Open-label Study to Evaluate the Safety of Various Dosing Regimens of MuSK-CAART for MuSK Myasthenia Gravis

NCT05451212 — Phase 1, Completed, 7 participants, Cabaletta Bio

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A Phase 1, Open-label, Safety and Dose-finding Study of Autologous Muscle-specific Tyrosine Kinase Chimeric Autoantibody Receptor T Cells (MuSK-CAART) in Subjects With Anti-MuSK-antibody-positive Myasthenia Gravis

Registry	NCT05451212
Status	Completed
Phase	Phase 1
Study type	Interventional; na, single group, masking: none, treatment
Enrollment	7 (Actual)
Sponsor	Cabaletta Bio (Industry)
Conditions	MuSK Myasthenia Gravis
Interventions	MuSK-CAART (Biological)
Dates	start 2022-11-23, primary completion 2025-07-24, completion 2025-07-24, first posted 2022-07-11, last updated 2025-11-10
Locations	5 sites in United States

-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.

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+Arms and interventions

Arm	Type	Interventions	Description
MuSK-CAART	Experimental	Biological: MuSK-CAART	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.

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.

+Outcome measures

Primary outcomes

Adverse events [3 months]: Incidence of adverse events (AEs), including dose-limiting toxicities (DLTs) and AEs that are related to MuSK-CAART.

Secondary outcomes

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 outcomes

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.

+Eligibility

Sex: All, ages: 18 Years to any

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.

+Locations (5)

Facility	City	Country
UC Irvine, Department of Neurology	Orange, California	United States
UC Davis, Department of Neurology	Sacramento, California	United States
University of Kansas Medical Center	Kansas City, Kansas	United States
Oregon Health & Science University (OHSU)	Portland, Oregon	United States
Houston Methodist Hospital	Houston, Texas	United States

+Investigators

Medical Director, Study chair, Cabaletta Bio