A Study to Test the Effect of TEV-48574 in Moderate to Severe Ulcerative Colitis or Crohn's Disease

The MMS is a tool designed to measure disease activity for UC. It consisted of 3 subscores: stool frequency, rectal bleeding and endoscopic subscore as determined during central review. Each subscore was graded from 0 (normal) to 3 (severe). These individual subscores were summed up to give a total MMS ranging from 0 (normal or inactive disease) to 9 (severe disease), where higher scores indicated more severe disease activity. Clinical remission was defined as MMS ≤2 points with Mayo stool frequency subscore of 0 or 1, Mayo rectal bleeding subscore of 0, and centrally read endoscopic score of 0 or 1, where a score of 1 did not include "friability".

The SES-CD assessed the degree of inflammation. The SES-CD assesses the following 4 components: presence of ulcers, percentage of ulcerated surfaces, affected surface, and presence of strictures. Each of these components was scored on a scale of 0 (none/unaffected) to 3 (worst). In the SES-CD, each of these 4 components was assessed in the 5 segments: the rectum, sigmoid and left colon, transverse colon, right colon, and ileum. The SES-CD was the sum of the individual scores of each of the components across the 5 segments. The range of SES-CD scores was 0 (none) - 12 (severe) for each segment, and 0 (none) - 60 (severe) for the overall SES-CD score, with larger scores indicating greater degree of inflammation. Endoscopic response at Week 14 in participants with moderate to severe CD was defined as a reduction in SES-CD of at least 50% from baseline.

The MMS is a tool designed to measure disease activity for UC. It consisted of 3 subscores: stool frequency, rectal bleeding and endoscopic subscore as determined during central review. Each subscore was graded from 0 (normal) to 3 (severe). These individual subscores were summed up to give a total MMS ranged from 0 (normal or inactive disease) to 9 (severe disease), where higher scores indicated more severe disease activity. Clinical response was defined as a decrease from baseline in the MMS of at least 2 points and at least a 30% reduction from baseline with either a decrease in rectal bleeding subscore of at least 1 or an absolute rectal bleeding subscore of ≤1.

The endoscopic subscore evaluation for the MMS consisted of independent, blinded, central review of a high-resolution recorded video. The endoscopic subscore assessed disease activity from 0 (normal or inactive disease) to 3 (severe activity). Higher scores indicated more severe disease activity. Endoscopic improvement was defined as a MES of 0 or 1 at Week 14.

The endoscopic subscore evaluation for the MMS consisted of independent, blinded, central review of a high-resolution recorded video. The endoscopic subscore assessed disease activity from 0 (normal or inactive disease) to 3 (severe activity). Higher scores indicated more severe disease activity. Endoscopic remission was defined as a MES of 0 at Week 14.

The PRO2-UC score was derived from 2 parameters from the MMS: stool frequency and rectal bleeding, recorded daily by the participant using a handheld electronic diary over each of the preceding 7 days. Each parameter ranged from 0 (normal) to 3 (severe) with each subscore representing an average over the preceding 7 days. The total score was the summation of the subscores and therefore ranged from 0 (normal or inactive disease) to 6 (severe activity), where higher scores indicated more severe disease activity. Clinical response was defined as decrease from baseline of at least 50% in PRO2 (stool frequency and rectal bleeding) at Week 14.

The PRO2-UC score was derived from 2 parameters from the MMS: stool frequency and rectal bleeding, recorded daily by the participant using a handheld electronic diary over each of the preceding 7 days. Each parameter ranged from 0 (normal) to 3 (severe) with each subscore representing an average over the preceding 7 days. The total score was the summation of the subscores and therefore ranged from 0 (normal or inactive disease) to 6 (severe activity), where higher scores indicated more severe disease activity. Clinical remission was defined as score of stool frequency = 0 and rectal bleeding = 0 on the PRO2 scale at Week 14.

