Open-label Study to Determine the Maximum Tolerated Dose of MuSK-CAART for MuSK Myasthenia Gravis

• Sponsor: Cabaletta Bio (Industry)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT05451212
• Collaborator: (none)
• Enrollment: 24
• Arm: 1
• Anticipated Duration (Months): 70

Study Details

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 find the maximum tolerated dose 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. MuSK-CAART may potentially lead to complete and durable remission of disease.

Condition or Disease	Intervention/Treatment	Phase
MuSK Myasthenia Gravis	Biological: MuSK-CAART	Phase 1

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 24 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Anticipated Study Start Date: Dec 1, 2022
• Anticipated Primary Completion Date: Oct 1, 2028
• Anticipated Study Completion Date: Oct 1, 2028

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MuSK-CAART Cohort A: Infusion of MuSK-CAART at increasing dose levels (4 groups planned). Cohort B: Infusion of MuSK-CAART at the dose level selected from Part A.	Biological: MuSK-CAART; Intravenous infusion of MuSK-CAART at different doses

Outcome Measures

Primary Outcome Measures

1. 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

1. Total MuSK-CAART positive cells [Baseline]

   Total MuSK-CAART positive cells for each manufacturing run.

2. Percent of CAAR-transduced cells [Baseline]

   Percent of total cells for infusion that are CAAR (Chimeric Autoantibody Receptor)-transduced cells.

3. Cellular kinetics profile of MuSK-CAART [Up to 36 months]

   Cellular kinetics profile of MuSK-CAART after infusion.

4. Change in MuSK autoantibody titer [Up to 36 months]

   Change in MuSK autoantibody titer compared to pre-infusion visit by clinically validated assay.

Other Outcome Measures

1. Use of Concomitant Therapies [Up to 36 months]

   Frequency and dose of concomitant therapies.

2. Measurement of Clinical Symptoms using MG-ADL [Up to 36 months]

   Measurement of clinical symptoms using the Myasthenia Gravis Activities of Daily Living (MG-ADL) assessment.

3. Measurement of Clinical Symptoms using QMG [Up to 36 months]

   Measurement of clinical symptoms using the Quantitative Myasthenia Gravis (QMG) assessment.

4. Measurement of Clinical Symptoms using MGC [Up to 36 months]

   Measurement of clinical symptoms using the the Myasthenia Gravis Composite (MGC) assessment.

5. Measurement of Quality of Life (QoL) using MG-QOL-15r [Up to 36 months]

   Measurement of Quality of Life using the MG-QOL-15r (Myasthenia Gravis Qualify of Life 15-item scale, revised) questionnaire.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: 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 < 1,000/µL at screening.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Cabaletta Bio

Investigators

• Study Chair: Medical Director, Cabaletta Bio

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Cabaletta Bio
• ClinicalTrials.gov Identifier: NCT05451212
• Other Study ID Numbers: CAB-MuSK-101
• First Posted: Jul 11, 2022
• Last Update Posted: Jul 11, 2022
• Last Verified: Jul 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Cabaletta Bio: 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
• Additional relevant MeSH terms: Myasthenia Gravis; Muscle Weakness

Study Results

No Results Posted as of Jul 11, 2022