MuSK Myasthenia Gravis
Conditions
Keywords
CAAR-T (Chimeric Autoantibody Receptor T Cells) Therapy, CAR-T (Chimeric Antigen Receptor T Cells) Therapy, Cell Therapy, Autoimmune Disease, Autoimmunity, Immunotherapy, Adoptive, Immune System Diseases, Myasthenia Gravis (MG), Muscle-specific tyrosine kinase (MuSK), Muscle Weakness, Neuromuscular Diseases, Musculoskeletal Diseases
Brief summary
Muscle-specific tyrosine kinase (MuSK) myasthenia gravis (MG) is a rare but potentially severe disease, in which patients develop pathogenic autoantibodies that specifically target the MuSK protein in the neuromuscular junction. This phase 1 study is being conducted to evaluate the safety of various dosing regimens of an investigational cell therapy, MuSK-CAART, that can be given to patients with anti-MuSK antibody positive Myasthenia Gravis (MuSK MG), who have active disease. Various dosing regimens of MuSK-CAART alone, in combination with cyclophosphamide (CY), and in combination with CY and fludarabine (FLU) will be evaluated. Treatment with MuSK-CAART may potentially lead to complete and durable remission of disease.
Interventions
BIOLOGICALMuSK-CAART
Intravenous infusion of MuSK-CAART at different doses. Subjects may also receive MuSK-CAART following pre-treatment with CY, or CY plus FLU.
Sponsors
Cabaletta Bio
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
* Confirmed diagnosis of MuSK-type MG with at least 1 prior positive anti-MuSK antibody test. * History of a negative anti-AChR (acetylcholine receptor) antibody test. * Positive anti-MuSK antibody test at screening * MG severity Class I to IVa on the MGFA (Myasthenia Gravis Foundation of America) Clinical Classification
Exclusion criteria
* Rituximab in the last 12 months. * Prednisone \> 0.25mg/kg/day \[in Part A\] * Other autoimmune disorder requiring immunosuppressive therapies. * Investigational treatment for MG in the past 12 weeks. * Absolute lymphocyte count \< 500/µL at screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events | 3 months | Incidence of adverse events (AEs), including dose-limiting toxicities (DLTs) and AEs that are related to MuSK-CAART. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total MuSK-CAART positive cells | Baseline | Total MuSK-CAART positive cells for each manufacturing run. |
| Percent of CAAR-transduced cells | Baseline | Percent of total cells for infusion that are CAAR (Chimeric Autoantibody Receptor)-transduced cells. |
| Cellular kinetics profile of MuSK-CAART | Up to 36 months | Cellular kinetics profile of MuSK-CAART after infusion. |
| Change in MuSK autoantibody titer | Up to 36 months | Change in MuSK autoantibody titer compared to pre-infusion visit by clinically validated assay. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Use of Concomitant Therapies | Up to 36 months | Frequency and dose of concomitant therapies. |
| Measurement of Clinical Symptoms using MG-ADL | Up to 36 months | Measurement of clinical symptoms using the Myasthenia Gravis Activities of Daily Living (MG-ADL) assessment. |
| Measurement of Clinical Symptoms using QMG | Up to 36 months | Measurement of clinical symptoms using the Quantitative Myasthenia Gravis (QMG) assessment. |
| Measurement of Clinical Symptoms using MGC | Up to 36 months | Measurement of clinical symptoms using the Myasthenia Gravis Composite (MGC) assessment. |
| Measurement of Quality of Life (QoL) using MG-QOL-15r | Up to 36 months | Measurement of Quality of Life using the MG-QOL-15r (Myasthenia Gravis Qualify of Life 15-item scale, revised) questionnaire. |
Countries
United States
Outcome results
None listed