RESET-MG: A Study to Evaluate the Safety and Efficacy of CABA-201 in Participants With Generalized Myasthenia Gravis

RESET-MG: A Phase 1/2, Open-Label Study to Evaluate the Safety and Efficacy of Autologous CD19-specific Chimeric Antigen Receptor T Cells (CABA-201) in Participants With Generalized Myasthenia Gravis

RESET-MG: A Phase 1/2 Open-Label Study to Evaluate the Safety and Efficacy of CABA-201 in Participants with Generalized Myasthenia Gravis

Study Overview

• Status: Not yet recruiting
• Conditions: Generalized Myasthenia Gravis (gMG)
• Intervention / Treatment: Biological: CABA-201

Detailed Description

Myasthenia gravis (MG) is a rare autoimmune disorder characterized by autoantibody responses that cause defective transmission of signals at the neuromuscular junction, resulting in a distinctive pattern of weakness. Patients with generalized MG (gMG) typically experience symptoms associated with ocular disease in addition to weakness of many other voluntary muscle groups, including extremity, bulbar, and respiratory muscles. MG is considered a classic example of a B-cell mediated autoimmune disease. Currently, there are no curative treatments for MG. This study is being conducted to evaluate the safety and efficacy of an investigational cell therapy, CABA-201, that can be given to patients with gMG. A single dose of CABA-201 in combination with cyclophosphamide (CY) and fludarabine (FLU) will be evaluated.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Cabaletta Bio; Phone Number: +1 267 759 3100; Email: clinicaltrials@cabalettabio.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥18 and ≤70 years of age
• Diagnosis of MG with generalized muscle weakness meeting criteria as defined by the MGFA class II, III , IVa, and IVb.
• Diagnosis of seropositive (autoantibodies AChR, MuSK and/or LRP4) or seronegative MG

Exclusion Criteria:

• Contraindication to leukapheresis
• History of anaphylactic or severe systemic reaction to fludarabine, cyclophosphamide or any of their metabolites
• Active infection requiring medical intervention at screening
• Current symptoms of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, pulmonary, psychiatric, cardiac, neurological, or cerebral disease, including severe and uncontrolled infections, such as sepsis and opportunistic infections.
• Concomitant medical conditions that, in the opinion of the investigator, might place the subject at unacceptable risk for participation in this study, interfere with the assessment of the effects or safety of the investigational product or with the study procedures
• Significant lung or cardiac impairment
• Prior solid organ (heart, liver, kidney, lung) transplant or hematopoietic cell transplant

Other protocol-defined inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CABA-201; AChR Antibody-Positive Cohort AChR Antibody-Negative Cohort	Biological: CABA-201; Single intravenous infusion of CABA-201 at a single dose level following preconditioning with fludarabine and cyclophosphamide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate incidence and severity of adverse events (AEs)	An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal result of an investigation), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. The term AE is used to include both serious and non-serious AEs.	Up to 28 days after CABA-201 infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To characterize the pharmacodynamics (PD)	Levels of B cells in the blood	Up to 156 weeks
To characterize the pharmacokinetics (PK)	Levels of CABA-201-positive T cells in the blood	Up to 156 weeks
To evaluate the incidence and severity of adverse events (AEs)	An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal result of an investigation), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. The term AE is used to include both serious and non-serious AEs.	Up to 156 weeks
To evaluate disease-related biomarkers	Levels of MG-specific autoantibodies in the serum	Up to 156 weeks
To evaluate efficacy by change in Myasthenia Gravis - Activities of Daily Living (MG-ADL) score over time.	The MG-ADL scale is a validated instrument administered by a qualified assessor with 8 areas of activities of daily living as reported by patients: talking, chewing, swallowing, breathing, ability to brush teeth or comb hair, ability to rise from a chair, double vision, and eyelid droop. In each area, the score ranges from 0 (normal) to 3 (most severe). The total score is the sum of all subscores.	Up to 156 weeks
To evaluate efficacy by change in Quantitative Myasthenia Gravis (QMG) score over time.	The QMG score is a 13-item scale conducted by a qualified assessor to evaluate disease severity in patients with MG. The total score ranges from a minimum of 0 (no myasthenic findings) to 39 (maximum myasthenic deficits).	Up to 156 weeks
To evaluate efficacy by change in Myasthenia Gravis Composite (MGC) score over time.	The MGC scale is a physician-reported instrument for the assessment of MG patients' symptoms and impairments. It includes 10 domains, and the total score ranges from 0 (normal) to 50 (most severe).	Up to 156 weeks

Collaborators and Investigators

• Sponsor: Cabaletta Bio
• Investigators: Study Chair: Medical Director, Cabaletta Bio

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2024
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): September 1, 2029

Study Registration Dates

• First Submitted: March 21, 2024
• First Submitted That Met QC Criteria: April 5, 2024
• First Posted (Actual): April 11, 2024

Study Record Updates

• Last Update Posted (Actual): April 25, 2024
• Last Update Submitted That Met QC Criteria: April 24, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Myasthenia Gravis; cellular therapy; autoimmune disease; Neuromuscular; anti-CD19 CAR-T therapy; CABA-201; Anti-AChR; Anti-LRP4; Anti-MuSK
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Neoplasms; Autoimmune Diseases of the Nervous System; Autoimmune Diseases; Neoplasms by Site; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Neuromuscular Manifestations; Nervous System Neoplasms; Paraneoplastic Syndromes, Nervous System; Paraneoplastic Syndromes; Neuromuscular Junction Diseases; Muscle Weakness; Myasthenia Gravis
• Other Study ID Numbers: CAB-201-004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No