The MM-SES-CD is an endoscopic scoring tool that considers each individual parameter's prognostic value for achieving endoscopic remission while on active therapy. The SES-CD assesses the following 4 components: presence of ulcers, percentage of ulcerated surfaces, affected surface, and presence of strictures. Each of these components was scored on a scale of 0 (none/unaffected) to 3 (worst). In the SES-CD, each of these 4 components was assessed in the 5 segments: the rectum, sigmoid and left colon, transverse colon, right colon, and ileum. The SES-CD was the sum of the individual scores of each of the components across the 5 segments. The range of SES-CD scores was 0 (none) - 12 (severe) for each segment, and 0 (none) - 60 (severe) for the overall SES-CD score, with higher scores indicating a greater degree of inflammation. Endoscopic response was defined as a decrease in MM-SES-CD of ≥50% from baseline at Week 14.

The CDAI score consisted of an adjusted composite sum of 8 parameters, including daily diary evaluation for severity of abdominal pain, general well-being, very soft/liquid stool frequency, extra-intestinal symptoms, need for antidiarrheal drugs, presence of an abdominal mass, body weight, and hematocrit. The subscores of abdominal pain (0 [no pain] to 3 [worst pain]), general well-being (0 [well] to 4 [terrible]), and number of very soft or liquid stools were then summed over the 7 days prior to each visit. Additionally, the remaining predictors were also noted and weighted to create the total CDAI score that ranged from 0 (none) to 600 (severe) with a higher score indicating a worse outcome. Clinical response was defined as a ≥100-point decrease in CDAI score from baseline.

The CDAI score consisted of an adjusted composite sum of 8 parameters, including daily diary evaluation for severity of abdominal pain, general well-being, very soft/liquid stool frequency, extra-intestinal symptoms, need for antidiarrheal drugs, presence of an abdominal mass, body weight, and hematocrit. The subscores of abdominal pain (0 [no pain] to 3 [worst pain]), general well-being (0 [well] to 4 [terrible]), and number of very soft or liquid stools were then summed over the 7 days prior to each visit. Additionally, the remaining predictors were also noted and weighted to create the total CDAI score that ranged from 0 (none) to 600 (severe) with a higher score indicating a worse outcome. Clinical remission was defined as a CDAI score <150 at Week 14.

The PRO2-CD score was the sum of the daily stool frequency subscore (0 [normal] to 3 [severe]) and abdominal pain subscore (0 [no pain] to 3 [worst pain]) from the CDAI. Total PRO2-CD score ranged from 0 (normal) - 6 (severe), with higher scores indicating more severe disease. These were recorded daily by the participant using a handheld electronic diary over each of the preceding 7 days. Clinical response was defined as a decrease from baseline of at least 50% in PRO2-CD (abdominal pain and stool frequency) at Week 14.

The PRO2-CD score was the sum of the daily stool frequency subscore (0 [normal] to 3 [severe]) and abdominal pain subscore (0 [no pain] to 3 [worst pain]) from the CDAI. Total PRO2-CD score ranged from 0 (normal) - 6 (severe), with higher scores indicating more severe disease. These were recorded daily by the participant using a handheld electronic diary over each of the preceding 7 days. Clinical remission was defined as abdominal pain ≤1 and stool frequency ≤3 on the PRO2-CD scale at Week 14

An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AEs were considered TEAEs if onset occurred on or after the first dose date. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

Treatment-emergent ADA positive: - the participant had a positive ADA sample (after first dose of study drug) but not at baseline (prior to first dose of study drug), or - the participant had a positive ADA sample at baseline (prior to first dose of study drug) and at the visit (after first dose of study drug), with at least a 4-fold increase in titer level.

Treatment-emergent ADA positive: - the participant had a positive ADA sample (after first dose of study drug) but not at baseline (prior to first dose of study drug), or - the participant had a positive ADA sample at baseline (prior to first dose of study drug) and at the visit (after first dose of study drug), with at least a 4-fold increase in titer level.