Outcome
| Type |
Measure |
Description |
Time frame |
Safety issue |
| Primary |
Part A: Percentage of Participants Achieving Clinical Remission Based on the Crohn's Disease Activity Index (CDAI) at Week 26 |
Clinical remission is defined as a CDAI score of =150 points. CDAI assesses CD based on clinical signs such as number of liquid or very soft stools, abdominal pain, general wellbeing, extra-intestinal manifestations of CD, antidiarrheal use, presence of abdominal mass, hematocrit and body weight. CDAI consists of eight factors, each summed after adjustment with a weighting factor. Total score ranges from 0 to 600 points. Higher scores indicate more severity. |
Week 26 |
|
| Primary |
Part B: Percentage of Participants in Clinical Remission Based on the CDAI at Week 52 |
Clinical remission is defined as a CDAI score of =150 points. CDAI assesses CD based on clinical signs such as number of liquid or very soft stools, abdominal pain, general wellbeing, extra-intestinal manifestations of CD, antidiarrheal use, presence of abdominal mass, hematocrit and body weight. CDAI consists of eight factors, each summed after adjustment with a weighting factor. Total score ranges from 0 to 600 points. Higher scores indicate more severity. |
Week 52 |
|
| Secondary |
Percentage of Participants Achieving Clinical Remission Based on the CDAI at Week 12 |
Clinical remission is defined as a CDAI score of =150 points. CDAI assesses CD based on clinical signs such as number of liquid or very soft stools, abdominal pain, general wellbeing, extra-intestinal manifestations of CD, antidiarrheal use, presence of abdominal mass, hematocrit and body weight. CDAI consists of eight factors, each summed after adjustment with a weighting factor. Total score ranges from 0 to 600 points. Higher scores indicate more severity. |
Week 12 |
|
| Secondary |
Percentage of Participants Achieving 2-item Patient-reported Outcome Measure (PRO2) Remission at Weeks 12, 26, and 52 |
Clinical remission based on PRO2 is defined as PRO2 score =8 from baseline. The PRO2 is comprised of the stool frequency and abdominal pain components of the CDAI. The PRO-2 score is the sum of the abdominal pain and stool frequency subscores of the CDAI score. The average daily number of liquid or very soft stools and abdominal pain score (with 0 indicating no pain and 3 indicating severe pain) are weighted according to the CDAI multiplication factors (2 for stool frequency and 5 for abdominal pain). A higher score indicates more frequent stools and more severe abdominal pain. |
Weeks 12, 26 and 52 |
|
| Secondary |
Change in PRO2 Score from Week 26 to 52 |
The PRO2 is comprised of the stool frequency and abdominal pain components of the CDAI. The PRO-2 score is the sum of the abdominal pain and stool frequency subscores of the CDAI score. The average daily number of liquid or very soft stools and abdominal pain score (with 0 indicating no pain and 3 indicating severe pain) are weighted according to the CDAI multiplication factors (2 for stool frequency and 5 for abdominal pain). A higher score indicates more frequent stools and more severe abdominal pain. |
Weeks 26 and 52 |
|
| Secondary |
Percentage of Participants with Stool Frequency Remission at Weeks 12, 26, and 52 |
Stool frequency remission is defined as average daily number of liquid or very soft stools =3 and not worse than baseline assessed as per the stool frequency subscore of the CDAI score. The average daily number is weighted according to the CDAI multiplication factor of 2 for stool frequency. A higher score indicates more frequent stools. |
Weeks 12, 26, and 52 |
|
| Secondary |
Percentage of Participants with Abdominal Pain Remission at Weeks 12, 26, and 52 |
Abdominal pain remission is defined as abdominal pain score =1, and not worse than baseline assessed as per the abdominal pain subscore of the CDAI score. The abdominal pain score (with 0 indicating no pain and 3 indicating severe pain) is weighted according to the CDAI multiplication factor of 5. A higher score indicates more severe abdominal pain. |
Weeks 12, 26, and 52 |
|
| Secondary |
Percentage of Participants Achieving Endoscopic Remission Based on Simple Endoscopic Score for Crohn's Disease (SES-CD) at Weeks 26 and 52 |
