A phase 3 Study to Evaluate the Efficacy and Safety of SHR0302 in Ulcerative Colitis

INTERVENTION: Product Name: SHR0302 tablets Product Code: SHR0302 Pharmaceutical Form: Film‐coated tablet INN or Proposed INN: SHR0302 CAS Number: 1639419‐51‐4 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 4‐ Pharmaceutical form of the placebo: Film‐coated tablet Route of administration of the placebo: Oral use CONDITION: Moderately to severely active Ulcerative Colitis (UC) ; MedDRA version: 20.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 100000004856 Therapeutic area: Diseases [C] ‐ Digestive System Diseases [C06] PRIMARY OUTCOME: Main Objective: Part 1 Induction phase: to evaluate the efficacy of SHR0302 8 mg QD, compared to placebo in inducing clinical remission in adult subjects with moderately to severely active ulcerative colitis at week 8. ; Part 2 Maintenance phase: to evaluate the efficacy of SHR0302 4 mg QD compared to placebo as maintenance treatment in maintaining clinical remission in adult subjects with moderately to severely active ulcerative colitis at week 52. ; Part 3 Open‐Label Extension phase: to evaluate the long‐term safety of SHR0302 4 mg QD in adult subjects with moderately to severely active ulcerative colitis; Primary end point(s): ‐ Part 1 Induction phase; Percentage of subjects in clinical remission at week 8. ; ‐ Part 2 Maintenance phase; Percentage of subjects in clinical remission at week 52; Secondary Objective: Part 1 ; To evaluate the efficacy of SHR0302 in achieving endoscopic remission in subjects with moderately to severely active ulcerative colitis (UC).; To evaluate the efficacy of SHR0302 as induction therapy on clinical response in subjects with moderately to severely active UC.; To characterize the PK of SHR0302 in moderately to severely active UC and explore the correlation of exposure‐response.; To evaluate the safety and tolerability of SHR0302 in subjects with moderately to severely active UC.; Part 2 ; To evaluate the efficacy of SHR0302 in endoscopic remission in subjects with moderately to severely active UC.; To evaluate the efficacy of SHR0302 as maintenance therapy on clinical response in subjects with moderately to severely active UC.; To evaluate the safety and tolerability of SHR0302 in subjects with moderately to severely active UC. ; Part 3 ; To evaluate the efficacy of SHR0302 in Partial Mayo score remission in subjects with moderately to severely active UC.; Timepoint(s) of evaluation of this end point: ‐ Part 1 Induction phase at week 8. ; ‐ Part 2 Maintenance phase at week 52 SECONDARY OUTCOME: Secondary end point(s): Part 1; ‐ The percentage of subjects with endoscopic remission.; ‐ The percentage of subjects with clinical response.; ‐ Change from baseline in partial Mayo score.; ‐ Change in total Mayo score and 9‐point modified Mayo score.; Part 2; ‐ The percentage of subjects with endoscopic remission.; ‐ The percentage of subjects with clinical response.; ‐ Change from baseline in partial Mayo score.; ‐ Change in total Mayo score and 9‐point modified Mayo score.; ‐ Percentage of subjects in corticosteroid‐free remission. Corticosteroid‐free is defined as the subjects who discontinue corticosteroid of at least 4 weeks prior to the visit.; ‐ Percentage of subjects who maintain clinical remission.; Part 3; ‐ The percentage of subjects in clinical remission per partial Mayo score. Defined as: total Partial Mayo score = 1.; ‐ The percentage of subjects in corticosteroid‐free remission per Partial Mayo score.; ‐ Change from baseline in Partial Mayo score. Timepoint(s) of evaluation of this end point: Part 1; ‐ at week 8.; ‐ at week 8.; ‐ at week 2, 4, and 8.; ‐ at week 8.; Part 2; ‐ at week 52.; ‐ at week 52.; ‐ at week 12, 16, 24, 32, 40, and 52.; ‐ at week 52.; ‐ at week 52, corticosteroid‐free is defined as the subjects who discontinue corticosteroid of at least 4 weeks prior to the visit.; ‐ at week 52.; Part 3; ‐ at week E26. ; ‐ at week E26.; ‐ at week E2, E12, and E26. INCLUSION CRITERIA: Inclusion Criteria for Part 1 Induction phase 1. Male and female subjects age =18 and =75 years of age at baseline. 2. Subject has active ulcerative colitis with a 9‐point modified Mayo score of =5, with an endoscopic subscore of =2 (confirmed by central read) prior to 14 days of baseline visit. (Note: endoscopy should be performed within 14 days prior to baseline visit). 3. Subject has at least a three‐month history of ulcerative colitis diagnosis at baseline. 4. Subject is deemed by the investigator as having an inadequate response, loss of response or intolerance (see 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 (e.g., vedolizumab) having discontinued the treatment for: ‐ Infliximab: a minimum of 8 weeks prior to baseline. ‐ Adalimumab: a minimum of 10 weeks prior to baseli