A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of ABT-494 for the Induction of Symptomatic and Endoscopic Remission in Subjects With Moderately to Severely Active Crohn's Disease Who Have Inadequately Responded to or Are Intolerant to Immunomodulators or Anti-TNF Therapy

Study Overview
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Brief Summary
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To determine the efficacy and safety of multiple doses of ABT-494 in subjects with moderately to severely active Crohn's Disease with a history of inadequate response to or intolerance to Immunomodulators or anti-Tumor Necrosis Factor (TNF) therapy.

Official Title
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A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of Upadacitinib (ABT-494) for the Induction of Symptomatic and Endoscopic Remission in Subjects With Moderately to Severely Active Crohn's Disease Who Have Inadequately Responded to or Are Intolerant to Immunomodulators or Anti-TNF Therapy

Conditions
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Crohn's Disease

Intervention / Treatment
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* Drug: Placebo
* Drug: ABT-494


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of Crohn's disease (CD) for at least 90 days. Crohn's Disease Activity Index (CDAI) greater than or equal to 220 and less than or equal to 450. Subject inadequately responded to or experienced intolerance to previous treatment with immunomodulators (e.g. azathioprine, 6-mercaptopurine, or methotrexate) and/or anti-TNF agent (e.g., infliximab, adalimumab, or certolizumab pegol). Exclusion Criteria: Subjects with ulcerative colitis (UC), collagenous colitis or indeterminate colitis. Subject who has had surgical bowel resections in the past 6 months or is planning resection. Subjects with an ostomy or ileoanal pouch. Subject with symptomatic bowel stricture or abdominal or peri-anal abcess. Subject who has short bowel syndrome. Subject with recurring infections or active Tuberculosis (TB).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Induction Period ABT-494 Twice Daily Medium/High Dose<br>Induction Period ABT-494 Twice Daily Medium/High Dose orally dosed twice a day | Drug: ABT-494<br>* Oral Dosing<br>* Other names: Upadacitinib;|
| Active Comparator: Extension Phase ABT-494 High Dose<br>Extension Phase ABT-494 High Dose orally dosed twice a day | Drug: ABT-494<br>* Oral Dosing<br>* Other names: Upadacitinib;|
| Placebo Comparator: Induction Period Placebo<br>Induction Period Placebo orally dosed twice a day | Drug: Placebo<br>* Oral Dosing<br>|
| Active Comparator: Induction Period ABT-494 Low Dose<br>Induction Period ABT-494 Low Dose orally dosed twice a day | Drug: ABT-494<br>* Oral Dosing<br>* Other names: Upadacitinib;|
| Active Comparator: Induction Period ABT-494 Once Daily Medium/High Dose<br>Induction Period ABT-494 Once Daily Medium/High Dose orally dosed once a day | Drug: ABT-494<br>* Oral Dosing<br>* Other names: Upadacitinib;|
| Active Comparator: Extension Phase ABT-494 Low Dose<br>Extension Phase ABT-494 Low Dose orally dosed twice a day | Drug: ABT-494<br>* Oral Dosing<br>* Other names: Upadacitinib;|
| Active Comparator: Induction Period ABT-494 High Dose<br>Induction Period ABT-494 High Dose orally dosed twice a day | Drug: ABT-494<br>* Oral Dosing<br>* Other names: Upadacitinib;|
| Active Comparator: Induction Period ABT-494 Low/Medium Dose<br>Induction Period ABT-494 Low/Medium Dose orally dosed twice a day | Drug: ABT-494<br>* Oral Dosing<br>* Other names: Upadacitinib;|
| Active Comparator: Extension Phase ABT-494 Medium Dose<br>Extension Phase ABT-494 Medium Dose orally dosed twice a day | Drug: ABT-494<br>* Oral Dosing<br>* Other names: Upadacitinib;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieve Endoscopic Remission at Week 12/16 | Endoscopic remission was determined using Simplified Endoscopic Score for Crohn's Disease (SES-CD). SES-CD subscores assess the following: presence and size of ulcers in 5 visualized bowel segments; extent of ulcerated surface in 5 visualized bowel segments; extent of affected surface in 5 visualized bowel segments; presence and type of narrowings in 5 visualized bowel segments. Subscores range from 0 to 15, and are summed for a total SES-CD score ranging from 0 to 56; higher scores indicate greater severity of mucosal inflammation. Endoscopic remission: SES-CD ≤ 4 and at least 2-point reduction versus Baseline and no subscore > 1 in any individual variable. | Up to Week 16. (At Baseline, participants were allocated by randomization 1:1 to have their end of induction colonoscopy done at either Week 12 or Week 16; this endpoint combines the two time points.) | 
| Percentage of Participants Who Achieve Clinical Remission at Week 16 | Clinical remission: average daily stool frequency ≤ 1.5 and not worse than Baseline AND average daily abdominal pain ≤ 1.0 and not worse than Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). | Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieve Crohn's Disease Activity Index (CDAI) < 150 at Week 16 | CDAI is used to quantify the signs and symptoms of subjects with Crohn's disease. The score includes the frequency of stools, abdominal pain and general well-being as well as the presence of complications, use of antidiarrheals, presence of abdominal mass, hematocrit and weight. CDAI generally ranges from 0 to 600 where higher scores indicate more severe disease. A score below 150 indicates remission. | Week 16 | 
| Percentage of Participants With a Decrease in CDAI ≥ 70 Points From Baseline at Week 16 | CDAI is used to quantify the signs and symptoms of subjects with Crohn's disease. The score includes the frequency of stools, abdominal pain and general well-being as well as the presence of complications, use of antidiarrheals, presence of abdominal mass, hematocrit and weight. CDAI generally ranges from 0 to 600 where higher scores indicate more severe disease. A 70-point decrease in the CDAI index refers to improvement in the disease activity from Baseline. | Week 16 | 
| Percentage of Participants Who Achieve Clinical Remission at Week 12 | Clinical remission: average daily stool frequency ≤ 1.5 and not worse than Baseline AND average daily abdominal pain ≤ 1.0 and not worse than Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). | Week 12 | 
| Percentage of Participants Who Achieve Remission at Week 16 | Remission is defined as endoscopic remission at Week 12/16 AND clinical remission at Week 16. Endoscopic remission: SES-CD ≤ 4 and at least 2-point reduction versus Baseline and no subscore > 1 in any individual variable. Clinical remission: average daily stool frequency ≤ 1.5 and not worse than Baseline AND average daily abdominal pain ≤ 1.0 and not worse than Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). Details of the SES-CD scale are provided in the description of the first primary endpoint. | Week 16 | 
| Percentage of Participants Who Achieve Response at Week 16 | Response is defined as endoscopic response at Week 12/16 AND clinical response at Week 16. Endoscopic response: SES-CD at least 25% reduction from Baseline. Clinical response: average daily stool frequency at least 30% reduction from Baseline and average daily abdominal pain not worse than Baseline OR average daily abdominal pain at least 30% reduction from Baseline and average daily stool frequency not worse than Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). Details of the SES-CD scale are provided in the description of the first primary endpoint. | Week 16 | 
| Percentage of Participants With Endoscopic Response at Week 12/16 | Endoscopic response: SES-CD at least 25% reduction from Baseline. Details of the SES-CD scale are provided in the description of the first primary endpoint. | Up to Week 16 (At Baseline, participants were allocated by randomization 1:1 to have their end of induction colonoscopy done at either Week 12 or Week 16; this endpoint combines the two time points.) | 
| Percentage of Participants Who Achieve Clinical Response at Week 16 | Clinical response: average daily stool frequency at least 30% reduction from Baseline and average daily abdominal pain not worse than Baseline OR average daily abdominal pain at least 30% reduction from Baseline and average daily stool frequency not worse than Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). | Week 16 | 
| Percentage of Participants With an Average Daily Stool Frequency ≥ 2.5 AND Average Daily Abdominal Pain ≥ 2.0 at Baseline Who Achieve Clinical Remission at Week 16 | Clinical remission: average daily stool frequency ≤ 1.5 and not worse than Baseline AND average daily abdominal pain ≤ 1.0 and not worse than Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). | Week 16 | 
