Open-Label Study to Evaluate the Safety and Efficacy of CABA-201 in Subjects With Active Idiopathic Inflammatory Myopathy

Study Overview
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Brief Summary
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Open-Label Study to Evaluate the Safety and Efficacy of CABA-201 in Subjects with Active Idiopathic Inflammatory Myopathy

Detailed Description
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Idiopathic inflammatory myopathies (IIMs, or myositis) are a group of rare autoimmune diseases characterized by inflammation and muscle weakness. Though the cause of IIM is not well understood, some subtypes of IIM, including dermatomyositis (DM), anti-synthetase syndrome (ASyS), and immune-mediated necrotizing myopathy (IMNM), are thought to involve B cells that cause the body to attack different tissues in the body. 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 DM, ASyS, and IMNM who have active disease. A single dose of CABA-201 in combination with cyclophosphamide (CY) and fludarabine (FLU) will be evaluated.

Official Title
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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 Subjects With Active Idiopathic Inflammatory Myopathy

Conditions
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Idiopathic Inflammatory Myopathy, Dermatomyositis, Anti-Synthetase Syndrome, Immune-Mediated Necrotizing Myopathy

Intervention / Treatment
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* Biological: CAB-201 following preconditioning with fludarabine and cyclophosphamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 and ≤65 A clinical diagnosis of IIM, based on the 2017 The European League Against Rheumatism/American College of Rheumatology classification criteria Diagnosis of DM, ASyS, IMNM based on the presence of serum myositis-specific antibodies Evidence of active disease, despite prior or current treatment with standard of care treatments, as defined by the presence of elevated creatine kinase (CK), DM rash, or active disease on muscle biopsy, magnetic resonance imaging (MRI), or electromyography Presence of muscle weakness 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 Previous CAR T cell therapy Prior solid organ (heart, liver, kidney, lung) transplant or hematopoietic cell transplant

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CABA-201<br>DM Cohort: Infusion of CABA-201 following preconditioning with fludarabine and cyclophosphamide preconditioning in subjects with DM ASyS Cohort: Infusion of CABA-201 following preconditioning with fludarabine and cyclophosphamide preconditioning in subjects with ASyS IMNM Cohort: Infusion of CABA-201 following preconditioning with fludarabine and cyclophosphamide preconditioning in subjects with IMNM | Biological: CAB-201 following preconditioning with fludarabine and cyclophosphamide<br>* Single intravenous infusion of CABA-201 at a single dose level following preconditioning with fludarabine and cyclophosphamide<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate adverse events reported by subjects | Incidence and severity of AEs | Up to 28 days after CABA-201 infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate adverse events and laboratory abnormalities | Incidence and severity of AEs, including changes in laboratory values and vital signs | Up to 156 weeks | 
| 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 disease-related biomarkers of muscle inflammation | Levels of muscle enzymes (CK, LDH, AST, ALT, and aldolase) in serum | Up to 156 weeks | 
| To evaluate autoantibody -related biomarkers | Levels of autoantibodies from the Myositis-Specific Autoantibody Panel (e.g., MDA-5, Jo-1, and HMGCR) in the serum | Up to 156 Weeks | 
| To evaluate efficacy | Total Improvement Score (0 to 100, with higher scores indicating greater improvement) based on the Core Set Measures | Up to 156 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Myositis, CABA-201, Autoimmune Disease, Anti-CD19 CAR-T therapy, Cellular Therapy, Idiopathic Inflammatory Myopathy, Dermatomyositis, Anti-synthetase Syndrome, Immune-mediated Necrotizing Myopathy