Clinical trial NCT05451212: Open-label Study to Evaluate the Safety of Various Dosing Regimens of MuSK-CAART for MuSK Myasthenia Gravis
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
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
Lead sponsor: Cabaletta Bio
Sponsor class: INDUSTRY
First posted: 2022-07-11
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Adverse events
timeFrame: 3 months
Secondary outcomes:
measure: Total MuSK-CAART positive cells
timeFrame: Baseline
measure: Percent of CAAR-transduced cells
timeFrame: Baseline
measure: Cellular kinetics profile of MuSK-CAART
timeFrame: Up to 36 months
measure: Change in MuSK autoantibody titer
timeFrame: Up to 36 months
Other outcomes:
measure: Use of Concomitant Therapies
timeFrame: Up to 36 months
measure: Measurement of Clinical Symptoms using MG-ADL
timeFrame: Up to 36 months
measure: Measurement of Clinical Symptoms using QMG
timeFrame: Up to 36 months
measure: Measurement of Clinical Symptoms using MGC
timeFrame: Up to 36 months
measure: Measurement of Quality of Life (QoL) using MG-QOL-15r
timeFrame: Up to 36 months
Locations:
city: Orange
country: United States
facility: UC Irvine, Department of Neurology
state: California
city: Sacramento
country: United States
facility: UC Davis, Department of Neurology
state: California
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Portland
country: United States
facility: Oregon Health & Science University (OHSU)
state: Oregon
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
Study officials:
affiliation: Cabaletta Bio
name: Medical Director
role: STUDY_CHAIR
References: