This study is an open-label, multiple-dose escalation, Investigator-Initiated Trial (IIT) clinical trial designed to evaluate the safety and tolerability of CC312 in adult patients with relapsed and refractory autoimmune diseases. The trial also assesses pharmacokinetics (PK) and preliminary efficacy.
CC312 is a trispecific T cell engager (TriTE) that targets the B cell surface antigen CD19, the T cell antigen CD3, and the T cell co-stimulatory molecule CD28. Given its mechanism of action, which is similar to the "biopharmaceutical version" of CAR-T, there is a higher risk of cytokine release syndrome (CRS) at the onset of infusion administration. Therefore, a lower priming dose will be administered before the therapeutic dosing phase to mitigate this risk and ensure safety, followed by a therapeutic dose to achieve and maintain efficacy.
The study is divided into three dose groups, with 3-6 subjects enrolled in each group, resulting in a total of 9-18 subjects in the study. A "3+3" dose escalation design is employed to systematically evaluate the safety and determine the optimal dose of CC312.
Subjects who fully understand the objectives, nature, methods of the study, and possible adverse reactions, voluntarily participate as subjects, and sign the informed consent form (ICF).
Age ≥18 years (inclusive, based on the time of signing ICF), male or female.
Subjects who are diagnosed with SLE according to the 2019 European League Against Rheumatism (EULAR)/1997 American College of Rheumatology (ACR) diagnostic classification criteria;
SLEDAI-2000 score of ≥ 8 points and at least one BILAG grade A or two BILAG grade B under standard treatment conditions;
Subjects who have severe lupus nephritis (defined as urinary protein >6 g/24 h or serum creatinine >2.5 mg/dL or 221 μmol/L), or required treatment of active nephritis with protocol-prohibited drugs, or required hemodialysis or received prednisone ≥100 mg/d or equivalent glucocorticoid therapy for ≥14 days within 8 weeks before screening.
Subjects who have central nervous system diseases caused by SLE or not caused by SLE within 8 weeks before screening (including but not limited to epilepsy, psychosis, posterior reversible encephalopathy syndrome, cerebrovascular accident, encephalitis, central nervous system vasculitis, etc.).
Other types of IIM: inclusion body myositis, diabetic amyotrophy, juvenile myositis; severe muscle injury or myositis causing permanent weakness or cardiac involvement due to non-IIM causes (e.g., stroke).
Pulmonary arterial hypertension associated with SSc requiring treatment; or rapidly progressive SSc-related lower gastrointestinal tract (small and large intestine) involvement (requiring parenteral nutrition), active antral vascular ectasia; previous renal crisis caused by SSc.