Safety Study of CC312 in Autoimmune Disease Patients

Inclusion Criteria

• •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.
• •For SLE:
• •1. Subjects who are diagnosed with SLE according to the 2019 European League Against Rheumatism (EULAR)/1997 American College of Rheumatology (ACR) diagnostic classification criteria;
• •2. SLEDAI-2000 score of ≥ 8 points and at least one BILAG grade A or two BILAG grade B under standard treatment conditions;
• •3. Meet one of the following conditions: antinuclear antibody (ANA) determined to be positive during the screening period, or anti-dsDNA antibodies higher than normal levels at screening, or anti-Sm antibodies higher than normal levels at screening;
• •4. Before the first dose of the investigational drug, subjects must have received at least one of the following standard treatments for 12 weeks, and the dose must have been stable for at least 30 days (dose reduction is allowed and dose increase is not allowed ). Standard treatment regimen refers to the stable use of any of the following (alone or in combination): a. Antimalarial (hydroxychloroquine) monotherapy; b. Antimalarials in combination with oral corticosteroids (OCS, e.g., prednisone or other hormones at equivalent doses) and/or immunosuppressants (including mycophenolate mofetil, cyclophosphamide, leflunomide, methotrexate, tacrolimus, ciclosporin, azathioprine, Tripterygium wilfordii); c. OCS and/or immunosuppressant combination therapy. If the subject is receiving OCS (e.g., prednisone or other hormones at equivalent doses), the following criteria must be met: at screening and during the screening period, the maximum dose of OCS is 30 mg/day of prednisone (or other hormones at equivalent doses); other drugs and traditional Chinese medicines that affect immunity may be continued at the discretion of the investigator.
• •For IIM:
• •1. According to the 2017 EULAR/ACR Classification Criteria, diagnosed as possible or definite IIM-possible IIM: with a score of 5.5 points without biopsy; definite IIM: with a score of 6.7 points with biopsy;
• •2. Meeting one of the following criteria: During or before the screening period, confirmed to have at least one positive myositis-specific autoantibody (MSA), myositis-associated autoantibody (MAA), or ANA;
• •3. Conventional treatment is ineffective or the disease relapses after remission. Conventional treatment is defined as: the use of glucocorticoids (prednisone \>1 mg/kg/d or equivalent dose) and/or at least one immunomodulatory drug: such as antimalarial drugs, azathioprine, mycophenolate mofetil, cyclophosphamide, methotrexate, tacrolimus, ciclosporin, and/or biological drug products: such as rituximab and belimumab.
• •For IIM:
• •1. Subjects who are diagnosed with SSc according to the 2013 EULAR/ACR diagnostic classification criteria;
• •2. Meets one of the following criteria: positive ANA confirmed during or before the screening period, or at least one positive SSc-related antibody profile (such as Scl70, Th/To, RP11/12, U3RNP autoantibodies);
• •3. Conventional treatment is ineffective or the disease relapses after remission. Conventional treatment is defined as: using glucocorticoids (prednisone \> 0.5 mg/kg/d or equivalent dose) and cyclophosphamide, and any of the following immunomodulatory drugs: such as antimalarial drugs, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, ciclosporin, and/or biological agents: such as rituximab and belimumab, with a cumulative treatment duration \> 6 months.
