A study comparing two different therapeutic approaches in the treatment of moderate to severe ulcerative colitis

INTERVENTION: Trade Name: Amgevita Pharmaceutical Form: Solution for injection in pre‐filled syringe INN or Proposed INN: Adalimumab 40mg CAS Number: 331731‐18‐1 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 40‐mg Trade Name: Azathioprine Pharmaceutical Form: Film‐coated tablet Other descriptive name: AZATHIOPRINE BP Concentration unit: mg/kg milligram(s)/kilogram Concentration type: equal Concentration number: 2‐2.5 CONDITION: Moderate to severe ulcerative colitis ; 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: The primary objective is to assess the efficacy of a top‐down; approach in achieving histological improvement at week 52,; without colectomy and without UC‐related hospitalization versus; a standard step‐up approach. Primary end point(s): Histological improvement (defined as a Nancy index = 1) at week 52, without colectomy and without UC‐related hospitalization. Secondary Objective: Secondary objectives will be:; ‐ to compare the efficacy of the top‐down approach to; induce histological remission and histological healing in the; short‐term (week 16) vs. the standard step‐up approach; ‐ to compare the efficacy of the top‐down approach to; induce clinical remission (combined clinical and endoscopic; improvement=sub‐score of 0 or 1) in the short‐ and long‐term; (week 16 and week 52) vs. the standard step‐up approach; ‐ to compare the efficacy of the top‐down approach to; induce short‐ and long‐term mucosal healing (endoscopic and; histologic improvement) vs. the standard step‐up approach; ‐ to compare the safety of the top‐down approach through; week 52 vs. the standard step‐up approach; ‐ to compare the quality of life of patients treated with the; top‐down approach through week 52 vs. the standard step‐up; approach; ‐ To compare the need for colectomies and UC‐related; hospitalizations in patients treated with the top‐down approach; vs. the step‐up approach. Timepoint(s) of evaluation of this end point: Week 52 SECONDARY OUTCOME: Secondary end point(s): ‐ Histological remission (Nancy Index =0) at week 16; ‐ Histological remission (Nancy Index =0) at week 52; ‐ Histological healing (defined as a Nancy score = 1) at week 16; ‐ Clinical remission (PRO2 remission + endoscopic remission) at week 52; ‐ Clinical remission (PRO2+endoscopic remission) at week 16; ‐ Symptomatic remission (PRO2 remission) at week 16; ‐ Symptomatic remission (PRO2 remission) at week 52; ‐ Endoscopic improvement at week 16 ; Endoscopic improvement at week 52; ‐ Endoscopic remission at week 16; ‐ Endoscopic remission at week 52; ‐ Mucosal healing (endoscopic and histologic improvement) at week 16; ‐ Mucosal healing (endoscopic and histologic improvement) at week 52; ‐ Changes in fecal calprotectin levels from baseline; ‐ Need for corticosteroids at weeks 16 and 52; ‐ To evaluate and compare the safety of the two strategies in terms of adverse events,; serious adverse events, and adverse events leading to discontinuation; ‐ quality of life (measured by the S‐IBDQ and SF‐36) at weeks 16 and 52; ‐ Rates of colectomies at weeks 16, 52, and 104 (or end of study); ‐ UC‐related hospitalizations at weeks 16, 52, and 104 (or end of study) Timepoint(s) of evaluation of this end point: Weekd 16 and/or week 52, depending on the endpoints INCLUSION CRITERIA: ‐ Adult patients (age = 18 years and < 75 years) ‐ Established diagnosis of UC (confirmed clinically, endoscopically and histologically) since at least 3 months ‐ Disease duration no longer than 24 months before the screening visit ‐ Ongoing oral 5‐ASA treatment =1.6g/day ‐ Having objective signs of moderate‐to‐severe UC activity, defined by a total Mayo score of 6 to 12. ‐ Proctitis, left‐sided or extensive UC ‐ Ability to perform study requirements ‐ Ability to give informed consent according to ICH/ GCP, and national/local regulations. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 250 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 100