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

Phase 1

Recruiting

• Conditions: Systemic Lupus Erythematosus (SLE); Immune-Mediated Necrotizing Myopathy; Neuromyelitis Optica Spectrum Disorders; Multiple Sclerosis-Relapsing-Remitting; Myasthenia Gravis
• Interventions: Biological: CD20/BCMA-directed CAR-T cells

• Registration Number: NCT06249438
• Lead Sponsor: RenJi Hospital

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-01-21
• Study First Submitted QC: 2024-01-31
• Study First Posted: 2024-02-08
• Study Start: 2024-03-20
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-20
• Last Update Posted: 2024-10-22
• Primary Completion: 2027-03
• Study Completion: 2040-03

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

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) 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 at least two immunosuppressants (immunosuppressants or disease-modifying drug (DMD) for MS participants).
• 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.
• 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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
C-CAR168	CD20/BCMA-directed CAR-T cells	Autologous C-CAR168 administered by intravenous (IV) infusion

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
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)
The clearance of peripheral blood B cell	Throughout the first 24 months follow up period completion (3 years)
Time to response (TTR)	Throughout the first 24 months follow up period completion (3 years)	The time from the date of C-CAR168 infusion to the first documented remission
Time to reach the maximal plasma concentration (Tmax)	Throughout the first 24 months follow up period completion (3 years)	Time to reach the maximal plasma concentration of C-CAR168 in peripheral blood
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)
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 achieved remission at 6 months (6M)	Throughout the first 6 months follow up period completion (1.5 years)
The proportion of subjects who experienced relapse during the main study period	Throughout the first 24 months follow up period completion (3 years)
Progression-free survival (PFS)	Throughout the first 24 months follow up period completion (3 years)	The time from the date of C-CAR168 infusion to the date of first documented disease progression or death, whichever comes first
Maximal plasma concentration (Cmax)	Throughout the first 24 months follow up period completion (3 years)	Maximal plasma concentration of C-CAR168 in peripheral blood
Duration in peripheral blood (Tlast)	Throughout the first 24 months follow up period completion (3 years)	The duration of C-CAR168 in peripheral blood
Area under curve (AUC)	Throughout the first 24 months follow up period completion (3 years)	Area under the curve of C-CAR168 in peripheral blood
The decline of serum immunoglobulin	Throughout the first 24 months follow up period completion (3 years)

Trial Locations

Locations (1)

Department of Rheumatology, RenJi Hospital, School of Medicine, Shanghai JiaoTong University; 🇨🇳 Shanghai, Shanghai, China