• •For RA:
• •1. Diagnosed with RA according to the 2010 EULAR/ACR diagnostic classification criteria;
• •2. Disease Activity Score DAS28-ESR \>3.2 (i.e., moderate activity or higher) during the screening period;
• •3. Failure after treatment with at least one conventional disease-modifying antirheumatic drug (DMARD) and/or at least one targeted synthetic DMARD (tsDMARD)/biologic DMARD (bDMARD) (defined as no remission after at least 3 months of treatment);
• •4. At screening, if the subject is taking prednisone or an equivalent dose of a glucocorticoid, the dose must be ≤10 mg/day and stable for at least 4 weeks before the first dose;
• •5. The subject must have discontinued traditional Chinese medicine for the treatment of RA for ≥4 weeks before the first dose;
• •6. Other DMARDs, except for methotrexate (MTX) (subjects who have been on routine MTX treatment for 12 weeks before enrollment, with a stable MTX dose for 4 weeks before enrollment), must meet the washout period requirements: discontinuation of conventional synthetic DMARDs (csDMARDs) (including but not limited to sulfasalazine, leflunomide, penicillamine, azathioprine, ciclosporin A, cyclophosphamide, hydroxychloroquine, etc.) and herbal agents (including Tripterygium wilfordii, total glucosides of paeony, sinomenine, etc.) for 4 weeks before the first dose; discontinuation of intra-articular, intramuscular, or intravenous corticosteroids for 4 weeks before the first dose; discontinuation of anakinra and etanercept for 4 weeks before the first dose; discontinuation of adalimumab and infliximab for 8 weeks before the first dose; discontinuation of golimumab, certolizumab pegol, and tocilizumab for 10 weeks before the first dose; discontinuation of abatacept for 12 weeks before the first dose; in addition, stable doses of nonsteroidal anti-inflammatory drugs (NSAIDs) are permitted to be continued.
• •For ITP:
• •1. Diagnosed with ITP according to the diagnostic criteria of the Chinese Guideline on the Diagnosis and Management of Adult Primary Immune Thrombocytopenia (2020 Edition);
• •2. Ineffective response or relapse after at least one prior treatment regimen (including but not limited to TPO mimetics/agonists, corticosteroids, immunoglobulins, azathioprine, cyclophosphamide, and/or rituximab);
• •3. At least 2 platelet count measurements (with an interval of more than 24 hours) from the screening period to before the first dose, with an average platelet count \<30×109/Land no single platelet count\>35×109/L;
• •4. If receiving standard background therapy for ITP, the dose and frequency of this therapy should be stable for at least 4 weeks (dose change ≤10%) before the first dose.
• •For AIHA:
• •1. Diagnosed with AIHA according to the diagnostic criteria of the Chinese Guideline on the Diagnosis and Management of Autoimmune Haemolytic Anaemia (2022 Edition);
• •2. Poor response after at least first-line treatment (corticosteroids);
• •3. Presence of anaemia-related symptoms during the screening period;
• •4. The dose of supportive care must be stable for at least 4 weeks before the first dose.
• •Laboratory test results:
• •Complete blood count:
• •1. SLE, SSc, and IIM: Absolute neutrophil count ≥1.0 x109/L, haemoglobin ≥60 g/L, platelets ≥50 x109/L;
• •2. RA: Neutrophil count ≥1.5 x109/L, haemoglobin ≥90 g/L, platelets ≥100 x109/L;
• •3. ITP: Absolute neutrophil count ≥1.0 x109/L, haemoglobin ≥70 g/L, platelets ≥10 x109/L;
• •4. AIHA: Absolute neutrophil count ≥1.0 x109/L, platelets ≥50 x109/L (≥10 x109/L for patients with Evans syndrome and transfusion is permitted).
• •Liver function: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \<3 times the upper limit of normal (ULN), and total serum bilirubin ≤1.5×ULN (≤3.0×ULN for Gilbert's syndrome) or if bilirubin abnormality is caused by the study disease, participation is allowed upon investigator's judgment.
• •Renal function: For RA, ITP, and AIHA: Serum creatinine ≤1.5 times ULN, or calculated creatinine clearance \>50 mL/min (Cockcroft-Gault formula).
• •Left ventricular ejection fraction (LVEF) ≥50%.
• •Female subjects of childbearing potential must agree to use effective contraception from the screening period until 6 months after the last dose. Additionally, they must agree to refrain from collecting or donating eggs during this period; any male partners of reproductive potential must also agree to use effective contraceptive measures during this period.
• •Male subjects with reproductive potential must agree to use effective contraception from the screening period to 6 months after the last dose, and have no plans for reproduction or sperm donation. During this period, their female partners of childbearing potential must also agree to use effective contraception.