Clinical trial NCT06121297: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Systemic Lupus Erythematosus
Lupus Nephritis
Keywords: CABA-201
Autoimmune Disease
Anti-CD19 CAR-T therapy
Cellular Therapy
Systemic Lupus Erythematosus
Lupus Nephritis
Lead sponsor: Cabaletta Bio
Sponsor class: INDUSTRY
First posted: 2023-11-07
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single group assignment in two parallel cohorts
Primary purpose: TREATMENT

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, 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.

Eligibility criteria: 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.

Primary outcomes:
measure: To evaluate incidence of adverse events
timeFrame: Up to 28 days after CABA-201 infusion
Secondary outcomes:
measure: To evaluate adverse events and laboratory abnormalities
timeFrame: Up to 156 weeks
measure: To characterize the pharmacodynamics (PD)
timeFrame: Up to 156 weeks
measure: To characterize the pharmacokinetics (PK)
timeFrame: Up to 156 weeks
measure: To evaluate disease related biomarkers
timeFrame: Up to 156 weeks
measure: To evaluate disease related biomarkers
timeFrame: Up to 156 Weeks
measure: To evaluate efficacy
timeFrame: Up to 156 Weeks
measure: To evaluate efficacy
timeFrame: Up to 156 weeks
Other outcomes:
Locations:
city: Orange
country: United States
facility: University of California Irvine
state: California
city: Sacramento
country: United States
facility: UC Davis Health
state: California
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Gainesville
country: United States
facility: University of Florida Health
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Chicago
country: United States
facility: The University of Chicago Medical Center
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Worcester
country: United States
facility: UMass Memorial Hospital
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Chapel Hill
country: United States
facility: UNC Chapel Hill
state: North Carolina
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Pamplona
country: Spain
facility: Clinica Universitaria de Navarra
state: Navarra
Study officials:
affiliation: Cabaletta Bio
name: Medical Director
role: STUDY_CHAIR
References: