Back to resultsOpen-label Study to Evaluate the Safety of Various Dosing Regimens of MuSK-CAART for MuSK Myasthenia Gravis
Primary Purpose
MuSK Myasthenia Gravis
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
MuSK-CAART
Sponsored by
About this trial
This is an interventional treatment trial for MuSK Myasthenia Gravis focused on measuring 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
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 < 1,000/µL at screening.
Sites / Locations
- UC Irvine, Department of NeurologyRecruiting
- UC Davis, Department of NeurologyRecruiting
- University of Kansas Medical CenterRecruiting
- University of North Carolina at Chapel Hill
- Oregon Health & Science University (OHSU)Recruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
MuSK-CAART
Arm Description
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.
Outcomes
Primary Outcome Measures
Adverse events
Incidence of adverse events (AEs), including dose-limiting toxicities (DLTs) and AEs that are related to MuSK-CAART.
Secondary Outcome Measures
Total MuSK-CAART positive cells
Total MuSK-CAART positive cells for each manufacturing run.
Percent of CAAR-transduced cells
Percent of total cells for infusion that are CAAR (Chimeric Autoantibody Receptor)-transduced cells.
Cellular kinetics profile of MuSK-CAART
Cellular kinetics profile of MuSK-CAART after infusion.
Change in MuSK autoantibody titer
Change in MuSK autoantibody titer compared to pre-infusion visit by clinically validated assay.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05451212
Brief Title
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
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 23, 2022 (Actual)
Primary Completion Date
October 2028 (Anticipated)
Study Completion Date
October 2028 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cabaletta Bio
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
24 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
MuSK-CAART
Arm Type
Experimental
Arm Description
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 Type
Biological
Intervention Name(s)
MuSK-CAART
Intervention Description
Intravenous infusion of MuSK-CAART at different doses. Subjects may also receive MuSK-CAART following pre-treatment with CY, or CY plus FLU.
Primary Outcome Measure Information:
Title
Adverse events
Description
Incidence of adverse events (AEs), including dose-limiting toxicities (DLTs) and AEs that are related to MuSK-CAART.
Time Frame
3 months
Secondary Outcome Measure Information:
Title
Total MuSK-CAART positive cells
Description
Total MuSK-CAART positive cells for each manufacturing run.
Time Frame
Baseline
Title
Percent of CAAR-transduced cells
Description
Percent of total cells for infusion that are CAAR (Chimeric Autoantibody Receptor)-transduced cells.
Time Frame
Baseline
Title
Cellular kinetics profile of MuSK-CAART
Description
Cellular kinetics profile of MuSK-CAART after infusion.
Time Frame
Up to 36 months
Title
Change in MuSK autoantibody titer
Description
Change in MuSK autoantibody titer compared to pre-infusion visit by clinically validated assay.
Time Frame
Up to 36 months
Other Pre-specified Outcome Measures:
Title
Use of Concomitant Therapies
Description
Frequency and dose of concomitant therapies.
Time Frame
Up to 36 months
Title
Measurement of Clinical Symptoms using MG-ADL
Description
Measurement of clinical symptoms using the Myasthenia Gravis Activities of Daily Living (MG-ADL) assessment.
Time Frame
Up to 36 months
Title
Measurement of Clinical Symptoms using QMG
Description
Measurement of clinical symptoms using the Quantitative Myasthenia Gravis (QMG) assessment.
Time Frame
Up to 36 months
Title
Measurement of Clinical Symptoms using MGC
Description
Measurement of clinical symptoms using the Myasthenia Gravis Composite (MGC) assessment.
Time Frame
Up to 36 months
Title
Measurement of Quality of Life (QoL) using MG-QOL-15r
Description
Measurement of Quality of Life using the MG-QOL-15r (Myasthenia Gravis Qualify of Life 15-item scale, revised) questionnaire.
Time Frame
Up to 36 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Cabaletta Bio
Phone
+1 267 759 3100
Email
clinicaltrials@cabalettabio.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Cabaletta Bio
Official's Role
Study Chair
Facility Information:
Facility Name
UC Irvine, Department of Neurology
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mani Nistor
Phone
714-456-5956
Email
mnistor@hs.uci.edu
First Name & Middle Initial & Last Name & Degree
Ali Habib, MD
Facility Name
UC Davis, Department of Neurology
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joshua Valdez
Phone
916-734-7707
Email
joavaldez@ucdavis.edu
First Name & Middle Initial & Last Name & Degree
David Richman, MD
Facility Name
University of Kansas Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andrew J Heim
Phone
913-945-9926
Email
aheim2@kumc.edu
First Name & Middle Initial & Last Name & Degree
Mazen Dimachkie, MD
Facility Name
University of North Carolina at Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Oregon Health & Science University (OHSU)
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Katie Lewis
Phone
503-494-7394
Email
lewiskat@ohsu.edu
First Name & Middle Initial & Last Name & Degree
Nizar Chahin, MD
12. IPD Sharing Statement
Learn more about this trial
Open-label Study to Evaluate the Safety of Various Dosing Regimens of MuSK-CAART for MuSK Myasthenia Gravis
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