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

Phase 1

Not yet recruiting

• Conditions: Systemic Lupus Erythematosus (SLE); Systemic Sclerosis (SSc); Idiopathic Inflammatory Myopathy (IIM)

• Registration Number: NCT06913608
• Lead Sponsor: Calibr, a division of Scripps Research

Brief Summary

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.

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 Timeline

• Study First Submitted: 2025-03-28
• Status Verified: 2025-04
• Study First Submitted QC: 2025-04-03
• Last Update Submitted: 2025-04-03
• Study First Posted: 2025-04-06
• Last Update Posted: 2025-04-06
• Study Start: 2025-05
• Primary Completion: 2028-08
• Study Completion: 2028-08

Recruitment & Eligibility

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

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Number of subjects with adverse events	To 1 year post CLBR001 administration	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).

Secondary Outcome Measures

Name	Time	Method
Evaluate the pharmacokinetics (PK) of CLBR001 and SWI019: Area Under the Curve (AUC)	1 year post CLBR001 administration	Quantitation and persistence of CLBR001 cells in peripheral blood and PK parameters of SWI019
Evaluate the pharmacokinetics (PK) of CLBR001 and SWI019: Half-life (t1/2)	1 year post CLBR001 administration	Quantitation and persistence of CLBR001 cells in peripheral blood and PK parameters of SWI019
Evaluate the efficacy of CLBR001 + SWI019 in autoimmune disease	1 year post CLBR001 administration	Efficacy will be measured by the number of subjects with a clinical response.
Quantification of white blood cells (WBCs)	1 year post CLBR001 administration	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.
Evaluate the pharmacokinetics (PK) of CLBR001 and SWI019: Maximum Concentration (Cmax)	1 year post CLBR001 administration	Quantitation and persistence of CLBR001 cells in peripheral blood and PK parameters of SWI019
Number of subjects with Clinical Response	1 year post CLBR001 administration	Evaluate anti-disease activity of CLBR001 and SWI019 by number of subjects with Clinical Response to treatment.
Evaluate the pharmacokinetics (PK) of CLBR001 and SWI019: Time to Peak Drug Concentration (Tmax)	1 year post CLBR001 administration	Quantitation and persistence of CLBR001 cells in peripheral blood and PK parameters of SWI019
Assess immunogenicity of CLBR001 and SWI019	1 year post CLBR001 administration	Immunogenic response to CLBR001 and SWI019 will be measured by presence of antidrug antibodies (ADA).