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.

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.

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).