Clinical Study of (A-319) in the Treatment of Active Rheumatoid Arthritis

Exclusion Criteria

• •Subjects with other autoimmune diseases that the investigator considers would not potentially benefit from A-319 treatment; or conditions that interfere with the assessment of joint swelling and pain. 2. Use of abatacept, infliximab, adalimumab, or tocilizumab within 6 weeks prior to the first treatment with the study drug; use of etanercept, anakinra, immune globulin, or blood products within 4 weeks prior to the first treatment with the study drug; or use of a JAK inhibitor (e.g., tofacitinib, baricitinib, or upadacitinib), mycophenolate mofetil, cyclosporine, or iguratimod within 2 weeks prior to the first treatment with the study drug.
• •3\. Use of B-cell depleting therapy, such as rituximab, within 3 months prior to the first treatment with the study drug; cell counts must have returned to acceptable levels or baseline.
• •4\. Subjects with any periprosthetic joint infection. 5. Patients with immunodeficiency (defined as immunoglobulin G ≤ 5g/L). 6. History of demyelinating diseases, including, but not limited to, multiple sclerosis, Guillain-Barré syndrome, and neuromyelitis optica (Devic's disease). 7. Laboratory values: Hemoglobin level \< 9.0 g/dL, absolute white blood cell (WBC) count \< 3.0 × 109/L (\< 3000/mm3), or absolute neutrophil count \< 1.2 × 109/L (\< 1200/mm3), or absolute lymphocyte count \< 0.8 × 109/L (\< 800/mm3); thrombocytopenia, defined as a platelet count \< 100 × 109/L (\< 100,000/mm3); age-appropriate estimated glomerular filtration rate (eGFR) \< 45 mL/min/1.73 m2, proteinuria ≥ 3+; total bilirubin (T-bili), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) exceeding 1.5 times the upper limit of normal (ULN). 8. Receipt of live or live attenuated vaccines within 30 days prior to first medication use.
• •9\. Active hepatitis during the screening period, or positive hepatitis B virus surface antigen (HBsAg), or positive hepatitis B virus core antibody (HBcAb) plus hepatitis B virus (HBV) deoxyribonucleic acid (DNA), or positive hepatitis C virus (HCV) antibody plus HCV RNA; history of human immunodeficiency virus (HIV) infection, or positive HIV antibody during the screening period; or positive Treponema pallidum antibody during the screening period.
• •10\. Chronic active infection or acute infection requiring systemic treatment with antibiotics, antivirals, antiparasitics, or antifungals within 2 weeks prior to screening, or superficial skin infection requiring treatment within 1 week prior to screening (Note: Patients can be rescreened after the infection is resolved). 11. Major surgical procedure (craniotomy, thoracotomy, or laparotomy) or unhealed wounds, ulcers, or fractures within 4 weeks prior to the first dose of study drug, or plans for major surgery during the study.
• •12\. A history of a major clinical illness (such as circulatory system disorders, endocrine system disorders, nervous system diseases, respiratory system diseases, hematologic diseases, immune system diseases, psychiatric disorders, and metabolic instability) that the investigator believes will pose a risk to the patient's safety, or that may affect safety or efficacy analysis if the disease/symptom worsens during the study. For example: Cardiovascular disease: history of acute myocardial infarction, unstable angina, or severe arrhythmias (multi-source frequent premature ventricular contractions, ventricular tachycardia, or ventricular fibrillation) within 6 months prior to screening; New York Heart Association (NYHA) class III-IV.
• •13\. Possible active Mycobacterium tuberculosis infection, defined as: positive sputum smear/sputum culture within 3 months prior to screening/during the screening period, or chest X-ray (anteroposterior and lateral)/lung CT indicating active tuberculosis infection (tuberculosis testing will be performed according to the site's protocol if ethically required).
• •14\. Subjects with a malignancy within 5 years prior to screening (excluding completely cured in situ cervical cancer, non-metastatic squamous cell carcinoma or basal cell carcinoma of the skin, ductal carcinoma in situ of the breast, and papillary thyroid carcinoma).
• •15\. History of major organ transplant (e.g., heart, lung, kidney, liver) or hematopoietic stem cell/or bone marrow transplant).
• •16\. Participation in any clinical trial within 4 weeks prior to the first dose of study drug or within 5 half-lives of the study drug in the clinical trial (whichever is longer, unless otherwise specified).
• •17\. Patients undergoing acute or consolidation medication for depression and experiencing suicidal thoughts within 6 months. 18. Women who are pregnant or breastfeeding, or who plan to become pregnant or breastfeed during the study; or men whose partners plan to become pregnant during the study.
• •19\. Any reason that the researcher deems would prevent the subject from participating in the study.