Endoscopic remission as per SES-CD is defined as SES-CD score from 0-2. SES-CD evaluates 4 endoscopic variables (ulcer size, percentage of surface area (SA) that is ulcerated, percentage of SA affected, and presence and type of narrowings in 5 colonic segments evaluated during ileocolonoscopy. Each variable is coded from 0 to 3 based on severity, where 0 is none or not severe and 3 is most severe case, with sum of scores for each variable ranging from 0 to 15, except for presence of narrowing. Presence of narrowing ranges from 0 to 11 since a severity of 3 represents a narrowing which a colonoscope cannot be passed and, thus, can only be observed once among the bowel segments. The overall SES-CD score ranges from 0 to 56 and is sum of 4 variables across 5 bowel segments. Higher scores indicate more severe disease. Percentage of participants achieving endoscopic remission based on SES-CD at either Week 26 or Week 52 will be reported in this outcome measure. |
Weeks 26 and 52 |
|
| Secondary |
Percentage of Participants Achieving Endoscopic Remission Based on SES-CD at Both Weeks 26 and 52 |
Endoscopic remission as per SES-CD is defined as SES-CD score from 0-2. SES-CD evaluates 4 endoscopic variables (ulcer size, percentage of surface area (SA) that is ulcerated, percentage of SA affected, and presence and type of narrowings in 5 colonic segments evaluated during ileocolonoscopy. Each variable is coded from 0 to 3 based on severity, where 0 is none or not severe and 3 is most severe case, with sum of scores for each variable ranging from 0 to 15, except for presence of narrowing. Presence of narrowing ranges from 0 to 11 since a severity of 3 represents a narrowing which a colonoscope cannot be passed and, thus, can only be observed once among the bowel segments. The overall SES-CD score ranges from 0 to 56 and is sum of 4 variables across 5 bowel segments. Higher scores indicate more severe disease. Percentage of participants achieving endoscopic remission based on SES-CD at both Weeks 26 and 52 will be reported in this outcome measure. |
Weeks 26 and 52 |
|
| Secondary |
Percentage of Participants Exhibiting an Endoscopic Response Based on SES-CD at Weeks 26 and 52 |
Endoscopic response is defined as SES-CD reduction by =50% from Baseline. SES-CD evaluates 4 endoscopic variables (ulcer size, percentage of the surface area that is ulcerated, percentage of the surface area affected, and presence and type of narrowings in 5 colonic segments evaluated during ileocolonoscopy (ileum, right colon, transverse colon, left colon, and rectum). Each variable is coded from 0 to 3 based on severity, where 0 is none or not severe and 3 is the most severe case, with the sum of the scores for each variable ranging from 0 to 15, except for presence of narrowing. Presence of narrowing ranges from 0 to 11 since a severity of 3 represents a narrowing which a colonoscope cannot be passed and, thus, can only be observed once among the bowel segments. The overall SES-CD score ranges from 0 to 56 and is the sum of 4 variables across 5 bowel segments. Higher scores indicate more severe disease. |
Weeks 26 and 52 |
|
| Secondary |
Percentage of Participants in Deep Remission Based on the CDAI and SES-CD at Weeks 26 and 52 |
Deep remission:CDAI <150 points and SES-CD 0-2. CDAI assesses CD per clinical signs such as number of liquid/soft stools,abdominal pain,general wellbeing,extra-intestinal manifestations of CD, antidiarrheal use,presence of abdominal mass, hematocrit and body weight. It has 8 factors each summed after adjustment with weighting factor; total score:0 to 600 points, higher scores=more severity. SES-CD evaluates 4 endoscopic variables(ulcer size, percentage of ulcerated surface area, percentage of affected surface area, and presence and type of narrowings in 5 colonic segments evaluated during ileocolonoscopy. Each variable is coded from 0=none or not severe to 3=most severe case; sum of the scores range from 0 to 15, except for narrowing. Presence of narrowing ranges from 0 to 11. Overall SES-CD score ranges from 0 to 56 and is the sum of 4 variables. Higher scores=more severe disease. Participants achieving deep remission at either Week 26 or 52 will be assessed in this outcome measure. |
Weeks 26 and 52 |
|
| Secondary |
Percentage of Participants in Deep Remission Based on the CDAI and SES-CD at Both Weeks 26 and 52 |
Deep remission:CDAI <150 points and SES-CD 0-2. CDAI assesses CD per clinical signs such as number of liquid/soft stools,abdominal pain,general wellbeing,extra-intestinal manifestations of CD, antidiarrheal use,presence of abdominal mass, hematocrit and body weight. It has 8 factors each summed after adjustment with weighting factor; total score:0 to 600 points, higher scores=more severity. SES-CD evaluates 4 endoscopic variables(ulcer size, percentage of ulcerated surface area, percentage of affected surface area, and presence and type of narrowings in 5 colonic segments evaluated during ileocolonoscopy. Each variable is coded from 0=none or not severe to 3=most severe case; sum of the scores range from 0 to 15, except for narrowing. Presence of narrowing ranges from 0 to 11. Overall SES-CD score ranges from 0 to 56 and is the sum of 4 variables. Higher scores=more severe disease. Participants achieving deep remission at both Weeks 26 and 52 will be assessed in this outcome measure. |
Weeks 26 and 52 |
|
| Secondary |
Percentage of Participants Exhibiting a Clinical Response Based on the CDAI at Weeks 12, 26, and 52 |
Clinical response is defined as =100-point decrease from Baseline in CDAI score. CDAI assesses CD based on clinical signs such as number of liquid or very soft stools, abdominal pain, general wellbeing, extra-intestinal manifestations of CD, antidiarrheal use, presence of abdominal mass, hematocrit and body weight. CDAI consist of eight factors, each summed after adjustment with a weighting factor. Total score ranges from 0 to 600 points. Higher scores indicate more severity. |
Weeks 12, 26, and 52 |
|
| Secondary |
Percentage of Participants Using Oral Corticosteroids at Baseline who have Discontinued Corticosteroids and are in Clinical Remission Based on the CDAI |
Percentage of participants using oral corticosteroids at Baseline who have discontinued corticosteroids and are in clinical remission per CDAI will be reported. Clinical remission is defined as a CDAI score of =150 points. CDAI assesses CD based on clinical signs such as number of liquid or very soft stools, abdominal pain, general wellbeing, extra-intestinal manifestations of CD, antidiarrheal use, presence of abdominal mass, hematocrit and body weight. CDAI consist of eight factors, each summed after adjustment with a weighting factor. Total score ranges from 0 to 600 points. Higher scores indicate more severity. |
Week 30 through Week 64 |
|
| Secondary |
Percentage of Participants Achieving Complete Endoscopic Healing Based on SES-CD at Weeks 26 and 52 |
Complete endoscopic healing is defined as SES-CD score =4 with a =2-point decrease from baseline and no individual subscore >1. SES-CD evaluates 4 endoscopic variables (ulcer size, percentage of the surface area that is ulcerated, percentage of the surface area affected, and presence and type of narrowings in 5 colonic segments evaluated during ileocolonoscopy (ileum, right colon, transverse colon, left colon, and rectum). Each variable is coded from 0 to 3 based on severity, where 0 is none or not severe and 3 is the most severe case, with the sum of the scores for each variable ranging from 0 to 15, except for presence of narrowing. Presence of narrowing ranges from 0 to 11 since a severity of 3 represents a narrowing which a colonoscope cannot be passed and, thus, can only be observed once among the bowel segments. The overall SES-CD score ranges from 0 to 56 and is the sum of 4 variables across 5 bowel segments. Higher scores indicate more severe disease. |
Weeks 26 and 52 |
|
| Secondary |
Change in SES-CD from Baseline to Weeks 26 and 52 |
SES-CD evaluates 4 endoscopic variables (ulcer size, percentage of the surface area that is ulcerated, percentage of the surface area affected, and presence and type of narrowings in 5 colonic segments evaluated during ileocolonoscopy (ileum, right colon, transverse colon, left colon, and rectum). Each variable is coded from 0 to 3 based on severity, where 0 is none or not severe and 3 is the most severe case, with the sum of the scores for each variable ranging from 0 to 15, except for presence of narrowing. Presence of narrowing ranges from 0 to 11 since a severity of 3 represents a narrowing which a colonoscope cannot be passed and, thus, can only be observed once among the bowel segments. The overall SES-CD score ranges from 0 to 56 and is the sum of 4 variables across 5 bowel segments. Higher scores indicate more severe disease. |
Baseline, Weeks 26 and 52 |
|
| Secondary |
Percentage of Participants with First CD Exacerbation After 26 Weeks |
CD exacerbation is defined as a >70-point increase in CDAI from the prior visit on 2 occasions separated by a 2-week interval, and either CRP above normal or fecal calprotectin [FCP] >250 micrograms per gram (µg/g). CDAI assesses CD based on clinical signs such as number of liquid or very soft stools, abdominal pain, general wellbeing, extra-intestinal manifestations of CD, antidiarrheal use, presence of abdominal mass, hematocrit and body weight. CDAI consist of eight factors, each summed after adjustment with a weighting factor. Total score ranges from 0 to 600 points. Higher scores indicate more severity. |
Week 26 through Week 52 |
|
| Secondary |
Change in FCP Concentrations from Baseline to Weeks 12, 26, 42, and 52 |
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Baseline, Weeks 12, 26, 42, and 52 |
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