Autoimmune Encephalitis, Chronic Inflammatory Demyelinating Polyradiculoneuropathy, Multiple Sclerosis, Myasthenia Gravis, Neuromyelitis Optica Spectrum Disorders
Conditions
Keywords
Universal Allogeneic CAR T-cells
Brief summary
This is an open label, single-site, dose-escalation study in up to 12 participants with relapsed or refractory Neurological Autoimmune Diseases. This study aims to evaluate the safety and efficacy of the treatment with universal CD19/BCMA CAR T-cells.
Detailed description
This is an investigator-initiated trial to evaluate the safety and efficacy of universal CD19/BCMA CAR T-cells in Relapsed or Refractory Neurological Autoimmune Diseases. Study intervention consists of a single infusion of universal CAR T-cells administered intravenously after a lymphodepleting therapy regimen consisting of fludarabine and cyclophosphamide. Interim analysis will be performed when participants finish the visit 90 days after CAR T-cell infusion.
Interventions
DRUGUCAR T-cell
Universal allogeneic anti-CD19/BCMA CAR T-cells
Sponsors
Shanghai Xiniao Biotech Co., Ltd.
Tianjin Huanhu Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years. * Flow cytometry detected positive B cell CD19 or BCMA in the patient's peripheral blood. * Subjects with relapsed or refractory neurological autoimmune diseases, Including neuromyelitis optica spectrum disorders(NMOSD), myasthenia gravis(MG), multiple sclerosis(MS)，Autoimmune encephalitis(AE) and chronic inflammatory demyelinating Polyradiculoneuropathy(CIDP). * Female subjects of childbearing potential and male subjects with partners of childbearing potential must use medically approved contraception or abstinence during the study treatment period and for at least 6 months after the end of the study treatment; Female subjects of childbearing potential must have a negative Human chorionic gonadotropin (HCG) test within 7 days before study enrollment and not be lactating. * Willing to participate in this clinical study, sign an informed consent form, have good compliance, and cooperate with follow-up.
Exclusion criteria
* Subjects with a history of severe drug allergies or allergic tendencies. * History of malignancy within five years. * Subjects with insufficient cardiac function. * Subjects who are positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with peripheral blood HBV DNA \>the upper limit of detection; subjects positive for hepatitis C virus (HCV) antibody and peripheral blood HCV RNA; individuals positive for human immunodeficiency virus (HIV) antibody; individuals positive for syphilis testing. * Pregnant women or women planning to conceive.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The number and severity of dose-limiting toxicity (DLT) events | Within 28 Days After UCAR T-cell Infusion | DLT will be graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0, and the ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells. |
| The total number, incidence, and severity of AEs | Up to 90 days After UCAR T-cell Infusion | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| MG: Quantitative Myasthenia Gravis Score (QMG) | Up to 24 Months After UCAR T-cell Infusion | The QMG score is a 13-item scale used to quantify disease severity in myasthenia gravis. The scale measures ocular, bulbar, respiratory, and limb function, grading each finding, and ranges from 0 (no myasthenic findings) to 39 (maximal myasthenic deficits). |
| MG: Myasthenia Gravis Activities if Daily Living (MG-ADL) Score | Up to 24 Months After UCAR T-cell Infusion | The MG-ADL is an eight-question survey of symptom severity, with each response graded from 0 (normal) to 3 (most severe). Two questions concern ocular, three oropharyngeal, one respiratory, and two extremity functions. Cumulative MG-ADL scores range from 0 to 24 |
| NMOSD、MS: Expanded Disability Status Scale (EDSS) score | Up to 24 Months After UCAR T-cell 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 is a scale for assessing neurologic impairment in multiple sclerosis (MS). It 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 from MS). A negative change from baseline indicates improvement. A participant was considered to have a worsening in overall EDSS score of at least 2 if baseline EDSS score was 0, or at least 1 point if baseline EDSS score is 1 to 5, or at least 0.5 point if baseline EDSS score is 5.5 or more. |
| AE: Change in CASE | Up to 24 Months After UCAR T-cell Infusion | The changes of Clinical Assessment Scale in Autoimmune Encephalitis (CASE) score from baseline. |
| CIDP: Inflammatory Neuropathy Cause and Treatment (INCAT) Score | Up to 24 Months After UCAR T-cell Infusion | The INCAT score comprises two parts, the arm score and the leg score. Based on a patient's level of impairment in their arms and legs, each part is scored between 0 and 5 points, resulting in an INCAT total score between 0 and 10. |
| NMOSD、MS: Modified Rankin Scale | Up to 24 Months After UCAR T-cell Infusion | Modified Rankin Scale (mRS) is a profoundly valid and reliable measure of disability and is broadly utilized for assessing stroke outcomes and degree of disability. We characterized a favorable outcome as mRS ranging from zero up to two, while unfavorable outcome ranging for 3 up to 6. |
Countries
China
Contacts
Primary ContactJialing Wu
Backup ContactGuanen Zhou
Outcome results
None listed