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

Systemic Lupus Erythematosus Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06121297
• Other study ID #: CAB-201-001
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: February 16, 2024
• Est. completion date: December 2027

Study information

• Verified date: May 2024
• Source: Cabaletta Bio
• Contact: Cabaletta Bio
• Phone: +1 267 759 3100
• Email: clinicaltrials[@]cabalettabio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 12
• Est. completion date: December 2027
• Est. primary completion date: December 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Lupus Nephritis
• Nephritis
• Systemic Lupus Erythematosus

Intervention

Biological:
• CABA-201
Single intravenous infusion of CABA-201 at a single dose level following preconditioning with fludarabine and cyclophosphamide

Locations

Country	Name	City	State
United States	Emory University	Atlanta	Georgia
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	UNC Chapel Hill	Chapel Hill	North Carolina
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	University of Minnesota	Minneapolis	Minnesota
United States	Columbia University Irving Medical Center	New York	New York
United States	University of California Irvine	Orange	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	University of Rochester	Rochester	New York
United States	UC Davis Health	Sacramento	California
United States	UMass Memorial Hospital	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Cabaletta Bio

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To evaluate incidence of adverse events		Up to 28 days after CABA-201 infusion
Secondary	To evaluate adverse events and laboratory abnormalities	Incidence and severity of AEs, including changes in laboratory values and vital signs	Up to 156 weeks
Secondary	To characterize the pharmacodynamics (PD)	Levels of B cells in the blood	Up to 156 weeks
Secondary	To characterize the pharmacokinetics (PK)	Levels of CABA-201-positive T cells in the blood	Up to 156 weeks
Secondary	To evaluate disease related biomarkers	Levels of C3, C4, and CH50 in serum	Up to 156 weeks
Secondary	To evaluate disease related biomarkers	Levels of anti-double stranded DNA (anti-dsDNA) in serum	Up to 156 Weeks
Secondary	To evaluate efficacy	Complete renal response rates (in subjects with LN)	Up to 156 Weeks
Secondary	To evaluate efficacy	SRI-4, BICLA and DORIS remission and LLDAS response rates	Up to 156 weeks