Phase II Study of Hemay005 in Patients With Active Ulcerative Colitis

Inclusion Criteria:

• Willing to participate in the trial and signing the informed consent forms;

• Age ≥18 years old, male or female;

• Diagnosed as ulcerative colitis (UC) ≥ 3 months at screening with clinicalmanifestations and evidence of endoscopy and confirmed by histopathological reports;

• Expansion of the affected bowel segment beyond the rectum confirmed on endoscopy (affected bowel segment≥15cm);

• Moderate to severe ulcerative colitis with Modified Mayo clinical score (MMCS)≥ 4points and ≤9 points, the Endoscopy subscore ≥ 2 points within 14 days beforerandomization and Stool Frequency subscore ≥ 1 point;

• UC treatment failure or intolerance (intolerance is defined as the discontinuationof drug use due to adverse reactions judged by the investigators) experienced bypatients using at least one of the following:

Oral administration of sulfasalazine (SASP) and/or 5-aminosalicylic acid (5-ASA); Oral administration of corticosteroids; Azathioprine or 6-mercaptopurine; Anti-TNF-α treatment: infliximab or adalimumab, etc.; - If the patient is using the following drugs to treat ulcerative colitis at the time of screening, it is necessary to receive stable treatment during the screening period and the following requirements during the study period are as follows: Oral administration of sulfasalazine (SASP) and/or 5-aminosalicylic acid (5-ASA) maintaining stable for at least ≥ 2 weeks prior to endoscopy during the screening period and maintaining stable during the study period; and/or Oral administration of low-dose corticosteroids (≤25 mg/d prednisolone or equivalent drug dose) maintaining stable for at least ≥ 2 weeks prior to endoscopy during the screening period;

• At least one of the following effective contraceptive methods should be adopted forfemale patients with fertility and male patients who have not undergone vasectomyduring the entire study period from the date of signing the informed consent to 3months after the last dose. Acceptable contraceptive methods in this study include:a. abstinence; b. hormones (oral intake, patch, ring, injection, implantation)combined with male condoms. This measure must be applied at least 30 days prior tothe first administration of investigational drug, otherwise another acceptablemethod of contraception must be used; c. intra-uterine device (IUD) combined withmale condoms; d. barrier method (diaphragm, cervical cap, sponge) combined with malecondoms; exceptional circumstances: a) females who have been menopausal for 5 yearsand more, and b) surgical sterilization (proof should be provided).

Exclusion Criteria:

• Pregnant or lactating women, or women or men whose partners planning to becomepregnant during the study;

• Knownto be allergic to any component of Hemay005 tablets (the main component ishemay005, and the main excipients are mannitol, low substituted hydroxypropylcellulose, 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 orradioactive colitis based on medical history and endoscopy and/or histologicalresults;

• Patients with active EBV and/or CMV infection (EBV antibody IgM and/or EBV DNApositive); CMV antibody IgM and/or CMV DNA positive);

• Patients with the disease confined to the rectum (ulcerative proctitis) according tothe endoscopy during screening;

• Patients who have undergone surgical treatment for ulcerative colitis or who requiresurgery 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 forthose with negative repeat test results and no symptoms of persistent infection (iftime 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 riskof the subjects;

• Patients with a history of TB or active TB (Investigator-judged signs or symptoms ofactive 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/Lor 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-relatedlymphoproliferative disorders), or with lymphoma, leukemia, myeloproliferativedisease, multiple myeloma;

• Lymphocyte apheresis or selective mononuclear granulocyte apheresis was performedwithin 12 months before the screening or is planned to be performed during thestudy;

• Patients with malignant tumor or with a history of malignancy other thanwell-treated or resected basal cell or squamous cell skin cancer;

• Patients with conditions that may affect oral drug absorption, e.g. gastrectomy orclinically significant diabetes-related gastrointestinal disorders, or specifictypes of obesity surgery such as gastric bypass, however, patients only subjected tothe division of the stomach into independent chambers, like gastric banding, willnot be excluded;

• Patients with previous surgery on small intestine or colon and with evidence ofcolonic 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 positivehepatitis B surface antigen (HBsAg) will be excluded; patients with HBsAg (negative), HBsAb (negative or positive) and HBcAb (positive) should be tested forHBV-DNA, and if the HBV-DNA result is positive, patient will be excluded; if theHBV-DNA result is negative, patients can be enrolled in the study.), chronichepatitis C virus (HCV) infection (patients with positive hepatitis C virus antibody (HCVAb) excluded) or human immunodeficiency virus (HIV) infection (patients withpositive 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 14days 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 attemptedattempts) or suicidal thoughts within the past 6 months;

• Other conditions that the investigator judges as unsuitable to participate in thestudy.