Clinical trial NCT06359041: RESET-MG: A Study to Evaluate the Safety and Efficacy of CABA-201 in Participants With Generalized Myasthenia Gravis
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Generalized Myasthenia Gravis (gMG)
Keywords: CABA-201
autoimmune disease
anti-CD19 CAR-T therapy
cellular therapy
Myasthenia Gravis
Neuromuscular
Anti-AChR
Anti-LRP4
Anti-MuSK
Lead sponsor: Cabaletta Bio
Sponsor class: INDUSTRY
First posted: 2024-04-11
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: To evaluate incidence and severity of adverse events (AEs)
timeFrame: Up to 28 days after CABA-201 infusion
Secondary outcomes:
measure: To evaluate the incidence and severity of adverse events (AEs)
timeFrame: Up to 156 weeks
measure: To characterize the pharmacodynamics (PD)
timeFrame: Up to 156 weeks
measure: To characterize the pharmacokinetics (PK)
timeFrame: Up to 156 weeks
measure: To evaluate disease-related biomarkers
timeFrame: Up to 156 weeks
measure: To evaluate efficacy by change in Myasthenia Gravis - Activities of Daily Living (MG-ADL) score over time.
timeFrame: Up to 156 weeks
measure: To evaluate efficacy by change in Quantitative Myasthenia Gravis (QMG) score over time.
timeFrame: Up to 156 weeks
measure: To evaluate efficacy by change in Myasthenia Gravis Composite (MGC) score over time.
timeFrame: Up to 156 weeks
Other outcomes:
Locations:
city: Orange
country: United States
facility: University of California Irvine
state: California
city: Sacramento
country: United States
facility: UC Davis, Department of Neurology
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Jacksonville
country: United States
facility: Mayo Clinic Florida
state: Florida
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Worcester
country: United States
facility: University of Massachusetts Chan Medical School
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic - Rochester
state: Minnesota
city: New York
country: United States
facility: Columbia University
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Seattle
country: United States
facility: Swedish Neuroscience Research
state: Washington
Study officials:
affiliation: Cabaletta Bio
name: Medical Director
role: STUDY_CHAIR
References: