This is an open-label, dose escalation study in patients with relapsed and refractory autoimmune diseases. Study drug, TI-0032-III injection, is composed of lipid nanoparticles (LNPs) targeting T cells that encapsulate circular RNA encoding the CD19 chimeric antigen receptor (CAR), which is a therapeutic biological product. It is clinically intended for the treatment of various relapsed and refractory B cell-related autoimmune diseases, such as systemic lupus erythematosus, sjögren's syndrome, systemic sclerosis, idiopathic inflammatory myositis, and antiphospholipid syndrome.
Understand trial procedures and methods, voluntarily sign the informed consent form .
Age ranges from 18 to 65 years old (including threshold), regardless of gender.
Positive expression of CD19 on peripheral blood B cells determined by flow cytometry.
Bone marrow function: neutrophil count ≥ 1.5 × 10^9/L, lymphocyte count ≥ 0.8 × 10^9/L, hemoglobin ≥ 90 g/L, platelet ≥ 100 × 10^9/L. Blood transfusion and growth factors must not be used within 14 days prior to screening to meet the above requirements.
Any RNA-LNP products or other LNP drugs received within the past two years.
Received intravenous gamma immunoglobulin within 24 weeks prior to screening.
Received plasmapheresis therapy within 12 weeks prior to screening.
Subjects who have not fully recovered from surgery within 4 weeks prior to screening.
Single group
TI-0032-III injection
Biological/VaccineMultiple doses of TI-0032-III injection will be infused
Safety outcomes
Safety assessments are conducted using the NCI-CTCAE version 5.0 standards
Efficacy outcome for systemic lupus erythematosus
Systemic lupus erythematosus-SLE Responder Index-4 (SRI-4) response expressing in percentages
Efficacy outcome for Sjögren's syndrome
Sjögren's syndrome -Sjögren's Tool for Assessing Response (STAR) presented as accumulated scores
Efficacy outcome for systemic sclerosis
Systemic sclerosis-Composite Response Index in Systemic Sclerosis (CRISS) score
Efficacy outcome for inflammatory myopathy
Inflammatory myopathy-Total Improvement Score (TIS)
Exploratory PK outcomes
Rate of CAR expression in peripheral blood cells
Exploratory PK outcomes
Quantification of circular RNA in peripheral blood
Exploratory PD outcome
Percentage and count of B cells in the peripheral blood
Exploratory PD outcome
Rate of B cell subsets (naïve B cells, memory B cells, transitional B cells, plasma cells and immature B cells) in the peripheral blood
