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

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

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.

Study Overview

• Status: Completed
• Conditions: MuSK Myasthenia Gravis
• Intervention / Treatment: Biological: MuSK-CAART

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Orange, California, United States, 92868
      • UC Irvine, Department of Neurology
    • Sacramento, California, United States, 95817
      • UC Davis, Department of Neurology
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University (OHSU)
  • Texas
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Biological: MuSK-CAART; Intravenous infusion of MuSK-CAART at different doses. Subjects may also receive MuSK-CAART following pre-treatment with CY, or CY plus FLU.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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.	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

Other Outcome Measures

Outcome Measure	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.	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

Collaborators and Investigators

• Sponsor: Cabaletta Bio
• Investigators: Study Chair: Medical Director, Cabaletta Bio

Study record dates

Study Major Dates

• Study Start (Actual): November 23, 2022
• Primary Completion (Actual): July 24, 2025
• Study Completion (Actual): July 24, 2025

Study Registration Dates

• First Submitted: June 30, 2022
• First Submitted That Met QC Criteria: July 5, 2022
• First Posted (Actual): July 11, 2022

Study Record Updates

• Last Update Posted (Estimated): November 10, 2025
• Last Update Submitted That Met QC Criteria: November 6, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Cell Therapy; Immune System Diseases; Autoimmunity; Musculoskeletal Diseases; Immunotherapy, Adoptive; Neuromuscular Diseases; Autoimmune Disease; Muscle Weakness; CAAR-T (Chimeric Autoantibody Receptor T Cells) Therapy; CAR-T (Chimeric Antigen Receptor T Cells) Therapy; Myasthenia Gravis (MG); Muscle-specific tyrosine kinase (MuSK)
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Muscular Diseases; Neuromuscular Manifestations; Pathologic Processes; Neoplasms by Site; Neoplasms; Autoimmune Diseases of the Nervous System; Neurodegenerative Diseases; Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Paraneoplastic Syndromes; Neuromuscular Junction Diseases; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Muscle Weakness; Myasthenia Gravis; Autoimmune Diseases; Musculoskeletal Diseases; Immune System Diseases; Neuromuscular Diseases
• Other Study ID Numbers: CAB-MuSK-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No