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

Systemic Lupus Erythematosus (SLE) Clinical Trial

— CAR-AID  

Official title:

An Exploratory Clinical Study of Anti-B-cell Maturation Antigen(BCMA)/Cluster of Differentiation Antigen 20(CD20) Chimeric Antigen Receptor Autologous T Cell Product (C-CAR168) in the Treatment of Autoimmune Diseases Refractory to Standard Therapy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06249438
• Other study ID #: 1141-043(CAR-AID)
• Status: Recruiting
• Phase: Phase 1
• Start date: March 20, 2024
• Est. completion date: March 2040

Study information

• Verified date: March 2024
• Source: RenJi Hospital
• Contact: Nan Shen, MD & PhD
• Phone: +86-21-63260477
• Email: nanshensibs[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: March 2040
• Est. primary completion date: March 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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) 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.

• 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.

• 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.

Related Conditions & MeSH terms

• Autoimmune Diseases
• Immune-Mediated Necrotizing Myopathy
• Lupus Erythematosus, Systemic
• Multiple Sclerosis
• Multiple Sclerosis-Relapsing-Remitting
• Neuromyelitis Optica
• Neuromyelitis Optica Spectrum Disorders
• Systemic Lupus Erythematosus (SLE)

Intervention

Biological:
• CD20/BCMA-directed CAR-T cells
Autologous 2nd generation CD20/BCMA-directed CAR-T cells, single infusion intravenously

Locations

Country	Name	City	State
China	Department of Rheumatology, RenJi Hospital, School of Medicine, Shanghai JiaoTong University	Shanghai	Shanghai

Sponsors (2)

Lead Sponsor	Collaborator
RenJi Hospital	AbelZeta Pharma Inc.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Serum cytokines (including Interleukin (IL)-2, IL-4, IL-6, IL-10, Tumor Necrosis Factor (TNF)-a, Interferon (IFN)-?) changes	Detection of serum cytokines (including IL-2, IL-4, IL-6, IL-10, TNF-a, IFN-?) changes over time by flow cytometry	Throughout the first 24 months follow up period completion (3 years)
Other	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)
Other	B cells changes in bone marrow, muscle or kidney	Detection of B cells concentration changes in bone marrow, muscle or kidney by flow cytometry	Throughout the first 24 months follow up period completion (3 years)
Other	Plasma cells or long-lived plasma cells changes in bone marrow, muscle or kidney	Detection of plasma cells or long-lived plasma cells concentration changes in bone marrow, muscle or kidney by flow cytometry	Throughout the first 24 months follow up period completion (3 years)
Primary	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
Primary	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	The proportion of subjects who achieved remission at 6 months (6M)		Throughout the first 6 months follow up period completion (1.5 years)
Secondary	The proportion of subjects who achieved remission during the main study period		Throughout the first 24 months follow up period completion (3 years)
Secondary	The proportion of subjects who experienced relapse during the main study period		Throughout the first 24 months follow up period completion (3 years)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Maximal plasma concentration (Cmax)	Maximal plasma concentration of C-CAR168 in peripheral blood	Throughout the first 24 months follow up period completion (3 years)
Secondary	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)
Secondary	Duration in peripheral blood (Tlast)	The duration of C-CAR168 in peripheral blood	Throughout the first 24 months follow up period completion (3 years)
Secondary	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)
Secondary	The clearance of peripheral blood B cell		Throughout the first 24 months follow up period completion (3 years)
Secondary	The decline of serum immunoglobulin		Throughout the first 24 months follow up period completion (3 years)
Secondary	The elevation of peripheral blood complement		Throughout the first 24 months follow up period completion (3 years)
Secondary	The decline of autoantibodies or other disease specific biomarkers		Throughout the first 24 months follow up period completion (3 years)