A Study of C-CAR168 in the Treatment of Autoimmune Diseases Refractory to Standard Therapy (CAR-AID)

An Exploratory Clinical Study of Cluster of Differentiation Antigen 20(CD20)/Anti-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, multicenter, 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: Recruiting
• Conditions: Myasthenia Gravis; Systemic Lupus Erythematosus (SLE); Multiple Sclerosis (MS); Systemic Sclerosis (SSc); Immune-mediated Necrotizing Myopathy (IMNM); Neuromyelitis Optica Spectrum Disorders (NMOSD)
• Intervention / Treatment: Biological: CD20/BCMA-directed CAR-T cells

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Nan Shen, MD & PhD; Phone Number: +86-21-63260477; Email: nanshensibs@gmail.com
• Study Contact Backup: Name: Huihua Ding, MD; Phone Number: +86-21-53882280; Email: dinghuihua@outlook.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200001
      • Recruiting
      • Department of Rheumatology, RenJi Hospital, School of Medicine, Shanghai JiaoTong University
      • Contact: Nan Shen, MD & PhD; Phone Number: +86-21-63260477; Email: nanshensibs@gmail.com
      • Contact: Huihua Ding, MD; Phone Number: +86-21-53882280; Email: dinghuihua@outlook.com
      • Principal Investigator: Nan Shen, MD & PhD
      • Principal Investigator: Huihua Ding, MD

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 SLE/Immune-Mediated Necrotizing Myopathy (IMNM)/Neuromyelitis Optica Spectrum Disorders (NMOSD)/Multiple Sclerosis (MS)/Myasthenia Gravis (MG)/Systemic Sclerosis (SSc) according to recognized diagnostic criteria for at least 6 months.
• Remains disease active or relapses after treatment with standard of care therapy for at least 8 weeks with the dose stable for more than 2 weeks; patients should have been treated with at least two immunosuppressants (including immunosuppressants, biologics, and disease-modifying drug (DMD) ).
• 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.
• ≥ Grade 2 bleeding within the past 30 days 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.

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: 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 of Adverse Events [Safety and Tolerability]	Incidence of any adverse events (AEs), including dose limiting toxicities (DLTs)	Throughout the first 24 months follow up period completion (3 years)，DLTs will be observed/collected throughout the 28 days post C-CAR168 infusion
The subsequent recommended dose of C-CAR168 in patients with autoimmune diseases refractory to standard therapy	Based on the assessment of dose-limiting toxicities (DLTs) rates and overall safety profile	Throughout the first 24 months follow up period completion (3 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of subjects who achieved remission at 6 months (6M)		Throughout the first 6 months follow up period completion (1.5 years)
The proportion of subjects who achieved remission during the main study period		Throughout the first 24 months follow up period completion (3 years)
The proportion of subjects who experienced relapse during the main study period		Throughout the first 24 months follow up period completion (3 years)
Time to response (TTR)	The time from the date of C-CAR168 infusion to the first documented remission	Throughout the first 24 months follow up period completion (3 years)
Progression-free survival (PFS)	The time from the date of C-CAR168 infusion to the date of first documented disease progression or death, whichever comes first	Throughout the first 24 months follow up period completion (3 years)
The proportion of subjects who achieved glucocorticoids/immunosuppressant free and subjects who achieved low-dose glucocorticoids application during the main study period		Throughout the first 24 months follow up period completion (3 years)
Maximal plasma concentration (Cmax)	Maximal plasma concentration of C-CAR168 in peripheral blood	Throughout the first 24 months follow up period completion (3 years)
Time to reach the maximal plasma concentration (Tmax)	Time to reach the maximal plasma concentration of C-CAR168 in peripheral blood	Throughout the first 24 months follow up period completion (3 years)
Duration in peripheral blood (Tlast)	The duration of C-CAR168 in peripheral blood	Throughout the first 24 months follow up period completion (3 years)
Area under curve (AUC)	Area under the curve of C-CAR168 in peripheral blood	Throughout the first 24 months follow up period completion (3 years)
The clearance of peripheral blood B cell		Throughout the first 24 months follow up period completion (3 years)
The decline of serum immunoglobulin		Throughout the first 24 months follow up period completion (3 years)
The elevation of peripheral blood complement		Throughout the first 24 months follow up period completion (3 years)
The decline of autoantibodies or other disease specific biomarkers		Throughout the first 24 months follow up period completion (3 years)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum cytokines (including Interleukin (IL)-2, IL-4, IL-6, IL-10, Tumor Necrosis Factor (TNF)-α, Interferon (IFN)-γ) changes	Detection of serum cytokines (including IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ) changes over time by flow cytometry	Throughout the first 24 months follow up period completion (3 years)
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 (3 years)
RNA changes in peripheral blood	Detection of RNA changes in peripheral blood by RNA sequencing	Throughout the first 24 months follow up period completion (3 years)
Protective antibodies changes in peripheral blood	Detection of protective antibodies changes in peripheral blood by ELISA	Throughout the first 24 months follow up period completion (3 years)
B cells changes in bone marrow, skin, muscle or kidney	Detection of B cells concentration changes in bone marrow, skin, muscle or kidney by flow cytometry	Throughout the first 24 months follow up period completion (3 years)
Plasma cells or long-lived plasma cells changes in bone marrow, skin, muscle or kidney	Detection of plasma cells or long-lived plasma cells concentration changes in bone marrow, skin, muscle or kidney by flow cytometry	Throughout the first 24 months follow up period completion (3 years)

Collaborators and Investigators

• Sponsor: RenJi Hospital
• Collaborators: AbelZeta Pharma Inc.
• Investigators: Principal Investigator: Nan Shen, MD & PhD, Department of Rheumatology, RenJi Hospital, School of Medicine, Shanghai JiaoTong University

Study record dates

Study Major Dates

• Study Start (Actual): March 20, 2024
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2040

Study Registration Dates

• First Submitted: January 21, 2024
• First Submitted That Met QC Criteria: January 31, 2024
• First Posted (Actual): February 8, 2024

Study Record Updates

• Last Update Posted (Actual): July 25, 2025
• Last Update Submitted That Met QC Criteria: July 21, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: CD20/BCMA-directed CAR-T cells
• Additional Relevant MeSH Terms: Nervous System Diseases; Pathologic Processes; Neoplasms by Site; Neoplasms; Neuromuscular Diseases; Connective Tissue 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; Lupus Erythematosus, Systemic; Multiple Sclerosis; Sclerosis; Myasthenia Gravis; Neuromyelitis Optica; Autoimmune Diseases; Scleroderma, Systemic
• Other Study ID Numbers: 1141-043(CAR-AID)

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