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

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.

• CABA-201 (Biological), also known as Rese-cel, Resecabtagene autoleucel: Single intravenous infusion of CABA-201 at a single dose level following preconditioning with fludarabine and cyclophosphamide
• CABA-201 (Biological), also known as Rese-cel, Resecabtagene autoleucel: Single intravenous infusion of CABA-201 at a single dose level following preconditioning with fludarabine and cyclophosphamide

Primary outcomes

• Phase 1/2: To evaluate incidence of adverse events [Up to 28 days after CABA-201 infusion]: Incidence and severity of AEs
• Phase 2b Sub-study: To evaluate the efficacy of CABA-201 on % predicted forced vital capacity (FVC) in SSc-ILD subjects [Week 52]: Mean change from baseline in % predicted FVC without any immunomodulatory or anti-fibrotic medications and on no or low dose of steroids

Secondary outcomes

• To evaluate adverse events and laboratory abnormalities [Up to 156 weeks (Phase 1/2) and through 104 weeks (Sub-study)]: Incidence and severity of AEs, including changes in laboratory values and vital signs
• To characterize the pharmacodynamics (PD) [Up to 156 weeks (Phase 1/2) and through 104 weeks (Sub-study)]: Levels of B cells in the blood
• To characterize the pharmacokinetics (PK) [Up to 156 weeks (Phase 1/2) and through 104 weeks (Sub-study)]: Levels of CABA-201-positive T cells in the blood
• To evaluate efficacy [Up to 156 weeks (Phase 1/2) and at Week 52 (Sub-study)]: Proportion of subjects achieving revised Composite Response Index for Systemic Sclerosis (CRISS) criteria
• Mean change from baseline in Modified Rodnan Skin Score (mRSS) [Week 52 (Sub-study)]

Sex: All, ages: 18 Years to 75 Years

Inclusion Criteria:

* Age ≥18 and ≤75
* 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, 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.

• Medical Director, Study director, Cabaletta Bio