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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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MuSK Myasthenia Gravis

Intervention / Treatment
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* Biological: MuSK-CAART


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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