| Percentage of Participants Taking Corticosteroids at Baseline Who Discontinued Corticosteroid Use and Achieve CDAI < 150 at Week 16 | CDAI is used to quantify the signs and symptoms of subjects with Crohn's disease. The score includes the frequency of stools, abdominal pain and general well-being as well as the presence of complications, use of antidiarrheals, presence of abdominal mass, hematocrit and weight. CDAI generally ranges from 0 to 600 where higher scores indicate more severe disease. A score below 150 indicates remission. | Week 16 | 
| Percentage of Participants Taking Corticosteroids at Baseline Who Discontinued Corticosteroid Use and Achieve Remission at Week 12/16 and Clinical Remission at Week 16 | Remission is defined as endoscopic remission at Week 12/16 AND clinical remission at Week 16. Endoscopic remission: SES-CD ≤ 4 and at least 2-point reduction versus Baseline and no subscore > 1 in any individual variable. Clinical remission: average daily stool frequency ≤ 1.5 and not worse than Baseline AND average daily abdominal pain ≤ 1.0 and not worse than Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). Details of the SES-CD scale are provided in the description of the first primary endpoint. | Up to Week 16. (At Baseline, subjects were allocated by randomization 1:1 to have their end of induction colonoscopy done at either Week 12 or Week 16; this endpoint combines the two time points.) | 
| Percentage of Participants Taking Corticosteroids at Baseline Who Discontinued Corticosteroid Use and Achieve Clinical Remission at Week 16 | Clinical remission: average daily stool frequency ≤ 1.5 and not worse than Baseline AND average daily abdominal pain ≤ 1.0 and not worse than Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). | Week 16 | 
| Percentage of Participants Taking Corticosteroids at Baseline Who Discontinued Corticosteroid Use and Achieve Endoscopic Remission at Week 12/16 | Endoscopic remission: SES-CD ≤ 4 and at least 2-point reduction versus Baseline and no subscore > 1 in any individual variable. Details of the SES-CD scale are provided in the description of the first primary endpoint. | Up to Week 16. (At Baseline, participants were allocated by randomization 1:1 to have their end of induction colonoscopy done at either Week 12 or Week 16; this endpoint combines the two time points.) | 
| Change From Baseline in Fecal Calprotectin Level Over Time During the Induction Phase |  | Baseline, Week 4, Week 16 | 
| Change From Baseline in High-Sensitivity C-Reactive Protein (Hs-CRP) at Week 16 |  | Baseline, Week 16 | 
| Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Over Time During the Induction Phase | The IBDQ is a disease-specific instrument composed of 32 Likert-scaled items. The total score ranges from 32 to 224 using the 7-point response options, with higher scores indicating better health-related quality of life. | Baseline, Week 8, Week 16 | 
| Percentage of Participants With Isolated Ileal Crohn's Disease at Baseline Who Achieve Remission at Week 16 | Remission is defined as endoscopic remission AND clinical remission. Endoscopic remission: SES-CD ≤ 4 and at least 2-point reduction versus Baseline and no subscore > 1 in any individual variable. Clinical remission: average daily stool frequency ≤ 1.5 and not worse than Baseline AND average daily abdominal pain ≤ 1.0 and not worse than Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). Details of the SES-CD scale are provided in the description of the first primary endpoint. | Week 16 | 
| Percentage of Participants With a Decrease in CDAI ≥ 100 Points From Baseline at Week 16 | CDAI is used to quantify the signs and symptoms of subjects with Crohn's disease. The score includes the frequency of stools, abdominal pain and general well-being as well as the presence of complications, use of antidiarrheals, presence of abdominal mass, hematocrit and weight. CDAI generally ranges from 0 to 600 where higher scores indicate more severe disease. A score below 150 indicates remission and a score above 450 indicates very severe disease. | Week 16 | 
