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

Sponsor

Cabaletta Bio (Industry)

Overall Status

Recruiting

CT.gov ID

NCT06154252

Collaborator

(none)

Enrollment

Location

Arm

55.5

Anticipated Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Idiopathic Inflammatory Myopathy Dermatomyositis Anti-Synthetase Syndrome Immune-Mediated Necrotizing Myopathy	Biological: CAB-201 following preconditioning with fludarabine and cyclophosphamide	Phase 1/Phase 2

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), 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

18 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Nov 17, 2023

Anticipated Primary Completion Date :

Jul 1, 2028

Anticipated Study Completion Date :

Jul 1, 2028

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CABA-201 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 Single intravenous infusion of CABA-201 at a single dose level following preconditioning with fludarabine and cyclophosphamide

Arm

Intervention/Treatment

Experimental: CABA-201

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

Single intravenous infusion of CABA-201 at a single dose level following preconditioning with fludarabine and cyclophosphamide

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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 characterize the pharmacokinetics (PK) [Up to 156 weeks]
Levels of CABA-201-positive T 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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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