This Study Titled an open label, multi-centre, randomized, parallel group, active controlled and comparative phase 3 clinical study to evaluate the efficacy and safety of Upadacitinib Extended Release Tablets 15mg, 30mg, 45mg in Adults with moderately to severely active ulcerative colitis who have had an inadequate response or intolerance to one or more TNF blockers. Initially, subjects will be screened as per predefined eligibility criteria for the study.

Eligible 180 subjects will be enrolled to receive Upadacitinib or Tofacitinib. Subjects will be randomized in a 2:1 ratio. Group 1 will have 120 subjects and Group 2 will have 60 subjects. Group 1 (Treatment group): Upadacitinib Dose: The recommended induction dosage is 45 mg once daily for 8 weeks. The recommended maintenance dosage is 15 mg once daily. A maintenance dosage of 30 mg once daily may be considered for patients with refractory, severe, or extensive disease. Discontinue Upadacitinib if adequate therapeutic response is not achieved with the 30 mg dosage. Use the lowest effective dosage needed to maintain response Group 2 (Control group): Tofacitinib Tablets 5mg, 10mg Dose: 10 mg twice daily for at least 8 weeks; then 5 or 10 mg twice daily. Use the lowest effective dose to maintain response.

 Ulcerative colitis The efficacy and safety of upadacitinib was evaluated in three multicentre, double-blind, placebo-controlled Phase 3 clinical studies: two replicate induction studies, UC-1 (U-ACHIEVE Induction) and UC-2 (U-ACCOMPLISH), and a maintenance study UC-3 (U[1]ACHIEVE Maintenance). Disease activity was based on the adapted Mayo score (aMS, Mayo scoring system excluding Physician’s Global Assessment), which ranged from 0 to 9 and has three subscores that were each scored 0 (normal) to 3 (most severe): stool frequency subscore (SFS), rectal bleeding subscore (RBS) and a centrally-reviewed endoscopy subscore (ES). 

Background information:

Upadacitinib was originally approved for the treatment of rheumatoid arthritis, but its indication has expanded to include ulcerative colitis, ankylosing spondylitis, psoriatic arthritis, Protocol Number: MSN/CT/Upada/2023-2024 M/s. MSN Laboratories Private Limited Version/ Date: 1.2 Dated 12 Feb 2024 Confidential Page 34 of 77 and atopic dermatitis. For all of these indications, the patient must first have failed or been intolerant to anti-TNF therapy; the only exception is atopic dermatitis, as anti-TNFs are not indicated for its treatment. The dosing is generally higher for ulcerative colitis than for other indications: 45 mg daily induction dose for the first 8 weeks, then 30 mg daily. A lower dose of 15 mg (used for all other indications) is recommended in UC for those with renal or hepatic disease. Upadacitinib should be avoided in anyone with cirrhosis due to its hepatic metabolism.

 Safety assessments will include physical & systemic examination, vital signs, ECGs, Laboratory parameters: Blood (hematology & biochemistry) and urinalysis