A Phase 2 Study to Evaluate the Efficacy, Safety and Pharmacokinetics of SHR-1139 in Patients With Moderate-to-severe Active Ulcerative Colitis

Prior treatment

• Treatment naïve subject diagnosed with Ulcerative Colitis (without previous exposure to any of the following therapies for UC treatment: oral 5-ASA, corticosteroids, immunosuppressants, or biological treatments).
• Subject had previous surgery as a treatment for Ulcerative Colitis or likely to require surgery during the study period.
• Subject is receiving any of the following therapies:
  • 9.1 Cyclosporine, mycophenolate, tacrolimus、JAK inhibitors within 4 weeks prior to baseline.
  • 9.2 Interferon therapy within 8 weeks prior to baseline. 9.3 Intravenous corticosteroids or rectally administered formulation of corticosteroids or 5-ASA within 2 weeks prior to baseline.

Other illness

• Subject has a diagnosis of indeterminate colitis, or clinical findings suggestive of Crohn's Disease.
• Screening endoscopic examination revealed that the subjects had a history of gastrointestinal dysplasia (atypical hyperplasia)/cancer or dysplasia (atypical hyperplasia)/cancer. Except for completely resected low-grade dysplasia.
• Subject has evidence of pathogenic bowel infection. Subjects had Clostridium difficile or other intestinal infection within 30 days of screening endoscopy or test positive at screening for C. difficile toxin or other intestinal pathogens.
• Subject currently has or had:
  • 8.1 A clinically significant infection within 1 month of baseline (e.g., those requiring hospitalization or parenteral antimicrobial therapy or have opportunistic infections).
  • 8.2 A history of more than one episode of herpes zoster, or disseminated zoster (single episode).
  • 8.3 Any infection otherwise judged by the investigator to have the potential for exacerbation by participation in the study.
  • 8.4 Any infection requiring antimicrobial therapy within 2 weeks of screening.

Other

• Subject with Ulcerative Colitis, which is confined to a proctitis (distal 15 cm or less).
• Subject is displaying clinical signs of ischemic colitis, fulminant colitis or toxic megacolon.

• Male and female subject age ≥ 18 and ≤ 75 years of age at screening.
• the body mass index (BMI= weight (kg)/height (2 m ²)) of the subjects is ≥ 18 kg/m ² at the screening.
• Subject has active Ulcerative Colitis with a 9-point modified Mayo score of 4-9 at baseline, with an endoscopic subscore of ≥ 2 (confirmed by central read). (NOTE: endoscopy should be performed within 14 days prior to baseline visit), and rectal bleeding subscore of ≥1.
• Subject has at least a 90-days history of Ulcerative Colitis diagnosis at baseline.
• Subject is deemed by the physician as having inadequate response, loss of response or intolerance (Appendix 5) to at least one conventional treatment (oral 5-ASA, immunosuppressants or corticosteroids), or was previously exposed to anti-TNF therapy (e.g., infliximab, adalimumab) or other biological treatment.
• Subject is capable of providing a signed and dated informed consent form indicating the subject has been informed of all pertinent aspects of the study.
• All women of childbearing potential and their male partners must commit to using at least two methods of contraception with one method being highly effective throughout the duration of the study, and for 72 weeks after last dose of study medication.