Immune-mediated Necrotizing Myopathy (IMNM), Multiple Sclerosis (MS), Myasthenia Gravis, Neuromyelitis Optica Spectrum Disorders (NMOSD), Systemic Lupus Erythematosus (SLE), Systemic Sclerosis (SSc)
Conditions
Keywords
CD20/BCMA-directed CAR-T cells
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
Interventions
BIOLOGICALCD20/BCMA-directed CAR-T cells
Autologous 2nd generation CD20/BCMA-directed CAR-T cells, single infusion intravenously
Sponsors
AbelZeta Pharma Inc.
RenJi Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) | — |
| 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 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) | — |
| 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 |
| 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 |
| 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) | — |
| Maximal plasma concentration (Cmax) | Throughout the first 24 months follow up period completion (3 years) | Maximal plasma concentration of C-CAR168 in peripheral blood |
| 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Protective antibodies changes in peripheral blood | Throughout the first 24 months follow up period completion (3 years) | Detection of protective antibodies changes in peripheral blood by ELISA |
| B cells changes in bone marrow, skin, muscle or kidney | Throughout the first 24 months follow up period completion (3 years) | Detection of B cells concentration changes in bone marrow, skin, muscle or kidney by flow cytometry |
| Plasma cells or long-lived plasma cells changes in bone marrow, skin, muscle or kidney | Throughout the first 24 months follow up period completion (3 years) | Detection of plasma cells or long-lived plasma cells concentration changes in bone marrow, skin, muscle or kidney by flow cytometry |
| RNA changes in peripheral blood | Throughout the first 24 months follow up period completion (3 years) | Detection of RNA changes in peripheral blood by RNA sequencing |
| Soluble BCMA changes in peripheral blood | Throughout the first 24 months follow up period completion (3 years) | Detection of soluble BCMA changes in peripheral blood by Enzyme Linked ImmunoSorbent Assay (ELISA) |
| Serum cytokines (including Interleukin (IL)-2, IL-4, IL-6, IL-10, Tumor Necrosis Factor (TNF)-α, Interferon (IFN)-γ) changes | Throughout the first 24 months follow up period completion (3 years) | Detection of serum cytokines (including IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ) changes over time by flow cytometry |
Countries
China
Contacts
Primary ContactNan Shen, MD & PhD
Backup ContactHuihua Ding, MD
Outcome results
None listed