Lupus Nephritis, Systemic Lupus Erythematosus
Conditions
Keywords
CABA-201, Autoimmune Disease, Anti-CD19 CAR-T therapy, Cellular Therapy, Systemic Lupus Erythematosus, Lupus Nephritis
Brief summary
RESET-SLE: A Phase 1/2 Open-Label Study to Evaluate the Safety and Efficacy of CABA-201 in Subjects With Active Systemic Lupus Erythematosus
Detailed description
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, also called resecabtagene autoleucel, or "rese-cel". Rese-cel can be given to patients with either LN or SLE without renal involvement, in two separate parallel cohorts, who have active disease. Initially a single dose of CABA-201 in patients pretreated with a standard regimen including cyclophosphamide (CY) and fludarabine (FLU), will be evaluated. In addition, escalating doses of CABA-201 will be evaluated in patients without CY and FLU pretreatment.
Interventions
BIOLOGICALCABA-201
Single intravenous infusion of CABA-201 at a single dose level following preconditioning with fludarabine and cyclophosphamide
Sponsors
Cabaletta Bio
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To evaluate incidence of adverse events | Up to 28 days after CABA-201 infusion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate adverse events and laboratory abnormalities | Up to 156 weeks | Incidence and severity of AEs, including changes in laboratory values and vital signs |
| To characterize the pharmacodynamics (PD) | Up to 156 weeks | Levels of B cells in the blood |
| To characterize the pharmacokinetics (PK) | Up to 156 weeks | Levels of CABA-201-positive T cells in the blood |
| To evaluate disease related biomarkers | Up to 156 weeks | Levels of C3, C4, and CH50 in serum |
| To evaluate efficacy | Up to 156 Weeks | Complete renal response rates (in subjects with LN) |
Countries
Canada, Spain, United States
Contacts
CONTACTCabaletta Bio
STUDY_CHAIRMedical Director
Cabaletta Bio
Outcome results
None listed