A Study to Assess CLBR001+SWI019 in Subjects With Autoimmune Diseases

A Phase lb Open-Label Study Evaluating the Safety and Efficacy of the Combination of CLBR00l, an Engineered Autologous T Cell Product, and SWI019, a CD19-directed Antibody-based Biologic With or Without Lymphodepletion in Subjects With Autoimmune Disorders Including Systemic Lupus Erythematosus, Systemic Sclerosis, or Idiopathic Inflammatory Myositis

The goal of this clinical trial is to evaluate CLBR001 and SWI019 as a treatment for patients with autoimmune disorders, including systemic lupus erythematosus, systemic sclerosis, and idiopathic inflammatory myositis. Patients will be randomized 1:1 lymphodepletion vs no lymphodepletion arm. Patients will be administered a single infusion of CLBR001 cells followed by cycles of SWI019 with regular assessments of safety and disease response to treatment.

The goals are to establish the safety and efficacy of the combination therapy and determine if lymphodepletion is required for efficacy.

Study Overview

• Status: Withdrawn
• Conditions: Systemic Lupus Erythematosus (SLE); Systemic Sclerosis (SSc); Idiopathic Inflammatory Myopathy (IIM)
• Intervention / Treatment: Combination product: CLBR001 + SWI019

Detailed Description

CLBR001 + SWI019 is novel switchable CAR-T cell combination therapy comprised of an autologous CAR (chimeric antigen receptor)-T product (CLBR001, the switchable CAR-T cell [sCAR-T]) and SWI019 (the "switch" biologic molecule). SWI019 acts as an adapter molecule that controls the activity of the CLBR001 CAR-T cell product.

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Women or men age ≥18 of age at time of consent.
• Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of this study.
• Adequate hematological, liver, pulmonary, and cardiac function
• Willing to participate to participate in long term follow up study.
• Confirmed diagnosis of moderate to severe systemic lupus erythematosus with lupus nephritis, systemic lupus erythematosus with extrarenal lupus, systemic sclerosis, and idiopathic inflammatory myositis.
• Failed at least two immunosuppressive treatments

Exclusion Criteria:

• Inability to tolerate washout of prior therapy.
• Not willing/understanding the requirements of the clinical study
• Dependent on hemodialysis for a period of greater or equal to 3 months.
• Known hypersensitivity to prednisone or to both tocilizumab siltuximab.
• Have received plasmapheresis within 14 days prior to informed consent.
• Active bacterial, viral and/or fungal infection.
• Prior autologous/allogeneic stem cell transplant or solid organ transplant.
• Prior lentiviral or retroviral based therapy including CAR-T cell therapy.
• History or concurrent malignancy with active treatment in the past 5 years
• HIV-1 and HIV-2 antibody positive subjects.
• History of central nervous system diseases (such as seizure, psychosis, organic brain syndrome or cerebrovascular accident).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CLBR001 + SWI019 following Lymphodepletion; Subjects who are randomized into the lymphodepletion arm will undergo 3 days of lymphodepletion conditioning therapy consisting of fludarabine and cyclophosphamide prior to treatment with CLBR001+SWI019.	Combination product: CLBR001 + SWI019; Investigational switchable CAR-T cell therapy for autoimmune disorders
Experimental: CLBR001 + SWI019 without Lymphodepletion; Subjects who are randomized into the NO lymphodepletion arm will receive treatment with CLBR001+SWI019 without lymphodepletion administered prior.	Combination product: CLBR001 + SWI019; Investigational switchable CAR-T cell therapy for autoimmune disorders

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of subjects with adverse events	To assess the safety and tolerability in subjects by evaluating the frequency, relatedness, severity and duration of adverse events (assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0, with exception of Cytokine Release Syndrome (CRS) or Immune effector Cell-Associated Neurotoxicity Syndrome (ICANS) which will be graded by American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading criteria).	To 1 year post CLBR001 administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the efficacy of CLBR001 + SWI019 in autoimmune disease	Efficacy will be measured by the number of subjects with a clinical response.	1 year post CLBR001 administration
Quantification of white blood cells (WBCs)	Quantify WBCs, i.e. monocytes, neutrophils, other granulocytes, and lymphocytes, in peripheral blood to evaluate changes in circulating WBCs between subjects assigned to lymphodepletion vs no lymphodepletion arms to determine role of lymphodepletion in CAR-T cell engraftment.	1 year post CLBR001 administration
Evaluate the pharmacokinetics (PK) of CLBR001 and SWI019: Maximum Concentration (Cmax)	Quantitation and persistence of CLBR001 cells in peripheral blood and PK parameters of SWI019	1 year post CLBR001 administration
Assess immunogenicity of CLBR001 and SWI019	Immunogenic response to CLBR001 and SWI019 will be measured by presence of antidrug antibodies (ADA).	1 year post CLBR001 administration
Number of subjects with Clinical Response	Evaluate anti-disease activity of CLBR001 and SWI019 by number of subjects with Clinical Response to treatment.	1 year post CLBR001 administration
Evaluate the pharmacokinetics (PK) of CLBR001 and SWI019: Time to Peak Drug Concentration (Tmax)	Quantitation and persistence of CLBR001 cells in peripheral blood and PK parameters of SWI019	1 year post CLBR001 administration
Evaluate the pharmacokinetics (PK) of CLBR001 and SWI019: Area Under the Curve (AUC)	Quantitation and persistence of CLBR001 cells in peripheral blood and PK parameters of SWI019	1 year post CLBR001 administration
Evaluate the pharmacokinetics (PK) of CLBR001 and SWI019: Half-life (t1/2)	Quantitation and persistence of CLBR001 cells in peripheral blood and PK parameters of SWI019	1 year post CLBR001 administration

Collaborators and Investigators

• Sponsor: Calibr, a division of Scripps Research
• Investigators: Study Director: Calibr CMO, Calibr-Skaggs, Institute of Innovative Medicines

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2026
• Primary Completion (Actual): March 3, 2026
• Study Completion (Actual): March 3, 2026

Study Registration Dates

• First Submitted: March 28, 2025
• First Submitted That Met QC Criteria: April 3, 2025
• First Posted (Actual): April 6, 2025

Study Record Updates

• Last Update Posted (Actual): March 5, 2026
• Last Update Submitted That Met QC Criteria: March 3, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: CAR-T; systemic lupus erythematosus; SLE; cell therapy; systemic sclerosis; IIM; SSc; idiopathic inflammatory myopathy
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Nervous System Diseases; Muscular Diseases; Neuromuscular Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Lupus Erythematosus, Systemic; Scleroderma, Systemic; Myositis
• Other Study ID Numbers: CBR-sCAR19-3003

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
• product manufactured in and exported from the U.S.: No