Generalized Myasthenia Gravis (gMG)
Conditions
Keywords
CABA-201, autoimmune disease, anti-CD19 CAR-T therapy, cellular therapy, Myasthenia Gravis, Neuromuscular, Anti-AChR, Anti-LRP4, Anti-MuSK
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. In addition, escalating doses of CABA-201 will be evaluated in patients without CY and FLU preconditioning.
Interventions
BIOLOGICALCABA-201
Single intravenous infusion of CABA-201 at a single dose level following preconditioning with fludarabine and cyclophosphamide
Sponsors
Cabaletta Bio
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| To evaluate disease-related biomarkers | Up to 156 weeks | Levels of MG-specific autoantibodies in the serum |
| 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). |
Countries
United States
Contacts
CONTACTCabaletta Bio
STUDY_CHAIRMedical Director
Cabaletta Bio
Outcome results
None listed