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 3RecruitingNCT06154252

Cabaletta Bio74 enrolled

Overview

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

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 Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Idiopathic Inflammatory Myopathy Dermatomyositis Anti-Synthetase Syndrome

Eligibility

Sex: ALLMin age: 6 YearsMax age: 75 Years

Medical Language ↔ Plain English

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.

Locations (31)

University of California Irvine - Accepting Adult Patients

Orange, California, United States

RECRUITING

University of California, San Francisco Benioff Children's Hospital - Accepting Young Adult and Juvenile Patients

San Francisco, California, United States

RECRUITING

Children's Hospital Colorado - Accepting Juvenile Patients

Aurora, Colorado, United States

NOT_YET_RECRUITING

Mayo Clinic Florida - Accepting Adult Patients

Jacksonville, Florida, United States

Outcomes

Primary Outcomes

Phase 1/2: Incidence and severity of adverse events (AEs)

Incidence and severity of AEs

Time frame: Up to 28 days after CABA-201 infusion

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

≥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

Time frame: Within 16 weeks

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

≥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

Time frame: Within 24 weeks

Secondary Outcomes

Incidence of adverse events and laboratory abnormalities

Incidence and severity of AEs, including changes in laboratory values and vital signs

Time frame: Up to 156 weeks (Phase 1/2) and through 52 weeks (Sub-study 1 and 2)

Pharmacodynamics (PD)

Levels of B cells in the blood

Time frame: Up to 156 weeks (Phase 1/2) and through 52 weeks (Sub-study 1 and 2)

Pharmacokinetics (PK)

Levels of CABA-201-positive T cells in the blood

Time frame: Up to 156 weeks (Phase 1/2) and through 52 weeks (Sub-study 1 and 2)

Change in disease-related biomarkers of muscle inflammation

Levels of muscle enzymes (CK, LDH, AST, ALT, and aldolase) in serum

Time frame: Up to 156 weeks (Phase 1/2)

Change in autoantibody-related biomarkers

Levels of autoantibodies from the Myositis-Specific Autoantibody Panel (e.g., MDA-5, Jo-1, and HMGCR) in the serum

Time frame: Up to 156 weeks (Phase 1/2)

Proportion of DM subjects achieving at least a moderate TIS without any immunomodulatory medications and no or low dose of steroids

≥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

Time frame: Week 16 (Sub-study 1)

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

MMT-8 measures muscle strength on a scale ranging from 0 to 150 points, where higher scores reflect greater muscle strength

Time frame: Week 16 (Sub-study 1)

Proportion of DM and ASyS subjects achieving a major TIS response without any immunomodulatory medications and no or low dose of steroids

≥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

Time frame: Week 16 (Sub-study 1)

Proportion of subjects with DM & ASyS achieving moderate TIS without any immunomodulatory medications on no or low dose of steroids

≥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

Time frame: Week 52 (Sub-study 1)

Proportion of subjects with DM achieving moderate TIS without any immunomodulatory medications on no or low dose of steroids

≥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

Time frame: Week 52 (Sub-study 1)

Mean change from baseline on the MMT-8 in subjects with IMNM without any immunomodulatory medications and no or low dose of steroids

MMT-8 measures muscle strength on a scale ranging from 0 to 150 points, where higher scores reflect greater muscle strength

Time frame: Week 24 (Sub-study 2)

Proportion of subjects with IMNM achieving at least minimal TIS response without immunomodulatory medications and no or low dose of steroids

≥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

Time frame: Week 52 (Sub-study 2)

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

Overview

Conditions

Interventions

Eligibility

Locations (31)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts