A Study of C-CAR168 in the Treatment of 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 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 autoimmune diseases refractory to standard therapy

Study Overview

• Status: Not yet recruiting
• Conditions: Systemic Lupus Erythematosus; Systemic Sclerosis; Neuromyelitis Optica Spectrum Disorder; Multiple Sclerosis (MS); Immune-Mediated Necrotizing Myopathy; Myasthenia Gravis (MG)
• Intervention / Treatment: Biological: CD20/BCMA-directed CAR-T cells Autologous 2nd generation

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Min Liu, MD; Phone Number: 17853297267; Email: liumin1968@yeah.net
• Study Contact Backup: Name: Bin Liu, MD; Phone Number: 053282919030 18661806287; Email: Binliu72314@163.com

Study Locations

• China
  • Qindao, Shandong
    • Qingdao, Qindao, Shandong, China, 266003
      • The Affiliated Hospital of Qingdao University
      • Contact: Min Liu, MD; Phone Number: 17853297267; Email: liumin1968@yeah.net
      • Contact: Bin Liu, MD; Phone Number: 053282919030 18661806287; Email: Binliu72314@163.com

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)/Myasthenia Gravis (MG)/Systemic Lupus Erythematosus (SLE)/ Systemic Sclerosis (SSc)/ Immune-Mediated Necrotizing Myopathy (IMNM) 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 for MS or NMOSD.

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 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
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
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
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 and NMOSD: Annualized Relapse Rate (ARR)	ARR at 6 months and 24 months post-infusion	Throughout the first 24 months follow up period completion
MG: Minimal Symptom Expression (MSE) and Minimal Clinically Important Difference (MCID)	Proportion of participants achieving MSE or MCID at 6 months and 24 months post-infusion	Throughout the first 24 months follow up period completion
MG: Quantitative Myasthenia Gravis Score (QMGS)	Change from baseline in QMGS at 6 months and 24 months post-infusion. The Quantitative Myasthenia Gravis Score (QMGS) has a score range from 0 to 39, and higher scores indicate a worse clinical outcome.	Throughout the first 24 months follow up period completion
MG: Myasthenia Gravis Activities of Daily Living (MG-ADL) Scale	Change from baseline in MG-ADL at 6 months and 24 months post-infusion. The Myasthenia Gravis Activities of Daily Living (MG-ADL) Scale has a score range from 0 to 24, and higher scores indicate a worse clinical outcome.	Throughout the first 24 months follow up period completion
SLE: Definition Of Remission In SLE (DORIS), Lupus Low Disease Activity State (LLDAS), Systemic Lupus Erythematosus Responder Index-4 (SRI-4)	Proportion of participants achieving DORIS or LLDAS or SRI-4 at 6 months post-infusion and during the study period	Throughout the first 24 months follow up period completion
SLE: Systemic Lupus Erythematosus Disease Activity Index 2000(SLEDAI-2K),	Change from baseline in SLEDAI-2K at 6 months and 24 months post-infusion. SLEDAI-2K is a validated global disease-activity index that quantifies SLE activity by rating the presence of 24 weighted clinical and laboratory descriptors across 9 organ systems (central nervous/visual, vascular, renal, musculoskeletal, cutaneous, mucosal/serosal, constitutional, and immunologic/hematologic) occurring within the prior 10 days. Each descriptor is credited only if attributable to active lupus (not infection, drug effect, metabolic cause, or unrelated comorbidity); descriptors are summed for a total score range 0-105, with higher scores indicating greater disease activity.	Throughout the first 24 months follow up period completion
IMNM: Definition Of Improvement (DOI)	Proportion of participants achieving DOI at 6 months post-infusion and during the study period	Throughout the first 24 months follow up period completion
IMNM: Manual Muscle Test (MMT)	Change from baseline in MMT at 6 months and 24 months post-infusion. MMT scale is a foundational, internationally recognized clinical tool for quantifying voluntary skeletal muscle strength in patients with neurologic and systemic diseases.	Throughout the first 24 months follow up period completion
SSc: Revised Composite Response Index in Systemic Sclerosis (r-CRISS)	Proportion of participants achieving r-CRISS at 6 months post-infusion and during the	Throughout the first 24 months follow up period completion
SSc: modified Rodnan Skin Score (mRSS), FVC%	Change from baseline in mRSS and FVC% at 6 months and 24 months post-infusion. mRSS is the international standard semi quantitative measure of skin thickening in SSc. Scores are summed for a total range of 0-51, with higher scores indicating greater skin involvement.	Throughout the first 24 months follow up period completion
PK：Maximal plasma concentration (Cmax)	Cmax of C-CAR168 in peripheral blood	Throughout the first 24 months follow up period completion
PD: Depletion of peripheral blood B cells, plasma cells, and CD20dim T cells		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: The Affiliated Hospital of Qingdao University
• Collaborators: Shanghai AbelZeta Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): October 1, 2028

Study Registration Dates

• First Submitted: June 24, 2026
• First Submitted That Met QC Criteria: June 24, 2026
• First Posted (Actual): June 30, 2026

Study Record Updates

• Last Update Posted (Actual): June 30, 2026
• Last Update Submitted That Met QC Criteria: June 24, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: CD20/BCMA-directed CAR-T cells
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Site; Neoplasms; Neuromuscular Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Eye Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Neurodegenerative Diseases; Skin Diseases; Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Paraneoplastic Syndromes; Neuromuscular Junction Diseases; Myelitis, Transverse; Optic Neuritis; Optic Nerve Diseases; Cranial Nerve Diseases; Skin and Connective Tissue Diseases; Lupus Erythematosus, Systemic; Multiple Sclerosis; Myasthenia Gravis; Neuromyelitis Optica; Scleroderma, Systemic
• Other Study ID Numbers: 1141-049

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