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

Phase 1

Recruiting

• Conditions: MuSK Myasthenia Gravis
• Interventions: Biological: MuSK-CAART

• Registration Number: NCT05451212
• Lead Sponsor: Cabaletta Bio

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-06-30
• Study First Submitted QC: 2022-07-05
• Study First Posted: 2022-07-11
• Study Start: 2022-11-23
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-25
• Last Update Posted: 2024-10-29
• Primary Completion: 2028-10
• Study Completion: 2028-10

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 24

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
MuSK-CAART	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.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
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.
Change in MuSK autoantibody titer	Up to 36 months	Change in MuSK autoantibody titer compared to pre-infusion visit by clinically validated assay.
Cellular kinetics profile of MuSK-CAART	Up to 36 months	Cellular kinetics profile of MuSK-CAART after infusion.

Trial Locations

Locations (5)

Houston Methodist Hospital; 🇺🇸 Houston, Texas, United States

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