RESET-SSc: An Open-Label Study to Evaluate the Safety and Efficacy of CABA-201, a CD19-CAR T Cell Therapy, in Subjects With Systemic Sclerosis

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 Systemic Sclerosis

RESET-SSc: A Phase 1/2 Open-Label Study to Evaluate the Safety and Efficacy of CABA-201, a CD19-CAR T cell therapy, in Subjects with Systemic Sclerosis

Study Overview

• Status: Not yet recruiting
• Conditions: Systemic Sclerosis; Scleroderma
• Intervention / Treatment: Biological: CABA-201

Detailed Description

Systemic sclerosis (SSc), also known as scleroderma , is a rare autoimmune disorder characterized by autoantibody production and abnormal B cell function. Though the cause of SSc is not well understood, it is thought to involve B cells that cause the body to attack different tissues in one's own body, causing skin and organ fibrosis. This study is being conducted to evaluate the safety and efficacy of an investigational therapy, CABA-201, a CD19-CAR T cell therapy, that can be given to patients with SSc who have active disease. A single dose of CABA-201 in combination with cyclophosphamide (CY) and fludarabine (FLU) will be evaluated.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Cabaletta Bio; Phone Number: +1 267 759 3100; Email: clinicaltrials@cabalettabio.com

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
      • Principal Investigator: Monalisa Ghosh, MD
      • Contact: James St. Clair; Phone Number: 734-936-5615; Email: ssc-coordinator@umich.edu
      • Contact: Neda Kortam; Phone Number: 734-763-4866; Email: ssc-coordinator@umich.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥18 and ≤70
• A clinical diagnosis of SSc, based on the 2013 American College of Rheumatology and European League Against Rheumatism classification criteria.
• Early active disease
• Evidence of significant skin, pulmonary, renal, or cardiac involvement

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 visit
• 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
• Severe lung or cardiac impairment
• Previous CAR T cell therapy
• Prior solid organ (heart, liver, kidney, lung) transplant or hematopoietic cell transplant

Other protocol-defined inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CABA-201; Severe Skin Cohort: Infusion of CABA-201 with preconditioning in subjects with SSc with severe skin involvement Organ Cohort: Infusion of CABA-201 with preconditioning in subjects with SSc with organ involvement	Biological: CABA-201; Single intravenous infusion of CABA-201 at a single dose level following preconditioning with fludarabine and cyclophosphamide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate incidence of adverse events	Incidence and severity of AEs	Up to 28 days after CABA-201 infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate adverse events and laboratory abnormalities	Incidence and severity of AEs, including changes in laboratory values and vital signs	Up to 156 weeks
To characterize the pharmacodynamics (PD)	Levels of B cells in the blood	Up to 156 weeks
To characterize the pharmacokinetics (PK)	Levels of CABA-201-positive T cells in the blood	Up to 156 weeks
To evaluate efficacy	Proportion of subjects achieving revised CRISS criteria	Up to 156 weeks

Collaborators and Investigators

• Sponsor: Cabaletta Bio
• Investigators: Study Director: Medical Director, Cabaletta Bio

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2024
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): July 1, 2029

Study Registration Dates

• First Submitted: March 19, 2024
• First Submitted That Met QC Criteria: March 19, 2024
• First Posted (Actual): March 25, 2024

Study Record Updates

• Last Update Posted (Actual): April 26, 2024
• Last Update Submitted That Met QC Criteria: April 25, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: systemic sclerosis; scleroderma; autoimmune disease; anti-CD19 CAR-T therapy; CABA-201
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Connective Tissue Diseases; Sclerosis; Scleroderma, Systemic; Scleroderma, Diffuse
• Other Study ID Numbers: CAB-201-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No