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| Name | Class |
|---|---|
| Shanghai AbelZeta Ltd. | INDUSTRY |
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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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| C-CAR168 | Experimental | Autologous C-CAR168 administered by intravenous (IV) infusion |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CD20/BCMA-directed CAR-T cells | Biological | Autologous 2nd generation CD20/BCMA-directed CAR-T cells, single infusion intravenously |
|
| Measure | Description | Time Frame |
|---|---|---|
| Incidence and severity of Adverse Events [Safety and Tolerability] | Incidence and severity of adverse events (AE) and serious adverse events (SAE) within three months following infusion | Throughout the first 3 months follow up period completion |
| The subsequent recommended dose of C-CAR168 in patients with central nervous system autoimmune diseases refractory to standard therapy | Based on the assessment of overall safety profile | Throughout the first 24 months follow up period completion |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence and severity of adverse events (AE) | Incidence and severity of adverse events (AE) and serious adverse events (SAE) during the study | Throughout the first 24 months follow up period completion |
| MS: No Evidence of Disease Activity-3 (NEDA-3) |
| Measure | Description | Time Frame |
|---|---|---|
| Serum cytokines changes | Detection of serum cytokines changes over time by flow cytometry | Throughout the first 24 months follow up period completion |
| Soluble BCMA changes in peripheral blood | Detection of soluble BCMA changes in peripheral blood by Enzyme Linked ImmunoSorbent Assay (ELISA) |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Xiangjun Chen | Contact | +86 21 52888159 | xiangjchen@fudan.edu.cn |
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Proportion of participants achieving NEDA-3 at 6 months post-infusion and during the study period
| Throughout the first 24 months follow up period completion |
| MS and NMOSD: Expanded Disability Status Scale (EDSS) | 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). | Throughout the first 24 months follow up period completion |
| MS and NMOSD: MRI | 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 | Throughout the first 24 months follow up period completion |
| Autoimmune Encephalitis (AiE): Clinical Assessment Scale in Autoimmune Encephalitis (CASE) | 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. | Throughout the first 24 months follow up period completion |
| MS, NMOSD and AiE: Annualized Relapse Rate (ARR) | ARR at 6 months and 24 months post-infusion | Throughout the first 24 months follow up period completion |
| Stiff-Person Syndrome (SPS): Distribution of Stiffness Index (DSI) | 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. | Throughout the first 24 months follow up period completion |
| SPS: Heightened Sensitivity Score (HSS) | 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. | Throughout the first 24 months follow up period completion |
| Pharmacokinetics (PK): Maximal plasma concentration (Cmax) | Cmax of C-CAR168 in peripheral blood | Throughout the first 24 months follow up period completion |
| PK: Time to reach the maximal plasma concentration (Tmax) | Tmax of C-CAR168 in peripheral blood | Throughout the first 24 months follow up period completion |
| PK: Duration in peripheral blood (Tlast) | Tlast of C-CAR168 in peripheral blood | Throughout the first 24 months follow up period completion |
| PK: Area under curve (AUC) | AUC of C-CAR168 in peripheral blood | Throughout the first 24 months follow up period completion |
| 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 |
| Throughout the first 24 months follow up period completion |
| Changes in CSF CAR DNA copy number and CAR-T cells | Detection of changes in CSF CAR DNA copy number and CAR-T cells by quantitative polymerase chain reaction (qPCR) and flow cytometry | Throughout the first 24 months follow up period completion |
| ID | Term |
|---|---|
| D009103 | Multiple Sclerosis |
| D009471 | Neuromyelitis Optica |
| D020274 | Autoimmune Diseases of the Nervous System |
| D016750 | Stiff-Person Syndrome |
| ID | Term |
|---|---|
| D020278 | Demyelinating Autoimmune Diseases, CNS |
| D009422 | Nervous System Diseases |
| D003711 | Demyelinating Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D009188 | Myelitis, Transverse |
| D009902 | Optic Neuritis |
| D009901 | Optic Nerve Diseases |
| D003389 | Cranial Nerve Diseases |
| D005128 | Eye Diseases |
| D013118 | Spinal Cord Diseases |
| D002493 | Central Nervous System Diseases |
| D009468 | Neuromuscular Diseases |
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