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
Brief Title
RESET-Myositis: An 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.
Categories
Central Contacts
Central Contact Role
Contact
Central Contact Phone
267-759-3100
Central Contact Phone Ext
4444
Central Contact Email
clinicaltrials@cabalettabio.com
Completion Date
Completion Date Type
Estimated
Conditions
Idiopathic Inflammatory Myopathy
Dermatomyositis
Anti-Synthetase Syndrome
Immune-Mediated Necrotizing Myopathy
Juvenile Dermatomyositis
Juvenile Polymyositis
Juvenile Idiopathic Inflammatory Myopathy (JIIM)
Juvenile Myositis
Eligibility 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.
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.
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.
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.
Inclusion Criteria
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.
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.
* 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.
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.
Gender
All
Gender Based
false
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
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
75 Years
Minimum Age
6 Years
NCT Id
NCT06154252
Org Class
Industry
Org Full Name
Cabaletta Bio
Org Study Id
CAB-201-002
Overall Status
Recruiting
Phases
Phase 2
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
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 or Juvenile Idiopathic Inflammatory Myopathy
Primary Outcomes
Outcome Description
Incidence and severity of AEs
Outcome Measure
Phase 1/2: Incidence and severity of adverse events (AEs)
Outcome Time Frame
Up to 28 days after CABA-201 infusion
Outcome Description
≥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
Outcome Measure
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
Outcome Time Frame
Within 16 weeks
Outcome Description
≥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
Outcome Measure
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
Outcome Time Frame
Within 24 weeks
Secondary Outcomes
Outcome Description
Incidence and severity of AEs, including changes in laboratory values and vital signs
Outcome Time Frame
Up to 156 weeks (Phase 1/2) and through 52 weeks (Sub-study 1 and 2)
Outcome Measure
Incidence of adverse events and laboratory abnormalities
Outcome Description
Levels of B cells in the blood
Outcome Time Frame
Up to 156 weeks (Phase 1/2) and through 52 weeks (Sub-study 1 and 2)
Outcome Measure
Pharmacodynamics (PD)
Outcome Description
Levels of CABA-201-positive T cells in the blood
Outcome Time Frame
Up to 156 weeks (Phase 1/2) and through 52 weeks (Sub-study 1 and 2)
Outcome Measure
Pharmacokinetics (PK)
Outcome Description
Levels of muscle enzymes (CK, LDH, AST, ALT, and aldolase) in serum
Outcome Time Frame
Up to 156 weeks (Phase 1/2)
Outcome Measure
Change in disease-related biomarkers of muscle inflammation
Outcome Description
Levels of autoantibodies from the Myositis-Specific Autoantibody Panel (e.g., MDA-5, Jo-1, and HMGCR) in the serum
Outcome Time Frame
Up to 156 weeks (Phase 1/2)
Outcome Measure
Change in autoantibody-related biomarkers
Outcome Description
≥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
Outcome Time Frame
Week 16 (Sub-study 1)
Outcome Measure
Proportion of DM subjects achieving at least a moderate TIS without any immunomodulatory medications and no or low dose of steroids
Outcome Description
MMT-8 measures muscle strength on a scale ranging from 0 to 150 points, where higher scores reflect greater muscle strength
Outcome Time Frame
Week 16 (Sub-study 1)
Outcome Measure
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
Outcome Description
≥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
Outcome Time Frame
Week 16 (Sub-study 1)
Outcome Measure
Proportion of DM and ASyS subjects achieving a major TIS response without any immunomodulatory medications and no or low dose of steroids
Outcome Description
≥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
Outcome Time Frame
Week 52 (Sub-study 1)
Outcome Measure
Proportion of subjects with DM & ASyS achieving moderate TIS without any immunomodulatory medications on no or low dose of steroids
Outcome Description
≥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
Outcome Time Frame
Week 52 (Sub-study 1)
Outcome Measure
Proportion of subjects with DM achieving moderate TIS without any immunomodulatory medications on no or low dose of steroids
Outcome Description
MMT-8 measures muscle strength on a scale ranging from 0 to 150 points, where higher scores reflect greater muscle strength
Outcome Time Frame
Week 24 (Sub-study 2)
Outcome Measure
Mean change from baseline on the MMT-8 in subjects with IMNM without any immunomodulatory medications and no or low dose of steroids
Outcome Description
≥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
Outcome Time Frame
Week 52 (Sub-study 2)
Outcome Measure
Proportion of subjects with IMNM achieving at least minimal TIS response without immunomodulatory medications and no or low dose of steroids
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Child
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
75
Minimum Age Number (converted to Years and rounded down)
6
Investigators
Investigator Type
Principal Investigator
Investigator Name
Dawn Wahezi
Investigator Email
dwahezi@montefiore.org
Investigator Phone
718-696-2405
Investigator Department
Pediatrics
Investigator Division
Pediatric Rheumatology
Investigator Sponsor Organization
Montefiore
Study Department
Pediatrics
Study Division
Pediatrics Rheumatology
Categories Mesh Debug
Arthritis --- MUSCULOSKELETAL DISEASES
Child Development & Autism --- MUSCULOSKELETAL DISEASES
Orthopedics, Muscle & Bone --- MUSCULOSKELETAL DISEASES
Brain, Spinal Cord & Nervous System --- NEUROMUSCULAR DISEASES
Brain, Spinal Cord & Nervous System --- NERVOUS SYSTEM DISEASES
Brain, Spine & Nerve Cancers --- NERVOUS SYSTEM DISEASES
Infectious Disease --- IMMUNE SYSTEM DISEASES
Lung --- IMMUNE SYSTEM DISEASES
MeSH Terms
MYOSITIS
DERMATOMYOSITIS
AUTOIMMUNE DISEASES
MUSCULAR DISEASES
MUSCULOSKELETAL DISEASES
NEUROMUSCULAR DISEASES
NERVOUS SYSTEM DISEASES
POLYMYOSITIS
CONNECTIVE TISSUE DISEASES
SKIN AND CONNECTIVE TISSUE DISEASES
SKIN DISEASES
IMMUNE SYSTEM DISEASES
FLUDARABINE
CYCLOPHOSPHAMIDE
PHOSPHORAMIDE MUSTARDS
NITROGEN MUSTARD COMPOUNDS
MUSTARD COMPOUNDS
HYDROCARBONS, HALOGENATED
HYDROCARBONS
ORGANIC CHEMICALS
PHOSPHORAMIDES
ORGANOPHOSPHORUS COMPOUNDS