Hemay005 for the Treatment of Chinese Moderately to Severely Active Ulcerative Colitis

This study is a phase 3, multicenter, randomized, double-blinded, placebo-controlled, parallel-group study to examine the efficacy, safety of Hemay005 in induction and maintenance therapy in Chinese patients with moderately or severely active ulcerative colitis. The study consists of two independent phases: an 12-week Induction Phase (might including an 12-week Extended Induction phase, depending on the participant status by the end of the induction treatment) and a 40-week Maintenance Phase. Screening period will be up to 5 Weeks.

In the Induction Phase, participants will be randomized 2:1 to receive either Hemay005 (twice daily) or placebo for 12 weeks. The randomization will be stratified by: exposed to advanced therapy (yes/no); disease severity (modified Mayo score of 5-6 or 7-9) and baseline corticosteroid use (yes/no). Participants who have not show clinical response (either receive Hemay005 or placebo) by week 12 will undergo an extended 12-week induction treatment with Hemay005.

After completing the Induction Phase (or the Extended Induction Phase), participants with response are eligible to go to the Maintenance Phase. Participants with a response to Hemay005 by week 12 of the Induction Phase and those with a response by the end of the Extended Induction Phase) will be randomized 1:1 to receive either Hemay005 (twice daily) or placebo for 40 weeks. Randomization will be stratified by corticosteroid use at the start date of Maintenance Phase (yes/no) and clinical remission status by the end of Induction Phase (yes/no). Participants who are assigned to placebo during the Induction Phase and have demonstrated a clinical response will continue to receive blinded placebo during the Maintenance Phase. Participants who have not showed a clinical response by week 12 of the Induction Phase but have a response to Hemay005 by the end of the Extended Induction Phase will continue to receive blinded Hemay005 during the Maintenance Phase.

During the Maintenance Phase, participants who are demonstrated loss of response will be eligible to go to the open-label treatment phase and treated with Hemay005. The total duration of open-label treatment phase will not exceed 40 weeks since the participant enrolled into the Maintenance Phase.

Inclusion criteria

• Men or women 18 to 80 years of age, inclusive, at the time of consent.
• Voluntarily to give written informed consent.
• Diagnosed with UC established at least 3 months prior to screen visit. The diagnosis must be confirmed by clinical and endoscopic evidence, corroborated by a histopathology report.
• Active UC confirmed by endoscopy, classified as Montreal E2 or E3.
• Moderately to severely active UC, defined as mMS of 5 to 9 points, including a MES of at least 2 (confirmed through centrally read endoscopy) and a SFS of at least 1 and a RBS of at least 1. The endoscopy should be performed within 14 days prior to randomization.
• Demonstrated inadequate response, loss of response and/or intolerance to at least one of the following UC therapies:

A) Conventional therapies, including oral 5-aminosalicylic acid (5-ASA) compounds, corticosteroids, immunoregulatory agents.

B) Advanced therapies: biologics (including but not limit to antitumor necrosis factor alpha (TNFα) antibodies, anti-integrin antibodies, anti-interleukin 12/23 antibodies) and small molecule therapies(including but not limit to JAK inhibitors, S1P receptor modulators) Note: The medication used to qualify the subject for entry into this category must be approved for the treatment of UC in the country of use and the subject must have received an adequate course of therapy based on local guidelines for that therapy.

• For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use adequate contraception and agreement to refrain from egg donation or undergo fertility treatment during the treatment period and for 30 days after the final dose of Hemay005. For male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agree to refrain from donating sperm during the treatment period and for 30 days after the final dose of Hemay005.

Exclusion criteria

• Current diagnosis of CD, abdominal/intrabdominal/perianal fistula and/or abscess, indeterminant colitis, IBD-unclassified, microscopic colitis, ischemic colitis, infectious colitis, radiation colitis, or active diverticular disease.
• Severe UC as evidenced by any of the following:

A) Hospitalization for the treatment of UC ≤ 2 weeks prior to screening or, in the physician's judgement, is likely to require hospitalization for medical care or surgical intervention of any kind for UC during the study.

B）Current evidence of fulminant colitis, toxic megacolon, or recent history (within 6 months) of toxic megacolon, or bowel perforation.

C）Prior history of subtotal, or total colectomy.

• Past or current evidence of any gastrointestinal malignancy, either prior to or at the time of screening. History of malignancy within 5 years prior to screening visit, with the exception of malignancies adequately treated with resection for non-metastatic basal cell or squamous cell cancer or in situ cervical cancer.
• Past or current evidence of definite low-grade or high-grade colonic dysplasia or adenomas or neoplasia not completely removed.
• Significant uncontrolled medical comorbidity (such as cardiac, pulmonary, renal, hepatic, endocrine, ), psychiatric, or other condition that in the opinion of the investigator, would confound the study results, compromise patient safety, interfere with the potential participant's provision of informed consent, or compliance with trial procedures.
• Evidence of infection with Clostridioides difficile (C. difficile; formerly known as Clostridium difficile), cytomegalovirus (CMV), human immunodeficiency virus (HIV), Hepatitis B (HBV), Hepatitis C (HCV).
• Evidence of active tuberculosis (TB).
• Any condition that would preclude endoscopic evaluation.
• Either received protocol-specified prohibited medicines prior to baseline endoscopy and/ or randomization, or have not be washed out sufficiently due to the protocol before baseline endoscopy and/ or randomization.