This study is an open-label, multiple ascending dose investigator-initiated trial (IIT) designed to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of CC312 in adult patients with relapsed or refractory autoimmune diseases.
Fully understand the trial's purpose, nature, methodology, and potential adverse reactions, voluntarily participate as a subject, and sign the informed consent form.
Aged 18-65 years (inclusive, based on the date of signing the informed consent form), regardless of gender.
Diagnosed with SLE according to the 2019 EULAR/ACR classification criteria；
Meet at least one of the following: positive antinuclear antibody (ANA) and/or anti-dsDNA antibody and/or anti-Sm antibody at screening；
Severe lupus nephritis within 8 weeks prior to screening (defined as urinary protein >6 g/24 h, serum creatinine >2.5 mg/dL or 221 μmol/L), requirement of prohibited medications for active nephritis per protocol, need for hemodialysis, or receipt of prednisone ≥100 mg/day (or equivalent glucocorticoids) for ≥14 days.
Central nervous system disorders (including but not limited to epilepsy, psychosis, interstitial encephalopathy syndrome, cerebrovascular accident, encephalitis, or CNS vasculitis) within 8 weeks prior to screening.
Other types of idiopathic inflammatory myopathies: inclusion body myositis, amyotrophic diabetes, or juvenile myositis; patients with severe muscle damage or permanent weakness/cardiac involvement due to non-IIM causes (e.g., stroke).
SSc-related pulmonary hypertension requiring treatment; rapidly progressive SSc-related lower gastrointestinal (small/large intestine) involvement requiring parenteral nutrition; active gastric antral vascular ectasia; history of SSc-related renal crisis.
Single group
CC312
Biological/VaccineThe priming dose of CC312 will be administered intravenously on Day -3, followed by safety and tolerability evaluations on Day -1 (3 days post-first dose). The first therapeutic dose of CC312 will be administered on Day 1, with subsequent doses administered on Day 4, 8, and 11. Corresponding safety and tolerability assessments will be performed with each dose. Based on the evaluation of clinical efficacy, B-cell depletion, and safety/tolerability profile at the end of Day 14, the dose for the subsequent therapeutic dosing will be determined (maintained or escalated). Thereafter, therapeutic dosing will be administered on Days 15, 18, 22, and 25, accompanied by scheduled safety and tolerability assessments.
Dose-limiting toxicity (DLT)
A Dose-Limiting Toxicity (DLT) is defined as any adverse event occurring within the 29-day period following the initiation of CC312 intravenous infusion during the dose-escalation phase, assessed by the investigator as related to CC312 and meeting the following criteria: (1) Hematologic Toxicity: Grade 4 toxicity (excluding lymphopenia) persisting beyond 29 days and not attributable to underlying disease; (2) Non-Hematologic Toxicity: Any ≥Grade 4 toxicity potentially related to CC312 during the observation window, or any Grade 3 toxicity potentially related to CC312 that fails to resolve to ≤Grade 2 within 7 days.
Adverse events (AE)/serious adverse events (SAE)
With the exception of CRS and ICANS, which will be graded according to the ASTCT criteria, the severity of all other adverse events (AEs) will be assessed and classified using the CTCAE (Common Terminology Criteria for Adverse Events) version 5.0.
Serum Concentration of CC312
All subjects are required to undergo blood sampling for serum concentration analysis at the following time points: within 1 hour before the guide dose (0 h) and 1 hour after infusion; for the treatment dose, within 1 hour before administration (0 h) and 1 hour after infusion on the first and second dosing occasions of the first and third treatment weeks, within 1 hour before administration (0 h) and 1 hour after infusion on the first dosing occasion of the second and fourth treatment weeks; and at early withdrawal/end of study (EOS).
Counts of peripheral B cells
All subjects are required to undergo blood sampling for peripheral B cells analysis at the following time points:within 1 hour before the priming dose (0 h), and 1 hour and 24 hours after infusion; for the treatment dose, within 1 hour before administration (0 h) and 1 hour and 24 hours after infusion on the first and second dosing occasions of Weeks 1 and 3, within 1 hour before administration (0 h) on the first dosing occasions of Week 2 and Week 4; if dosing is extended beyond Day 28, within 1 hour before the second weekly dose until the end of the extended dosing period; after the last dose, once monthly for 4 consecutive months; during the long-term follow-up period, once every 3 months; and at early withdrawal/end of study (EOS).
Cytokines
All subjects are required to undergo blood sampling for cytokine analysis (IFN-γ、IFN-α、IL-2、IL-6、IL-10、TNF-α) at the following time points: within 1 hour before the priming dose (0 h), and 1 hour and 24 hours after infusion; for the treatment dose, within 1 hour before administration (0 h) and 1 hour and 24 hours after infusion on the first and second dosing occasions of Weeks 1 and 3; within 1 hour before administration (0 h) and 1 hour and 24 hours after infusion on the first dosing occasion of Weeks 2 and 4; and at early withdrawal/EOS.
Complement
Blood samples for complement analysis will be collected from all subjects at the following time points: Screening/Baseline, within 1 hour before the priming dose (0 h); for the treatment dose, within 1 hour before the first weekly administration at Weeks 1, 2, 3, and 4, and at Weeks 8, 12, 24, and 48, as well as at early withdrawal.
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