain volume loss (a-BVL), at 6 months and 24 months post-infusion	Throughout the first 24 months follow up period completion
MS, NMOSD and AiE: Annualized Relapse Rate (ARR)	ARR at 6 months and 24 months post-infusion	Throughout the first 24 months follow up period completion
Pharmacokinetics (PK): Maximal plasma concentration (Cmax)	Cmax of C-CAR168 in peripheral blood	Throughout the first 24 months follow up period completion
PK: Time to reach the maximal plasma concentration (Tmax)	Tmax of C-CAR168 in peripheral blood	Throughout the first 24 months follow up period completion
PK: Duration in peripheral blood (Tlast)	Tlast of C-CAR168 in peripheral blood	Throughout the first 24 months follow up period completion
PK: Area under curve (AUC)	AUC of C-CAR168 in peripheral blood	Throughout the first 24 months follow up period completion
Pharmacodynamics (PD): Depletion of peripheral blood B cells, plasma cells, and CD20dim T cells		Throughout the first 24 months follow up period completion
PD: Decline of serum immunoglobulin		Throughout the first 24 months follow up period completion
MS and NMOSD: Expanded Disability Status Scale (EDSS)	Change from baseline in EDSS at 6 months and 24 months post-infusion. 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 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).	Throughout the first 24 months follow up period completion
Autoimmune Encephalitis (AiE): Clinical Assessment Scale in Autoimmune Encephalitis (CASE)	Change from baseline in CASE at 6 months and 24 months post-infusion. The Clinical Assessment Scale in Autoimmune Encephalitis (CASE) has a score range from 0 to 27, and higher scores indicate a worse clinical outcome.	Throughout the first 24 months follow up period completion
Stiff-Person Syndrome (SPS): Distribution of Stiffness Index (DSI)	Change from baseline in DSI at 6 months and 24 months post-infusion. Distribution of Stiffness Index (DSI) is a validated indicator or stiffness. Scores range from 0 to 6 and reflect the extent of stiffness. Higher scores indicate a worse outcome.	Throughout the first 24 months follow up period completion
SPS: Heightened Sensitivity Score (HSS)	Change from baseline in HSS at 6 months and 24 months post-infusion. Heightened Sensitivity Score (HSS) measures changes in the frequency of spasms. Scores range from 0 to 7. Higher scores indicate a worse outcome.	Throughout the first 24 months follow up period completion

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum cytokines changes	Detection of serum cytokines changes over time by flow cytometry	Throughout the first 24 months follow up period completion
Soluble BCMA changes in peripheral blood	Detection of soluble BCMA changes in peripheral blood by Enzyme Linked ImmunoSorbent Assay (ELISA)	Throughout the first 24 months follow up period completion
Changes in CSF CAR DNA copy number and CAR-T cells	Detection of changes in CSF CAR DNA copy number and CAR-T cells by quantitative polymerase chain reaction (qPCR) and flow cytometry	Throughout the first 24 months follow up period completion

Collaborators and Investigators

• Sponsor: Huashan Hospital
• Collaborators: Shanghai AbelZeta Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): February 1, 2029

Study Registration Dates

• First Submitted: January 6, 2026
• First Submitted That Met QC Criteria: January 6, 2026
• First Posted (Estimated): January 14, 2026

Study Record Updates

• Last Update Posted (Actual): January 15, 2026
• Last Update Submitted That Met QC Criteria: January 13, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: CD20/BCMA-directed CAR-T cells
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases; Eye Diseases; Demyelinating Autoimmune Diseases, CNS; Demyelinating Diseases; Myelitis, Transverse; Optic Neuritis; Optic Nerve Diseases; Cranial Nerve Diseases; Spinal Cord Diseases; Multiple Sclerosis; Neuromyelitis Optica; Autoimmune Diseases of the Nervous System; Stiff-Person Syndrome
• Other Study ID Numbers: KY2025-1015

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