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

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

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

Study Overview

• Status: Recruiting
• Conditions: Systemic Lupus Erythematosus; Lupus Nephritis
• Intervention / Treatment: Biological: CABA-201

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 Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Cabaletta Bio; Phone Number: +1 267 759 3100; Email: clinicaltrials@cabalettabio.com

Study Locations

• United States
  • California
    • Sacramento, California, United States, 95817
      • Recruiting
      • UC Davis Health
      • Principal Investigator: Gaurav Gulati, MD
      • Contact: Tammy Yotter; Phone Number: 916-734-6944; Email: tkyotter@ucdavis.edu
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
      • Principal Investigator: Meghan Sise, MD
      • Contact: Molly Bennett; Phone Number: 617-643-4395; Email: mgbennett@mgh.harvard.edu
    • Boston, Massachusetts, United States, 02115
      • Not yet recruiting
      • Brigham and Women's Hospital
      • Contact: Olivia Gabriel; Phone Number: 617-525-8250; Email: ogabriel@bwh.harvard.edu
      • Principal Investigator: Elena Massarotti, MD
  • Minnesota
    • Minneapolis, Minnesota, United States, 55414
      • Not yet recruiting
      • University of Minnesota
      • Contact: Patrick Nackman, MD; Phone Number: 612-624-9444; Email: pnachman@umn.edu
      • Principal Investigator: Patrick Nachman, MD, FASN
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Irving Medical Center
      • Principal Investigator: Anca Askanase, MD
      • Contact: Chloe Gong; Phone Number: 212-342-9051; Email: rg3271@cumc.columbia.edu
    • Rochester, New York, United States, 14642
      • Not yet recruiting
      • University of Rochester
      • Contact: Tyler Cavin; Phone Number: 585-273-2720; Email: Tyler_Cavin@URMC.Rochester.edu
      • Principal Investigator: Christopher Palma, MD, ScM
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Recruiting
      • UNC Chapel Hill
      • Contact: Shruti Saxena Beem; Phone Number: 919-966-0545; Email: shruti_saxena@med.unc.edu
      • Contact: Roger Huamani; Phone Number: 919-966-5688; Email: roger_huamani@med.unc.edu
      • Principal Investigator: Saira Sheikh, MD
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Children's Hospital of Philadelphia
      • Principal Investigator: Caitlin Elgarten
      • Contact: Anna Sparrow; Email: sparrowA@chop.edu
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • University of Texas MD Anderson Cancer Center
      • Principal Investigator: Biruh Workeneh, MD, FASN
      • Contact: Christine Griesmer; Phone Number: 832-846-0218; Email: clgriesmer@mdanderson.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To evaluate incidence of adverse events	Up to 28 days after CABA-201 infusion

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Cabaletta Bio
• Investigators: Study Chair: Medical Director, Cabaletta Bio

Study record dates

Study Major Dates

• Study Start (Actual): February 16, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: October 23, 2023
• First Submitted That Met QC Criteria: November 1, 2023
• First Posted (Actual): November 7, 2023

Study Record Updates

• Last Update Posted (Actual): April 1, 2024
• Last Update Submitted That Met QC Criteria: March 29, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Systemic Lupus Erythematosus; Autoimmune Disease; Lupus Nephritis; Cellular Therapy; CABA-201; Anti-CD19 CAR-T therapy
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Kidney Diseases; Urologic Diseases; Connective Tissue Diseases; Glomerulonephritis; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Lupus Erythematosus, Systemic; Nephritis; Lupus Nephritis
• Other Study ID Numbers: CAB-201-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No