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
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Cabaletta Bio
- Enrollment
- 7
- Locations
- 5
- Primary Endpoint
- Adverse events
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
Arms & Interventions
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.
Intervention: MuSK-CAART (Biological)
Outcomes
Primary Outcomes
Adverse events
Time Frame: 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)
- Percent of CAAR-transduced cells(Baseline)
- Change in MuSK autoantibody titer(Up to 36 months)
- Cellular kinetics profile of MuSK-CAART(Up to 36 months)