Chronic Inflammatory Demyelinating Polyradiculoneuropathy, Multiple Sclerosis, Myasthenia Gravis, Generalized, Neuromyelitis Optica Spectrum Disorders
Conditions
Keywords
universal CAR-T, Neuromyelitis Optica Spectrum Disorders, Myasthenia Gravis, Multiple Sclerosis, Chronic Inflammatory Demyelinating Polyradiculoneuropathy
Brief summary
This is an open label, single-site, dose-escalation study in up to 25 participants with refractory autoimmune diseases of nervous system. This study aims to evaluate the safety and efficacy of the treatment with universal BCMA and CD19 CART.
Interventions
DRUGUniversal BCMA CAR-T
Universal BCMA CAR-T
DRUGUniversal CD19 CAR-T
Universal CD19 CAR-T
DRUGUniversal BCMA CAR-T; Universal CD19 CAR-T
Universal BCMA CAR-T; Universal CD19 CAR-T
Sponsors
Bioray Laboratories
Xuanwu Hospital, Beijing
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Aged 18-75 years (for MS patients, 18-55 years); both genders eligible. * Subjects with refractory neurological autoimmune diseases who have failed standard treatment or lack effective treatment, Including neuromyelitis optica spectrum disorders(NMOSD), generalized myasthenia gravis(gMG), chronic inflammatory demyelinating Polyradiculoneuropathy(CIDP) and multiple sclerosis(MS). * Anticipated survival of ≥ 12 weeks as judged by the researcher. * Agrees to use double barrier methods, condoms, oral or injectable contraceptives, or intrauterine devices during the study period and for one year after taking the study medication. * Provides written informed consent.
Exclusion criteria
* History of solid organ transplantation. * Malignant tumor within the last two years. * Positive for Hepatitis B surface antigen (HBsAg) or Hepatitis B core antibody (HBcAb), with peripheral blood Hepatitis B virus (HBV) DNA detected as positive; positive for Hepatitis C virus antibodies, with peripheral blood Hepatitis C virus RNA detected as positive; positive for Human Immunodeficiency Virus (HIV) antibodies; positive for Cytomegalovirus (CMV) DNA; positive for syphilis. * Primary immunodeficiency (congenital or acquired). * Severe cardiac disease. * History of psychiatric disorders or history of psychotropic drug abuse, with no history of withdrawal. * Allergic constitution or a history of severe allergies. * Pregnant or breastfeeding women.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of dose-limiting toxicities(DLTs) | First 28 days after infusion | Incidence of dose-limiting toxicities(DLTs) |
| Incidence of adverse events(AEs) and severe adverse | Up to 12 months after infusion | Incidence of adverse events(AEs) and severe adverse events(SAEs). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| MS: Changes of the number of Gd-enhancing T1 Lesions | 6, 12months | The changes of enhancing Lesions as detected by brain Magnetic Resonance Imaging (MRI) |
| Concentrations of UCAR-T cells | 3 months | The concentration of BCMA UCAR T cells and CD19 UCAR-T cells in peripheral blood after infusion |
| B cell levels in peripheral blood | 3 months | The change of B cell levels in peripheral blood after infusion |
| MS: Changes of the number of Number of New or Enlarging T2 Lesions | 6, 12months | Number of new/enlarging T2 lesions on last available MRI scan compared to baseline. |
| NMOSD: Annualized relapse rate | 6, 12months | ARR is defined as the number of relapses divided by the total participant-years after infusion |
| gMG: Changes of Myasthenia Gravis Activities if Daily Living (MG-ADL) Score | 1, 3, 6, 12months | MG-ADL scale assesses the impact of gMG on daily functions by measuring 8 signs or symptoms that are commonly affected in gMG. Each item is measured on a 4-point scale, where a score of 0 represents normal function and a score of 3 represents the loss of ability to perform that function. Total scores range from 0 to 24 points, with a higher score showing more severe gMG. |
| Changes of pathogenic antibody titers after infusion | 1, 3, 6 ,12months | The changes of pathogenic antibody titers in peripheral blood or cerebrospinal fluid. |
| CIDP:Changes of Inflammatory Neuropathy Cause and Treatment (INCAT) Score after infusion. | 1, 3, 6, 12months | The INCAT score assesses the functionality of the arms and legs by giving a 0-5 score for arms and legs, with 0 representing no disability and 5 representing no arm function or inability to stand/walk. |
Countries
China
Contacts
Primary ContactJunwei Hao, MD;PhD
Outcome results
None listed