Phase II Study of Hemay005 in Patients With Active Ulcerative Colitis

Exclusion Criteria

• •Pregnant or lactating women, or women or men whose partners planning to become pregnant during the study;
• •Knownto be allergic to any component of Hemay005 tablets (the main component is hemay005, and the main excipients are mannitol, low substituted hydroxypropyl cellulose, croscarmellose sodium and magnesium stearate);
• •Patients with suspected or confirmed Crohn's disease, undiagnosed types of colitis, fulminant colitis, toxic megacolon, microscopic colitis, ischemic colitis or radioactive colitis based on medical history and endoscopy and/or histological results;
• •Patients with active EBV and/or CMV infection (EBV antibody IgM and/or EBV DNA positive); CMV antibody IgM and/or CMV DNA positive);
• •Patients with the disease confined to the rectum (ulcerative proctitis) according to the endoscopy during screening;
• •Patients who have undergone surgical treatment for ulcerative colitis or who require surgery during the study;
• •Patients with active infection or positive pathogen test at the time of screening, and determined by the investigator to increase the risk of the subject, except for those with negative repeat test results and no symptoms of persistent infection (if time permits, during screening treatment and repeat testing);
• •Patients receiving the following treatments:
• •Patients who have used azathioprine/6-mercaptopurine, methotrexate within 7 days before randomization; Patients who have used cyclosporine, mycophenolate mofetil, tacrolimus/sirolimus within 4 weeks before randomization; Patients who have used interferon within 8 weeks before randomization; Patients who have received anti-TNF-α treatment within 8 weeks before randomization; Intravenous corticosteroids or rectal administration of corticosteroids or rectal administration of 5-ASA within 2 weeks prior to randomization; Patients who have used thalidomide within 8 weeks before randomization;Patients who have received antibiotic treatment within 1 week before randomization;
• •Patients with active infection and judged by the investigator to increase the risk of the subjects;
• •Patients with a history of TB or active TB (Investigator-judged signs or symptoms of active tuberculosis at screening):
• •Screening was permitted if patients had a history of tuberculosis and had been cured by investigator assessment for at least 3 years prior to randomization; subjects with a negative T-cell test for tuberculosis infection (T-SPOT) at screening can be included in this study. Subjects who are T-SPOT positive during the screening period need to undergo tuberculosis-related clinical examinations (Tuberculosis-related clinical work performed within 12 weeks prior to randomization can be used directly for evaluation), if the tuberculosis-related clinical examination confirmed active tuberculosis, the subjects will not be eligible for this study. Subjects can be included in this study if the tuberculosis-related clinical examination confirms inactive tuberculosis. If the research center cannot perform T-SPOT test, TB screening by QuantiFERON-TB Gold test kit can also be accepted. The treatment of QuantiFERON-TB-Gold screening results is the same as that of T-SPOT.
• •Patients with hemoglobin \<8 g/dL or hematocrit \<30%, white blood cells \<3.0 × 10\^9/L or neutrophils \<1.2 × 10\^9/L, platelets \<100 × 10\^09/L at screening;
• •Total bilirubin (TBIL), aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥ 2 upper limits of normal (ULN) at screening;
• •Glomerular filtration rate (eGFR) ≤ 40 ml/min;
• •Patients with hereditary immunodeficiency disease;
• •Patients with a history of lymphoproliferative disorders (e.g. EBV-related lymphoproliferative disorders), or with lymphoma, leukemia, myeloproliferative disease, multiple myeloma;
• •Lymphocyte apheresis or selective mononuclear granulocyte apheresis was performed within 12 months before the screening or is planned to be performed during the study;
• •Patients with malignant tumor or with a history of malignancy other than well-treated or resected basal cell or squamous cell skin cancer;
• •Patients with conditions that may affect oral drug absorption, e.g. gastrectomy or clinically significant diabetes-related gastrointestinal disorders, or specific types of obesity surgery such as gastric bypass, however, patients only subjected to the division of the stomach into independent chambers, like gastric banding, will not be excluded;
• •Patients with previous surgery on small intestine or colon and with evidence of colonic dysplasia or intestinal stenosis;
• •Patients with chronic hepatitis B virus (HBV) infection (hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb) and hepatitis B core antibody (HBcAb) should be assessed for all patients during screening: patients with positive hepatitis B surface antigen (HBsAg) will be excluded; patients with HBsAg (negative), HBsAb (negative or positive) and HBcAb (positive) should be tested for HBV-DNA, and if the HBV-DNA result is positive, patient will be excluded; if the HBV-DNA result is negative, patients can be enrolled in the study.), chronic hepatitis C virus (HCV) infection (patients with positive hepatitis C virus antibody (HCVAb) excluded) or human immunodeficiency virus (HIV) infection (patients with positive human immunodeficiency virus (HIV) antibody excluded) or Syphilis (TP) infection (excluded patients with Treponema pallidum antibody (Anti-TP) positive);
• •Patients receive any live vaccine at present or has received any live vaccine within 8 weeks prior to randomization, or have been vaccinated against COVID-19 within 14 days prior to randomization;
• •Use of cytochrome P450 enzyme inducers (such as rifampicin, phenobarbital, dexamethasone, isoniazid, carbamazepine, etc.) within 14 days before screening;
• •Suicidal behavior (including active attempts, interrupted attempts, or attempted attempts) or suicidal thoughts within the past 6 months;
• •Other conditions that the investigator judges as unsuitable to participate in the study.