Autoimmune Encephalitis, Multiple Sclerosis (MS), Neuromyelitis Optica Spectrum Disorders (NMOSD), Stiff Person Syndrome
Conditions
Keywords
CD20/BCMA-directed CAR-T cells
Brief summary
This is an investigator-initiated, single-center, open-label study of C-CAR168, an autologous bi-specific CAR-T therapy targeting CD20 and BCMA, for the treatment of adult patients with central nervous system 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
Shanghai AbelZeta Ltd.
Huashan Hospital
Study design
Allocation
NA
Intervention model
SEQUENTIAL
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 Multiple Sclerosis (MS)/Neuromyelitis Optica Spectrum Disorders (NMOSD)/Autoimmune Encephalitis(AiE)/Stiff Person Spectrum Disorder(SPSD) according to recognized diagnostic criteria for at least 6 months. * Prior treatment failure with standard therapy. * 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. * A history of ≥ Grade 2 bleeding within 4 weeks 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. * Any contraindication to lumbar puncture.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The subsequent recommended dose of C-CAR168 in patients with central nervous system autoimmune diseases refractory to standard therapy | Throughout the first 24 months follow up period completion | Based on the assessment of overall safety profile |
| Incidence and severity of Adverse Events [Safety and Tolerability] | Throughout the first 3 months follow up period completion | Incidence and severity of adverse events (AE) and serious adverse events (SAE) within three months following infusion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| MS: No Evidence of Disease Activity-3 (NEDA-3) | Throughout the first 24 months follow up period completion | Proportion of participants achieving NEDA-3 at 6 months post-infusion and during the study period |
| MS and NMOSD: Expanded Disability Status Scale (EDSS) | Throughout the first 24 months follow up period completion | Change from baseline in EDSS at 6 months and 24 months post-infusion. EDSS and its associated functional system (FS) score provide a system for quantifying disability and monitoring changes in the level of disability over time. EDSS consists of 7 FS (visual FS, brainstem FS, pyramidal FS, cerebellar FS, sensory FS, bowel and bladder FS, and cerebral FS) which are used to derive EDSS score ranging from 0 (normal neurological exam) to 10 (death). |
| MS and NMOSD: MRI | Throughout the first 24 months follow up period completion | Number of T1 gadolinium-enhancing lesions and new or enlarging T2 lesions, as well as their change from baseline, at 6 months and 24 months post-infusion. Change from baseline in total T2 lesion volume, gray matter volume (GMV), white matter volume (WMV), and brain volume (BV), as well as annualized-brain volume loss (a-BVL), at 6 months and 24 months post-infusion |
| Autoimmune Encephalitis (AiE): Clinical Assessment Scale in Autoimmune Encephalitis (CASE) | Throughout the first 24 months follow up period completion | Change from baseline in CASE at 6 months and 24 months post-infusion. The Clinical Assessment Scale in Autoimmune Encephalitis (CASE) has a score range from 0 to 27, and higher scores indicate a worse clinical outcome. |
| MS, NMOSD and AiE: Annualized Relapse Rate (ARR) | Throughout the first 24 months follow up period completion | ARR at 6 months and 24 months post-infusion |
| Stiff-Person Syndrome (SPS): Distribution of Stiffness Index (DSI) | Throughout the first 24 months follow up period completion | Change from baseline in DSI at 6 months and 24 months post-infusion. Distribution of Stiffness Index (DSI) is a validated indicator or stiffness. Scores range from 0 to 6 and reflect the extent of stiffness. Higher scores indicate a worse outcome. |
| Incidence and severity of adverse events (AE) | Throughout the first 24 months follow up period completion | Incidence and severity of adverse events (AE) and serious adverse events (SAE) during the study |
| PK: Area under curve (AUC) | Throughout the first 24 months follow up period completion | AUC of C-CAR168 in peripheral blood |
| Pharmacodynamics (PD): Depletion of peripheral blood B cells, plasma cells, and CD20dim T cells | Throughout the first 24 months follow up period completion | — |
| PD: Decline of serum immunoglobulin | Throughout the first 24 months follow up period completion | — |
| SPS: Heightened Sensitivity Score (HSS) | Throughout the first 24 months follow up period completion | Change from baseline in HSS at 6 months and 24 months post-infusion. Heightened Sensitivity Score (HSS) measures changes in the frequency of spasms. Scores range from 0 to 7. Higher scores indicate a worse outcome. |
| Pharmacokinetics (PK): Maximal plasma concentration (Cmax) | Throughout the first 24 months follow up period completion | Cmax of C-CAR168 in peripheral blood |
| PK: Time to reach the maximal plasma concentration (Tmax) | Throughout the first 24 months follow up period completion | Tmax of C-CAR168 in peripheral blood |
| PK: Duration in peripheral blood (Tlast) | Throughout the first 24 months follow up period completion | Tlast of C-CAR168 in peripheral blood |
Other
| Measure | Time frame | Description |
|---|---|---|
| Serum cytokines changes | Throughout the first 24 months follow up period completion | Detection of serum cytokines changes over time by flow cytometry |
| Soluble BCMA changes in peripheral blood | Throughout the first 24 months follow up period completion | Detection of soluble BCMA changes in peripheral blood by Enzyme Linked ImmunoSorbent Assay (ELISA) |
| Changes in CSF CAR DNA copy number and CAR-T cells | Throughout the first 24 months follow up period completion | Detection of changes in CSF CAR DNA copy number and CAR-T cells by quantitative polymerase chain reaction (qPCR) and flow cytometry |
Contacts
Primary ContactXiangjun Chen
Outcome results
None listed