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

NCT05451212 | Completed Phase 1 FDA Drug

• 1 other identifier: CAB-MuSK-101
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 5

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.

Conditions

MuSK Myasthenia Gravis

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

Outcome Measures

Primary Outcomes (1)

• Adverse events

  Incidence of adverse events (AEs), including dose-limiting toxicities (DLTs) and AEs that are related to MuSK-CAART.

  3 months

Secondary Outcomes (4)

• Total MuSK-CAART positive cells

  Baseline

• Percent of CAAR-transduced cells

  Baseline

• Cellular kinetics profile of MuSK-CAART

  Up to 36 months

• Change in MuSK autoantibody titer

  Up to 36 months

Other Outcomes (5)

• Use of Concomitant Therapies

  Up to 36 months

• Measurement of Clinical Symptoms using MG-ADL

  Up to 36 months

• Measurement of Clinical Symptoms using QMG

  Up to 36 months

Study Arms (1)

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.

Biological: MuSK-CAART

Interventions

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.

MuSK-CAART

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Cabaletta Bio: lead

Study Sites (5)

UC Irvine, Department of Neurology

Orange, California, 92868, United States

Location

UC Davis, Department of Neurology

Sacramento, California, 95817, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Oregon Health & Science University (OHSU)

Portland, Oregon, 97239, United States

Location

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Myasthenia Gravis; Autoimmune Diseases; Immune System Diseases; Muscle Weakness; Neuromuscular Diseases; Musculoskeletal Diseases

Condition Hierarchy (Ancestors)

Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Paraneoplastic Syndromes; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Neurodegenerative Diseases; Neuromuscular Junction Diseases; Muscular Diseases; Neuromuscular Manifestations; Neurologic Manifestations; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms

Study Officials

• Medical Director

  Cabaletta Bio

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2022
• First Posted: July 11, 2022
• Study Start: November 23, 2022
• Primary Completion: July 24, 2025
• Study Completion: July 24, 2025
• Last Updated: November 10, 2025

Record last verified: 2025-11

Locations

US (5)