patients with refractory autoimmune diseases, such as Systemic Lupus Erythematosus (SLE) with neurological involvement, Systemic Sclerosis (SSc), ANCA-associated Vasculitis (AAV), Idiopathic Inflammatory Myopathies (IIM), Sjögren's Syndrome (SS), Multiple Sclerosis (MS), Neuromyelitis Optica Spectrum Disorders (NMOSD), Myasthenia Gravis (MG), Graves' disease, Autoimmune Encephalitis (AE), Autoimmune Hemolytic Anemia (AIHA), and Immune Thrombocytopenia (ITP).
Conditions
Interventions
Test group:The mRNA-LNP-delivered trispecific antibody will be administered as multiple infusions on days 0, 3, 7, and 14, with each infusion containing 2 mg
Sponsors
The First Affiliated Hospital of Guangzhou Medical University
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Inclusion criteria
Inclusion criteria: Enrolled cases must be selected according to the following criteria: Inclusion Criteria: Patients must meet all of the following inclusion criteria to be considered eligible for participation in this study. General Inclusion Criteria for All Patients: 1. The subject voluntarily participates in this trial and signs the informed consent form. 2. Age >= 18 years and = 1 × 10?/L, hemoglobin = 60 g/L, platelet count >= 20 × 10?/L, lymphocyte count > 0.3 × 10?/L. d) Coagulation function: International normalized ratio (INR) = 92% on room air at rest. f) Left ventricular ejection fraction (LVEF) >= 50% as shown by echocardiography. 4.Female subjects of childbearing potential must have a negative serum or urine pregnancy test at screening. 5.Patients who have failed to respond to conventional drug therapy or who have experienced severe side effects from conventional drug therapy. Inclusion Criteria for Patients with SLE: 1. Diagnosis of SLE according to the 2019 EULAR/ACR classification criteria or the 2012 SLICC criteria. 2. Must have received treatment with glucocorticoids combined with immunosuppressants and/or biologics for at least 2 months prior to screening, with a stable dose for > 2 weeks, and the disease is still active (i.e., prior treatment with glucocorticoids + immunosuppressants or glucocorticoids + immunosuppressants + biologics; monotherapy with any of these agents does not qualify). Oral corticosteroids must meet the following requirements: 1) Prednisone (or equivalent) >= 7.5 mg/day; 2) When used in combination with immunosuppressants and/or biologics, there is no daily minimum dose requirement for corticosteroids. 3. Positive for antinuclear antibody (ANA), and/or positive for anti-dsDNA antibody, and/or positive for anti-Smith antibody at screening. 4. SEDAI-2K score > 6 and "clinical" SLEDAI-2K score >= 4 at screening. Note: "Clinical" SLEDAI-2K is the SLEDAI-2K score excluding scores attributable to any urinary or laboratory findings (including immunological parameters): .Includes scores for the following clinical items: arthritis, myositis, rash, alopecia, mucosal ulcers, pleurisy, pericarditis, or vasculitis. .Excludes scores attributable to fever, SLE headache, and organic brain syndrome. For patients with lupus nephritis, if there is urine protein > 0.5 g/24h or UPCR > 500 mg/g, or active urinary sediment (urine RBC > 5/HPF or urine WBC > 5/HPF, or RBC casts, or WBC casts, after excluding infection) at screening, the requirement for a "clinical" SLEDAI-2K score >= 4 may not need to be met. 5. Physician's Global Assessment (PGA) score >= 1.0 at screening (0-3 Visual Analogue Scale, VAS). Inclusion Criteria for Patients with SSc: 1. Diagnosis of SSc according to the 2013 ACR/EULAR classification criteria. 2. Diagnosis of diffuse cutaneous SSc at screening. 3. Evidence of active disease, defined as at least one of the following: a) New onset of SSc within 2 years prior to screening. b) New skin involvement or worsening in two new body areas (of the 17 body areas defined by
Exclusion criteria
Exclusion criteria: Patients will not be eligible for enrollment in this study if they meet any of the following exclusion criteria: Exclusion Criteria: 1. Any clinically significant underlying medical condition that, in the investigator's judgment, poses a safety risk or concern, excluding refractory Systemic Lupus Erythematosus (SLE), Systemic Sclerosis (SSc), ANCA-associated Vasculitis (AAV), Idiopathic Inflammatory Myopathies (IIM), Sjögren's Syndrome (SS), Multiple Sclerosis (MS), Neuromyelitis Optica Spectrum Disorders (NMOSD), Myasthenia Gravis (MG), Graves' disease, Autoimmune Encephalitis (AE), Autoimmune Hemolytic Anemia (AIHA), and Immune Thrombocytopenia (ITP). 2. Rapidly progressive glomerulonephritis not directly related to SLE/LN, AAV/AAGN, SSc, or IIM, defined as a = 50% reduction in eGFR within 3 months since diagnosis. 3. Presence of other uncontrolled severe conditions not directly related to the primary disease prior to screening, such as severe hemolytic anemia, severe thrombocytopenic purpura, severe agranulocytosis, severe myocardial damage, severe pneumonia or pulmonary hemorrhage, severe hepatitis, severe vasculitis, or active central nervous system symptoms including cerebrovascular accident, aneurysm, epilepsy, seizures/convulsions, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis, etc. 4. Presence of clinically significant central nervous system disease or pathological changes not attributable to lupus prior to screening, including but not limited to: cerebrovascular accident, aneurysm, epilepsy, seizures/convulsions, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis. 5. For SLE/LN subjects: a) Severe active central nervous system (CNS) lupus, including psychosis, seizures, lupus headache, or other signs or symptoms associated with neuropsychiatric lupus, as determined by a qualified specialist physician during the screening period. b) Drug-induced lupus or secondary lupus. 6. For AAV/AAGN subjects: a) Drug-induced or secondary AAV/AAGN. b) Presence of alveolar hemorrhage requiring invasive ventilatory support at screening. 7. For MG subjects: Presence of uncontrolled myasthenic crisis within 2 weeks prior to screening. 8. For IIM subjects: Presence of severe rhabdomyolysis or CK level >= 120 × ULN at screening. 9. For SSc subjects: a) Presence of scleroderma renal crisis within 1 year prior to screening. b) Presence of cardiac tamponade within 6 months prior to screening. c) Presence of active infection of digital ulcers within 3 months prior to screening. d) Presence of digital gangrene at screening. 10. History of allogeneic bone marrow or stem cell transplantation or solid organ transplantation (e.g., kidney, lung, heart transplant) or planned future such transplantation. 11. Prior history of autologous or allogeneic CAR T-cell therapy. 12. History or current presence of significant cardiovascular dysfunction, including: a) Signs or symptoms of congestive heart failure corresponding to New York Heart Association (NYHA) class >= III within 12 months prior to screening; b) Left ventricular ejection fraction (LVEF) < 50% as shown by echocardiography (assessed at screening); c) Myocardial infarction, unstable angina, uncontrolled or symptomatic atrial arrhythmias, any ventricular arrhythmia, or other clinically significant heart disease within 6 months prior to screening; d) Pul
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| TBNK Assay;Pharmacokinetics(PK); | — |
Secondary
| Measure | Time frame |
|---|---|
| Complete Blood Count(CBC);blood pressure;Blood Biochemistry ;Disease Activity Score;Cytokines;Immunoglobulins;Body Temperature;heart rate;Liver Function;Urinalysis; | — |
Countries
China
Contacts
Public ContactDi Fu/ Jin Li
The First Affiliated Hospital of Guangzhou Medical University
Outcome results
None listed