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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| MuSK-CAART | Experimental | Cohort A: Infusion of MuSK-CAART at various dose levels with or without pre-treatment (6 groups planned). Cohort B: Infusion of MuSK-CAART at the dose regimen selected from Part A. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MuSK-CAART | Biological | Intravenous infusion of MuSK-CAART at different doses. Subjects may also receive MuSK-CAART following pre-treatment with CY, or CY plus FLU. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Adverse events | Incidence of adverse events (AEs), including dose-limiting toxicities (DLTs) and AEs that are related to MuSK-CAART. | 3 months |
| Measure | Description | Time Frame |
|---|---|---|
| Total MuSK-CAART positive cells | Total MuSK-CAART positive cells for each manufacturing run. | Baseline |
| Percent of CAAR-transduced cells | Percent of total cells for infusion that are CAAR (Chimeric Autoantibody Receptor)-transduced cells. |
| Measure | Description | Time Frame |
|---|---|---|
| Use of Concomitant Therapies | Frequency and dose of concomitant therapies. | Up to 36 months |
| Measurement of Clinical Symptoms using MG-ADL | Measurement of clinical symptoms using the Myasthenia Gravis Activities of Daily Living (MG-ADL) assessment. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Cabaletta Bio | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UC Irvine, Department of Neurology | Orange | California | 92868 | United States | ||
| UC Davis, Department of Neurology |
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| ID | Term |
|---|---|
| D009157 | Myasthenia Gravis |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D018908 | Muscle Weakness |
| D009468 | Neuromuscular Diseases |
| D009140 | Musculoskeletal Diseases |
| ID | Term |
|---|---|
| D020361 | Paraneoplastic Syndromes, Nervous System |
| D009423 | Nervous System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
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| Baseline |
| Cellular kinetics profile of MuSK-CAART | Cellular kinetics profile of MuSK-CAART after infusion. | Up to 36 months |
| Change in MuSK autoantibody titer | Change in MuSK autoantibody titer compared to pre-infusion visit by clinically validated assay. | Up to 36 months |
| Up to 36 months |
| Measurement of Clinical Symptoms using QMG | Measurement of clinical symptoms using the Quantitative Myasthenia Gravis (QMG) assessment. | Up to 36 months |
| Measurement of Clinical Symptoms using MGC | Measurement of clinical symptoms using the Myasthenia Gravis Composite (MGC) assessment. | Up to 36 months |
| Measurement of Quality of Life (QoL) using MG-QOL-15r | Measurement of Quality of Life using the MG-QOL-15r (Myasthenia Gravis Qualify of Life 15-item scale, revised) questionnaire. | Up to 36 months |
| Sacramento |
| California |
| 95817 |
| United States |
| University of Kansas Medical Center | Kansas City | Kansas | 66160 | United States |
| Oregon Health & Science University (OHSU) | Portland | Oregon | 97239 | United States |
| Houston Methodist Hospital | Houston | Texas | 77030 | United States |
| D010257 | Paraneoplastic Syndromes |
| D020274 | Autoimmune Diseases of the Nervous System |
| D009422 | Nervous System Diseases |
| D019636 | Neurodegenerative Diseases |
| D020511 | Neuromuscular Junction Diseases |
| D009135 | Muscular Diseases |
| D020879 | Neuromuscular Manifestations |
| D009461 | Neurologic Manifestations |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012816 | Signs and Symptoms |