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

Phase 1

Recruiting

• Conditions: Generalized Myasthenia Gravis (gMG)
• Interventions: Biological: CABA-201

• Registration Number: NCT06359041
• Lead Sponsor: Cabaletta Bio

Brief Summary

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

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 Timeline

• Study First Submitted: 2024-03-21
• Study First Submitted QC: 2024-04-05
• Study First Posted: 2024-04-11
• Status Verified: 2024-12
• Study Start: 2024-12
• Last Update Submitted: 2024-12-09
• Last Update Posted: 2024-12-11
• Primary Completion: 2029-09
• Study Completion: 2029-09

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 12

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CABA-201	CABA-201	AChR Antibody-Positive Cohort AChR Antibody-Negative Cohort

Primary Outcome Measures

Name	Time	Method
To evaluate incidence and severity of adverse events (AEs)	Up to 28 days after CABA-201 infusion	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.

Secondary Outcome Measures

Name	Time	Method
To evaluate efficacy by change in Myasthenia Gravis - Activities of Daily Living (MG-ADL) score over time.	Up to 156 weeks	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.
To evaluate efficacy by change in Quantitative Myasthenia Gravis (QMG) score over time.	Up to 156 weeks	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).
To evaluate efficacy by change in Myasthenia Gravis Composite (MGC) score over time.	Up to 156 weeks	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).
To evaluate disease-related biomarkers	Up to 156 weeks	Levels of MG-specific autoantibodies in the serum
To evaluate the incidence and severity of adverse events (AEs)	Up to 156 weeks	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.
To characterize the pharmacodynamics (PD)	Up to 156 weeks	Levels of B cells in the blood
To characterize the pharmacokinetics (PK)	Up to 156 weeks	Levels of CABA-201-positive T cells in the blood

Trial Locations

Locations (4)

Columbia University; 🇺🇸 New York, New York, United States

University of California Irvine; 🇺🇸 Orange, California, United States

UC Davis, Department of Neurology; 🇺🇸 Sacramento, California, United States

Houston Methodist Hospital; 🇺🇸 Houston, Texas, United States