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

Phase 1

Recruiting

• Conditions: Systemic Lupus Erythematosus; Lupus Nephritis
• Interventions: Biological: CABA-201

• Registration Number: NCT06121297
• Lead Sponsor: Cabaletta Bio

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.

Study Timeline

• Study First Submitted: 2023-10-23
• Study First Submitted QC: 2023-11-01
• Study First Posted: 2023-11-07
• Study Start: 2024-02-16
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-19
• Last Update Posted: 2024-12-20
• Primary Completion: 2027-12
• Study Completion: 2027-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 12

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CABA-201	CABA-201	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

Primary Outcome Measures

Name	Time	Method
To evaluate incidence of adverse events	Up to 28 days after CABA-201 infusion

Secondary Outcome Measures

Name	Time	Method
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 evaluate disease related biomarkers	Up to 156 Weeks	Levels of anti-double stranded DNA (anti-dsDNA) in serum
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 efficacy	Up to 156 weeks	SRI-4, BICLA and DORIS remission and LLDAS response rates

Trial Locations

Locations (19)

Clinica Universitaria de Navarra; 🇪🇸 Pamplona, Navarra, Spain

UC Davis Health; 🇺🇸 Sacramento, California, United States

University of California Irvine; 🇺🇸 Orange, California, United States

Yale University; 🇺🇸 New Haven, Connecticut, United States

University of Florida Health; 🇺🇸 Gainesville, Florida, United States

Mayo Clinic; 🇺🇸 Jacksonville, Florida, United States

Emory University; 🇺🇸 Atlanta, Georgia, United States

Northwestern Memorial Hospital; 🇺🇸 Chicago, Illinois, United States

The University of Chicago Medical Center; 🇺🇸 Chicago, Illinois, United States

University of Kansas Medical Center; 🇺🇸 Kansas City, Kansas, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Brigham and Women's Hospital; 🇺🇸 Boston, Massachusetts, United States

UMass Memorial Hospital; 🇺🇸 Worcester, Massachusetts, United States

University of Minnesota; 🇺🇸 Minneapolis, Minnesota, United States

Columbia University Irving Medical Center; 🇺🇸 New York, New York, United States

University of Rochester; 🇺🇸 Rochester, New York, United States

UNC Chapel Hill; 🇺🇸 Chapel Hill, North Carolina, United States

Children's Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States

University of Texas MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States