Clinical trial NCT06154252: 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
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Idiopathic Inflammatory Myopathy
Dermatomyositis
Anti-Synthetase Syndrome
Immune-Mediated Necrotizing Myopathy
Juvenile Dermatomyositis
Juvenile Polymyositis
Juvenile Idiopathic Inflammatory Myopathy (JIIM)
Juvenile Myositis
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
Lead sponsor: Cabaletta Bio
Sponsor class: INDUSTRY
First posted: 2023-12-04
Enrollment: 24
Sex: ALL
Minimum age (years): 6
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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, 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

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

Primary outcomes:
measure: To evaluate adverse events reported by subjects
timeFrame: Up to 28 days after CABA-201 infusion
Secondary outcomes:
measure: To evaluate adverse events and laboratory abnormalities
timeFrame: Up to 156 weeks
measure: To characterize the pharmacodynamics (PD)
timeFrame: Up to 156 weeks
measure: To characterize the pharmacokinetics (PK)
timeFrame: Up to 156 weeks
measure: To evaluate disease-related biomarkers of muscle inflammation
timeFrame: Up to 156 weeks
measure: To evaluate autoantibody -related biomarkers
timeFrame: Up to 156 Weeks
measure: To evaluate efficacy
timeFrame: Up to 156 Weeks
Other outcomes:
Locations:
city: Orange
country: United States
facility: University of California Irvine - Accepting Adult Patients
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco Benioff Children's Hospital - Accepting Young Adult and Juvenile Patients
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic Florida - Accepting Adult Patients
state: Florida
city: Atlanta
country: United States
facility: Emory University - Accepting Adult Patients
state: Georgia
city: Chicago
country: United States
facility: Northwestern Memorial Hospital - Accepting Adult Patients
state: Illinois
city: Chicago
country: United States
facility: The University of Chicago Medical Center - Accepting Adult and Juvenile Patients
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center - Accepting Adult Patients
state: Kansas
city: Rochester
country: United States
facility: Mayo Clinic - Accepting Adult Patients
state: Minnesota
city: Portland
country: United States
facility: Oregon Health & Science University - Accepting Adult Patients
state: Oregon
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia - Accepting Young Adult and Juvenile Patients
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center - Accepting Adult Patients
state: Tennessee
city: Houston
country: United States
facility: Houston Methodist Hospital - Accepting Adult Patients
state: Texas
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center - Accepting Adult Patients
state: Texas
city: London
country: United Kingdom
facility: Kings College Hospital NHS Foundation Trust - Accepting Adult Patients
city: London
country: United Kingdom
facility: University College London Hospitals NHS Foundation Trust - Accepting Adult Patients
city: Manchester
country: United Kingdom
facility: Manchester Royal Infirmary - Accepting Adult Patients
city: Salford
country: United Kingdom
facility: Salford Royal Hospital - Accepting Adult Patients
Study officials:
affiliation: Cabaletta Bio
name: Medical Director
role: STUDY_CHAIR
References: