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

Sponsor

Cabaletta Bio (Industry)

Overall Status

Recruiting

CT.gov ID

NCT06121297

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Systemic Lupus Erythematosus Lupus Nephritis	Biological: CABA-201	Phase 1/Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

12 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

Single group assignment in two parallel cohortsSingle group assignment in two parallel cohorts

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Nov 1, 2023

Anticipated Primary Completion Date :

Dec 1, 2027

Anticipated Study Completion Date :

Dec 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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	Biological: CABA-201 Single intravenous infusion of CABA-201 at a single dose level following preconditioning with fludarabine and cyclophosphamide

Arm

Intervention/Treatment

Experimental: 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

Biological: CABA-201

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

Outcome Measures

Primary Outcome Measures

To evaluate incidence of adverse events [Up to 28 days after CABA-201 infusion]

Secondary Outcome Measures

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 disease related biomarkers [Up to 156 Weeks]
Levels of anti-double stranded DNA (anti-dsDNA) in serum
To evaluate efficacy [Up to 156 Weeks]
Complete renal response rates (in subjects with LN)
To evaluate efficacy [Up to 156 weeks]
SRI-4, BICLA and DORIS remission and LLDAS response rates

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.