Anti-Synthetase Syndrome, Dermatomyositis, Idiopathic Inflammatory Myopathy, Immune-Mediated Necrotizing Myopathy, Juvenile Dermatomyositis, Juvenile Idiopathic Inflammatory Myopathy (JIIM), Juvenile Myositis, Juvenile Polymyositis
Conditions
Keywords
CABA-201, Autoimmune Disease, Anti-CD19 CAR-T therapy, Cellular Therapy, Idiopathic Inflammatory Myopathy, Myositis, Dermatomyositis, Anti-synthetase Syndrome, Immune-mediated Necrotizing Myopathy, Juvenile Dermatomyositis, Juvenile Polymyositis, Juvenile Idiopathic Inflammatory Myopathy (JIIM), Juvenile Myositis
Brief summary
RESET-Myositis: Open-Label Study to Evaluate the Safety and Efficacy of CABA-201 in Subjects with Active Idiopathic Inflammatory Myopathy or Juvenile Idiopathic Inflammatory Myopathy
Detailed description
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), immune-mediated necrotizing myopathy (IMNM), and juvenile idiopathic inflammatory myopathy (JIIM), 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, IMNM, or JIIM who have active disease. A single dose of CABA-201 in combination with cyclophosphamide (CY) and fludarabine (FLU) will be evaluated.
Interventions
BIOLOGICALCABA-201 following preconditioning with fludarabine and cyclophosphamide
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
6 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Adult Cohorts Inclusion Criteria: * Age ≥18 and ≤75 * A clinical diagnosis of IIM, based on the 2017 The European League Against Rheumatism/American College of Rheumatology classification criteria * Diagnosis of DM, ASyS, or IMNM * 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 Other protocol-defined criteria apply.
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 Other protocol-defined criteria apply. Juvenile Cohort Inclusion Criteria: * Age ≥6 and ≤17 years at enrollment * A clinical diagnosis of IIM, based on the 2017 The European League Against Rheumatism/American College of Rheumatology classification criteria * Evidence of active disease, despite prior or current treatment with standard of care treatments, as defined by the presence of elevated muscle enzymes, DM rash, or active disease on muscle biopsy, magnetic resonance imaging (MRI), or electromyography Other protocol-defined criteria apply.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1/2: Incidence and severity of adverse events (AEs) | Up to 28 days after CABA-201 infusion | Incidence and severity of AEs |
| Phase 2b Sub-study 1: Proportion of DM & ASyS subjects achieving at least a moderate Total Improvement Score (TIS) without any immunomodulatory medications and no or low dose of steroids | Within 16 weeks | ≥40 on the TIS, a composite measure ranging from 0 to 100, derived from six Core Set Measures, with higher scores indicating greater clinical improvement |
| Phase 2b Sub-study 2: Proportion of subjects with IMNM achieving at least a minimal TIS without any immunomodulatory medications and no or low dose of steroids | Within 24 weeks | ≥20 on the TIS, a composite measure ranging from 0 to 100, derived from six Core Set Measures, with higher scores indicating greater clinical improvement |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of adverse events and laboratory abnormalities | Up to 156 weeks (Phase 1/2) and through 52 weeks (Sub-study 1 and 2) | Incidence and severity of AEs, including changes in laboratory values and vital signs |
| Pharmacodynamics (PD) | Up to 156 weeks (Phase 1/2) and through 52 weeks (Sub-study 1 and 2) | Levels of B cells in the blood |
| Pharmacokinetics (PK) | Up to 156 weeks (Phase 1/2) and through 52 weeks (Sub-study 1 and 2) | Levels of CABA-201-positive T cells in the blood |
| Change in disease-related biomarkers of muscle inflammation | Up to 156 weeks (Phase 1/2) | Levels of muscle enzymes (CK, LDH, AST, ALT, and aldolase) in serum |
| Change in autoantibody-related biomarkers | Up to 156 weeks (Phase 1/2) | Levels of autoantibodies from the Myositis-Specific Autoantibody Panel (e.g., MDA-5, Jo-1, and HMGCR) in the serum |
| Proportion of DM subjects achieving at least a moderate TIS without any immunomodulatory medications and no or low dose of steroids | Week 16 (Sub-study 1) | ≥40 on the TIS, a composite measure ranging from 0 to 100, derived from six Core Set Measures, with higher scores indicating greater clinical improvement |
| Mean change from baseline on the MMT-8 in subjects with DM and ASyS without any immunomodulatory medications and no or low dose of steroids | Week 16 (Sub-study 1) | MMT-8 measures muscle strength on a scale ranging from 0 to 150 points, where higher scores reflect greater muscle strength |
| Proportion of DM and ASyS subjects achieving a major TIS response without any immunomodulatory medications and no or low dose of steroids | Week 16 (Sub-study 1) | ≥60 on the TIS, a composite measure ranging from 0 to 100, derived from six Core Set Measures, with higher scores indicating greater clinical improvement |
| Proportion of subjects with DM & ASyS achieving moderate TIS without any immunomodulatory medications on no or low dose of steroids | Week 52 (Sub-study 1) | ≥40 on the TIS, a composite measure ranging from 0 to 100, derived from six Core Set Measures, with higher scores indicating greater clinical improvement |
| Proportion of subjects with DM achieving moderate TIS without any immunomodulatory medications on no or low dose of steroids | Week 52 (Sub-study 1) | ≥40 on the TIS, a composite measure ranging from 0 to 100, derived from six Core Set Measures, with higher scores indicating greater clinical improvement |
| Mean change from baseline on the MMT-8 in subjects with IMNM without any immunomodulatory medications and no or low dose of steroids | Week 24 (Sub-study 2) | MMT-8 measures muscle strength on a scale ranging from 0 to 150 points, where higher scores reflect greater muscle strength |
| Proportion of subjects with IMNM achieving at least minimal TIS response without immunomodulatory medications and no or low dose of steroids | Week 52 (Sub-study 2) | ≥20 on the TIS, a composite measure ranging from 0 to 100, derived from six Core Set Measures, with higher scores indicating greater clinical improvement |
Countries
United Kingdom, United States
Contacts
CONTACTCabaletta Bio
STUDY_CHAIRMedical Director
Cabaletta Bio
Outcome results
None listed