Safety and Efficacy Study of CC312 for Moderate to Severe SLE

Inclusion Criteria:

• Fully understand the trial's purpose, nature, methodology, and potential adversereactions, voluntarily participate as a subject, and sign the informed consent form.

• Aged 18 to 65 years (inclusive, based on the date of signing the informed consentform), regardless of gender.

• Diagnosed with systemic lupus erythematosus (SLE) according to the 2019 EULAR/ACRclassification criteria.

• SLEDAI-2000 score ≥7 with at least one BILAG A or two BILAG B domains, despitestandard therapy.

• Meet at least one of the following criteria: positive antinuclear antibody (ANA) ≥1:80 at screening, positive anti-dsDNA antibody at screening, or positive anti-Smantibody at screening.

• Have had an inadequate response to at least two standard therapies (e.g.,corticosteroids, antimalarials, immunosuppressants, biologics) prior to screening,including at least one immunosuppressant and/or biologic. Prior to the first dose,subjects must have been on a stable dose of corticosteroids (e.g., ≤40 mg/dayprednisone or equivalent at screening and during the screening period; if usedalone, ≥7.5 mg/day prednisone or equivalent) and/or antimalarials and/orimmunosuppressants for at least 12 weeks, with doses stable for ≥30 days.

• Females of childbearing potential must agree to use highly effective contraceptionfrom screening until 6 months after the last dose and refrain from oocyte collectionor donation during this period. Their male partners of childbearing potential mustalso use effective contraception.

• Males of childbearing potential must agree to use highly effective contraceptionfrom screening until 6 months after the last dose, with no plans for fertility orsperm donation. Their female partners of childbearing potential must also useeffective contraception during this period.

Exclusion Criteria:

• Severe lupus nephritis within 8 weeks prior to screening (defined as urinary protein >6 g/24 h, or serum creatinine >2.5 mg/dL or 221 μmol/L, or requiring prohibitedmedications for active nephritis per protocol, or needing hemodialysis, or receivingprednisone ≥100 mg/d or equivalent glucocorticoids for ≥14 days).

• Central nervous system disorders (including but not limited to epilepsy, psychosis,interstitial encephalopathy syndrome, cerebrovascular accident, encephalitis, CNSvasculitis) within 8 weeks prior to screening, whether SLE-related or not.

• History of major organ transplantation (e.g., heart, lung, kidney, liver) orhematopoietic stem cell/bone marrow transplantation.

• Other concurrent autoimmune diseases requiring systemic therapy, except forSjögren's syndrome.

• IgA deficiency (serum IgA level <10 mg/dL).

• Abnormal laboratory findings at screening:

Liver function: AST/ALT or total bilirubin >2× upper limit of normal (ULN); Hematology: hemoglobin <85 g/L, WBC <2.5×10⁹/L, neutrophil count <1.0×10⁹/L, platelet count <50×10⁹/L; Renal function: eGFR <30 mL/min/1.73 m²;

• Participation in any other clinical trial (including cell or gene therapy) within 4weeks prior to screening or within 5 half-lives of the investigational product (whichever is longer).

• Received CAR-T therapy within 6 months prior to screening.

• Treatment with B-cell-depleting agents (e.g., rituximab, or therapies targetingCD19/CD20/BAFF) within 6 months prior to screening, unless B-cell levels havereturned to pre-treatment or normal ranges.

• Received non-standard anti-SLE therapies (e.g., Saphnelo) within 3 months or 5half-lives of the drug (whichever is longer) prior to screening.

• Received live/attenuated vaccination within 4 weeks prior to screening or plans toreceive such during the trial.

• Active infection within 14 days prior to screening (bacterial, viral, fungal,parasitic, or other).

• History of Grade 3-4 allergic reaction (per CTCAE v5.0) to another monoclonalantibody, or known hypersensitivity to any component of CC312 (including recombinantproteins, polysorbate 80, etc.). Patients with transient (≤24 h) Grade ≤3 reactionsmay be included after discussion with the investigator.

• Evidence of drug abuse, substance abuse, or alcohol addiction.

• Major surgery within 4 weeks or minor surgery within 2 weeks prior to screening;wounds must be fully healed (procedures like catheter placement are excluded).

• History of cardiovascular events within 6 months prior to screening: NYHA ClassIII/IV heart failure, myocardial infarction, unstable angina,uncontrolled/symptomatic atrial arrhythmia, ventricular arrhythmia, or otherclinically significant cardiac conditions.

• Any other severe underlying disease (e.g., active gastric ulcer, uncontrolledseizures, cerebrovascular events, GI bleeding, severe coagulation disorders),psychiatric disorder, or social circumstances that may interfere with trial conduct,compliance, or pose high risk per investigator's judgment.

• Concurrent malignancy diagnosed within <5 years prior to screening.

• Grade ≥2 bleeding within 30 days prior to screening, or requiring long-termanticoagulants (e.g., warfarin, LMWH, factor Xa inhibitors).

• Pregnant or lactating women.

• Positive screening for: tuberculosis (PPD skin test or TB-IGRA, unless with prioradequate anti-TB treatment and no current signs), HIV antibody, HBsAg or HBcAb, HCVantibody, or TP antibody.

• Any other condition deemed ineligible by the investigator.