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

Dermatomyositis Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06154252
• Other study ID #: CAB-201-002
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: December 20, 2023
• Est. completion date: July 2028

Study information

• Verified date: April 2024
• Source: Cabaletta Bio
• Contact: Cabaletta Bio
• Phone: 12677593100
• Email: clinicaltrials[@]cabalettabio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 18
• Est. completion date: July 2028
• Est. primary completion date: July 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Dermatomyositis
• Idiopathic Inflammatory Myopathy
• Immune-Mediated Necrotizing Myopathy
• Muscular Diseases
• Myositis

Intervention

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

Locations

Country	Name	City	State
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	University of California Irvine	Orange	California
United States	Oregon Health & Science University	Portland	Oregon
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Cabaletta Bio

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To evaluate adverse events reported by subjects	Incidence and severity of AEs	Up to 28 days after CABA-201 infusion
Secondary	To evaluate adverse events and laboratory abnormalities	Incidence and severity of AEs, including changes in laboratory values and vital signs	Up to 156 weeks
Secondary	To characterize the pharmacodynamics (PD)	Levels of B cells in the blood	Up to 156 weeks
Secondary	To characterize the pharmacokinetics (PK)	Levels of CABA-201-positive T cells in the blood	Up to 156 weeks
Secondary	To evaluate disease-related biomarkers of muscle inflammation	Levels of muscle enzymes (CK, LDH, AST, ALT, and aldolase) in serum	Up to 156 weeks
Secondary	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
Secondary	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