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

Phase 1

Recruiting

• Conditions: Idiopathic Inflammatory Myopathy; Dermatomyositis; Anti-Synthetase Syndrome; Immune-Mediated Necrotizing Myopathy; Juvenile Dermatomyositis; Juvenile Polymyositis; Juvenile Idiopathic Inflammatory Myopathy (JIIM); Juvenile Myositis
• Interventions: Biological: CABA-201 following preconditioning with fludarabine and cyclophosphamide

• Registration Number: NCT06154252
• Lead Sponsor: Cabaletta Bio

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.

Study Timeline

• Study First Submitted: 2023-11-16
• Study First Submitted QC: 2023-11-30
• Study First Posted: 2023-12-04
• Study Start: 2023-12-20
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-20
• Last Update Posted: 2024-12-27
• Primary Completion: 2028-07
• Study Completion: 2028-07

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 24

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, 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

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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

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
• Presence of serum myositis-specific antibodies or myositis-associated autoantibody
• 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

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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CABA-201	CABA-201 following preconditioning with fludarabine and cyclophosphamide	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. JIIM Cohort: Infusion of CABA-201 following preconditioning with fludarabine and cyclophosphamide preconditioning in subjects with JIIM.

Primary Outcome Measures

Name	Time	Method
To evaluate adverse events reported by subjects	Up to 28 days after CABA-201 infusion	Incidence and severity of AEs

Secondary Outcome Measures

Name	Time	Method
To characterize the pharmacokinetics (PK)	Up to 156 weeks	Levels of CABA-201-positive T cells in the blood
To evaluate adverse events and laboratory abnormalities	Up to 156 weeks	Incidence and severity of AEs, including changes in laboratory values and vital signs
To characterize the pharmacodynamics (PD)	Up to 156 weeks	Levels of B cells in the blood
To evaluate disease-related biomarkers of muscle inflammation	Up to 156 weeks	Levels of muscle enzymes (CK, LDH, AST, ALT, and aldolase) in serum
To evaluate autoantibody -related biomarkers	Up to 156 Weeks	Levels of autoantibodies from the Myositis-Specific Autoantibody Panel (e.g., MDA-5, Jo-1, and HMGCR) in the serum
To evaluate efficacy	Up to 156 Weeks	Total Improvement Score (0 to 100, with higher scores indicating greater improvement) based on the Core Set Measures

Trial Locations

Locations (11)

University of California Irvine - Accepting Adult Patients; 🇺🇸 Orange, California, United States

Mayo Clinic Florida - Accepting Adult Patients; 🇺🇸 Jacksonville, Florida, United States

Northwestern Memorial Hospital - Accepting Adult Patients; 🇺🇸 Chicago, Illinois, United States

The University of Chicago Medical Center - Accepting Adult and Juvenile Patients; 🇺🇸 Chicago, Illinois, United States

University of Kansas Medical Center - Accepting Adult Patients; 🇺🇸 Kansas City, Kansas, United States

Mayo Clinic - Accepting Adult Patients; 🇺🇸 Rochester, Minnesota, United States

Oregon Health & Science University - Accepting Adult Patients; 🇺🇸 Portland, Oregon, United States

Vanderbilt University Medical Center - Accepting Adult Patients; 🇺🇸 Nashville, Tennessee, United States

Houston Methodist Hospital - Accepting Adult Patients; 🇺🇸 Houston, Texas, United States

University of Texas MD Anderson Cancer Center - Accepting Adult Patients; 🇺🇸 Houston, Texas, United States

University College London Hospitals NHS Foundation Trust - Accepting Adult Patients; 🇬🇧 London, United Kingdom