Safety Study of CC312 in Autoimmune Disease Patients

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.


Eligibility Criteria:
Inclusion Criteria:

* Diagnosed with Systemic Lupus Erythematosus (SLE) according to the diagnostic classification criteria of the 2019 European League Against Rheumatism (EULAR) / 1997 American College of Rheumatology (ACR).
* With standard treatment, the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2000) score is ≥8 points, and there is at least one British Isles Lupus Assessment Group (BILAG) A level or two BILAG B levels.
* Meets one of the following conditions: positive antinuclear antibody (ANA) determined during the screening period, or anti-dsDNA antibody above the normal level during screening, or anti-Sm antibody above the normal level during screening.
* Before the first administration of the trial drug, the subject has received at least one of the standard treatments for 12 weeks, and the dose must be stable (reduction is allowed, increase is not allowed) for at least 30 days.

Exclusion Criteria:

* Severe lupus nephritis (defined as proteinuria \>6 g/24 hours or serum creatinine \>2.5 mg/dL or 221 μmol/L) within 8 weeks prior to screening, or active nephritis requiring treatment with drugs prohibited by the protocol, or requiring hemodialysis or treatment with prednisone ≥100 mg/d or equivalent glucocorticoids for ≥14 days.
* Central nervous system disorders caused by SLE or non-SLE within 8 weeks prior to screening (including but not limited to epilepsy, psychosis, interstitial encephalopathy syndrome, cerebrovascular accident, encephalitis, central nervous system vasculitis, etc.).
* History of major organ transplantation (such as heart, lung, kidney, liver) or hematopoietic stem cell/bone marrow transplantation.
* Concurrent presence of two or more immune diseases requiring systemic treatment, deemed unsuitable for enrollment by the investigator.

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

* Participation in any other clinical trial (including cell or gene therapy) within 4 weeks prior to screening or within 5 half-lives of the investigational.
* Vaccination with live/attenuated vaccines within 4 weeks prior to screening or planned vaccination with live/attenuated vaccines during the trial period.
* Active severe infection requiring antibiotic treatment within 14 days prior to screening.
* History of Grade 3 to 4 allergic reactions Common Terminology Criteria for Adverse Events(CTCAE) version 5.0 to another monoclonal antibody therapy, or known allergy to any component or excipient of the CC312 drug formulation (including recombinant protein, polysorbate 80, etc.); Patients with ≤ Grade 3 allergic reactions lasting less than 24 hours may participate in this study after discussion with the investigator.
* Admission or evidence of the use of illicit drugs, drug abuse, or alcoholism.
* Major surgery within 4 weeks prior to screening or minor surgery within 2 weeks prior to screening; wounds must be fully healed (surgical procedures such as catheter placement are not exclusion criteria).
* History of any of the following cardiovascular diseases within 6 months prior to screening: heart failure defined as Class III or IV by the New York Heart Association (NYHA), myocardial infarction, unstable angina, uncontrolled or symptomatic atrial arrhythmias, any ventricular arrhythmias, or other clinically significant heart diseases.
* Any other serious underlying disease that may interfere with the planned dosing, treatment, and follow-up, affect patient compliance, or pose a higher risk of complications as judged by the investigator (e.g., active peptic ulcer, uncontrolled epilepsy, cerebrovascular event, gastrointestinal bleeding, severe signs and symptoms of coagulation dysfunction, heart disease), psychiatric illness, psychological, familial, or geographically related diseases.
* Evidence of concurrent malignancy within \< 5 years prior to screening, except for adequately treated cervical carcinoma in situ, localized cutaneous squamous cell carcinoma, basal cell carcinoma, localized prostate cancer, ductal carcinoma in situ of the breast, or ≤ T1 urothelial carcinoma. Patients with prostate cancer under active surveillance are eligible for this study.
* Pregnant or breastfeeding women.
* Subjects with positive results for human immunodeficiency virus antibody (HIV-Ab), hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV-Ab), or Treponema pallidum antibody (TP-Ab) in serological tests during the screening period.
* Subjects with active or latent tuberculosis (T-SPOT positive) detected during the screening period.
* Other subjects who are deemed by the investigator to be unsuitable for participation in this trial.