Clinical trial NCT06249438: A Study of C-CAR168 in the Treatment of Autoimmune Diseases Refractory to Standard Therapy
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Systemic Lupus Erythematosus (SLE)
Immune-Mediated Necrotizing Myopathy
Neuromyelitis Optica Spectrum Disorders
Multiple Sclerosis-Relapsing-Remitting
Myasthenia Gravis
Keywords: CD20/BCMA-directed CAR-T cells
Lead sponsor: RenJi Hospital
Sponsor class: OTHER
Collaborators: name: AbelZeta Pharma Inc.
First posted: 2024-02-08
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of Adverse Events [Safety and Tolerability]
timeFrame: Throughout the first 24 months follow up period completion (3 years)，DLTs will be observed/collected throughout the 28 days post C-CAR168 infusion
measure: The subsequent recommended dose of C-CAR168 in patients with autoimmune diseases refractory to standard therapy
timeFrame: Throughout the first 24 months follow up period completion (3 years)
Secondary outcomes:
measure: The proportion of subjects who achieved remission at 6 months (6M)
timeFrame: Throughout the first 6 months follow up period completion (1.5 years)
measure: The proportion of subjects who achieved remission during the main study period
timeFrame: Throughout the first 24 months follow up period completion (3 years)
measure: The proportion of subjects who experienced relapse during the main study period
timeFrame: Throughout the first 24 months follow up period completion (3 years)
measure: Time to response (TTR)
timeFrame: Throughout the first 24 months follow up period completion (3 years)
measure: Progression-free survival (PFS)
timeFrame: Throughout the first 24 months follow up period completion (3 years)
measure: The proportion of subjects who achieved glucocorticoids/immunosuppressant free and subjects who achieved low-dose glucocorticoids application during the main study period
timeFrame: Throughout the first 24 months follow up period completion (3 years)
measure: Maximal plasma concentration (Cmax)
timeFrame: Throughout the first 24 months follow up period completion (3 years)
measure: Time to reach the maximal plasma concentration (Tmax)
timeFrame: Throughout the first 24 months follow up period completion (3 years)
measure: Duration in peripheral blood (Tlast)
timeFrame: Throughout the first 24 months follow up period completion (3 years)
measure: Area under curve (AUC)
timeFrame: Throughout the first 24 months follow up period completion (3 years)
measure: The clearance of peripheral blood B cell
timeFrame: Throughout the first 24 months follow up period completion (3 years)
measure: The decline of serum immunoglobulin
timeFrame: Throughout the first 24 months follow up period completion (3 years)
measure: The elevation of peripheral blood complement
timeFrame: Throughout the first 24 months follow up period completion (3 years)
measure: The decline of autoantibodies or other disease specific biomarkers
timeFrame: Throughout the first 24 months follow up period completion (3 years)
Other outcomes:
measure: Serum cytokines (including Interleukin (IL)-2, IL-4, IL-6, IL-10, Tumor Necrosis Factor (TNF)-α, Interferon (IFN)-γ) changes
timeFrame: Throughout the first 24 months follow up period completion (3 years)
measure: Soluble BCMA changes in peripheral blood
timeFrame: Throughout the first 24 months follow up period completion (3 years)
measure: B cells changes in bone marrow, muscle or kidney
timeFrame: Throughout the first 24 months follow up period completion (3 years)
measure: Plasma cells or long-lived plasma cells changes in bone marrow, muscle or kidney
timeFrame: Throughout the first 24 months follow up period completion (3 years)
measure: RNA changes in peripheral blood
timeFrame: Throughout the first 24 months follow up period completion (3 years)
Locations:
city: Shanghai
country: China
facility: Department of Rheumatology, RenJi Hospital, School of Medicine, Shanghai JiaoTong University
state: Shanghai
Study officials:
affiliation: Department of Rheumatology, RenJi Hospital, School of Medicine, Shanghai JiaoTong University
name: Nan Shen, MD & PhD
role: PRINCIPAL_INVESTIGATOR
References: