Open-Label Study to Evaluate the Safety and Efficacy of CABA-201 in Subjects With Active Systemic Lupus Erythematosus

Study Overview
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Brief Summary
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Open-Label Study to Evaluate the Safety and Efficacy of CABA-201 in Subjects with Active Systemic Lupus Erythematosus

Detailed Description
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Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by autoantibody production and abnormal B cell function. SLE presents with fluctuating severity and may cause tissue damage in a variety of organs over time. Lupus nephritis (LN) (renal involvement) is a common severe manifestation of SLE, which can lead to significant morbidity and mortality. 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 either LN or SLE without renal involvement, in two separate parallel cohorts, who have active disease. A single dose of CABA-201 in patients who are pretreated with a standard regimen including cyclophosphamide (CY) and fludarabine (FLU) will be evaluated.

Official Title
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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 Systemic Lupus Erythematosus

Conditions
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Systemic Lupus Erythematosus, Lupus Nephritis

Intervention / Treatment
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* Biological: CABA-201


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 and ≤65 A clinical diagnosis of SLE, based on the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria for adult SLE. Positive antinuclear antibody (ANA) titer or anti-dsDNA antibody at screening. For LN subjects only, active, biopsy-proven LN class III or IV, with or without the presence of class V, according to 2018 Revised International Society of Nephrology/Renal Pathology Society (ISN/RPS) criteria For non-renal SLE subjects only: Active, moderate to severe SLE 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 For LN subjects only: The presence of kidney disease other than active lupus nephritis Previous CAR T cell therapy Prior solid organ (heart, liver, kidney, lung) transplant or hematopoietic cell transplant.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Single group assignment in two parallel cohorts
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CABA-201<br>LN Cohort: Infusion of CABA-201 with preconditioning in subjects with LN Non-renal SLE Cohort: Infusion of CABA-201 with preconditioning in subjects with SLE who do not meet criteria for inclusion in the LN cohort | Biological: CABA-201<br>* Single intravenous infusion of CABA-201 at a single dose level following preconditioning with fludarabine and cyclophosphamide<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate incidence of adverse events |  | 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 disease related biomarkers | Levels of C3, C4, and CH50 in serum | Up to 156 weeks | 
| To evaluate disease related biomarkers | Levels of anti-double stranded DNA (anti-dsDNA) in serum | Up to 156 Weeks | 
| To evaluate efficacy | Complete renal response rates (in subjects with LN) | Up to 156 Weeks | 
| To evaluate efficacy | SRI-4, BICLA and DORIS remission and LLDAS response rates | Up to 156 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CABA-201, Autoimmune Disease, Anti-CD19 CAR-T therapy, Cellular Therapy, Systemic Lupus Erythematosus, Lupus Nephritis