| Percentage of Participants Who Achieve > 50% Reduction From Baseline in SES-CD or Endoscopic Remission at Week 12/16 | Endoscopic remission: SES-CD ≤ 4 and at least two point reduction versus Baseline and no subscore > 1 in any individual variable. Details of the SES-CD scale are provided in the description of the first primary endpoint. | Up to Week 16. (At Baseline, participants were allocated by randomization 1:1 to have their end of induction colonoscopy done at either Week 12 or Week 16; this endpoint combines the two time points.) | 
| Percentage of Participants Who Achieve Modified Clinical Remission at Week 16 Among Participants With an Average Daily Stool Frequency ≥ 4.0 or Average Daily Abdominal Pain ≥ 2.0 at Baseline | Modified clinical remission was defined as average daily stool frequency <= 2.8 and not worse than Baseline and average daily abdominal pain <= 1.0 and not worse than Induction Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). | Week 16 | 
| Change From Baseline in Abdominal Pain Rating Scale at Week 12 | Abdominal pain was assessed on an abdominal pain rating scale, where subjects rated their average abdominal pain over the last 24 hours on a scale of 0 (none) to 10 (worst pain imaginable). | Baseline, Week 12 | 
| Change From Baseline in Abdominal Pain Rating Scale at Week 16 | Abdominal pain was assessed on an abdominal pain rating scale, where subjects rated their average abdominal pain over the last 24 hours on a scale of 0 (none) to 10 (worst pain imaginable). | Baseline, Week 16 | 
| Percentage of Participants Who Achieve Remission at Week 52 | Remission at Week 52 was defined as both endoscopic remission at Week 52 and clinical remission at Week 52. Endoscopic remission: SES-CD ≤ 4 and at least 2-point reduction versus Baseline and no subscore > 1 in any individual variable. Clinical remission: average daily stool frequency ≤ 1.5 and not worse than Baseline AND average daily abdominal pain ≤ 1.0 and not worse than Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). See SES-CD description details in the first primary endpoint description of this record. See definitions of responder and clinical responder in Outcome Measure 7 of this record. | Week 52 | 
| Percentage of Participants Who Achieve Endoscopic Remission at Week 52 | Endoscopic remission: SES-CD ≤ 4 and at least 2-point reduction versus Baseline and no subscore > 1 in any individual variable. Details of the SES-CD scale are provided in the description of the first primary endpoint. | Week 52 | 
| Percentage of Participants Who Achieve Both Endoscopic Remission and Modified Clinical Remission at Week 52 Among Subjects With Daily Stool Frequency ≥ 4.0 or Daily Abdominal Pain ≥ 2.0 at Induction Baseline | Endoscopic remission was defined as SES-CD <= 4 and at least 2 points reduction versus induction baseline and no subscore > 1 in any individual variable. Modified clinical remission was defined as average daily stool frequency <= 2.8 and not worse than induction baseline AND average daily abdominal pain <= 1.0 and not worse than induction baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). See SES-CD description details in the first primary endpoint description of this record. | Week 52 | 
| Percentage of Participants Who Achieve Clinical Remission Over Time During Extension Phase in Participants Receiving Upadacitinib in Induction | Clinical remission was defined as average daily stool frequency <= 1.5 and not worse than Induction Baseline and average daily abdominal pain <= 1.0 and not worse than Induction Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). | Week 20, Week 28, Week 36, Week 44, Week 52 | 
| Percentage of Participants Who Maintain Clinical Remission Over Time Among Participants in Clinical Remission at Week 16 in Participants Receiving Upadacitinib in Induction | Clinical remission was defined as average daily stool frequency <= 1.5 and not worse than Induction Baseline and average daily abdominal pain <= 1.0 and not worse than Induction Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). | Week 20, Week 28, Week 36, Week 44, Week 52 | 
| Percentage of Participants Who Achieve Modified Clinical Remission Over Time During Extension Phase Among Participants With Daily Stool Frequency ≥ 4.0 or Daily Abdominal Pain ≥ 2.0 at Induction Baseline | Modified clinical remission was defined as average daily stool frequency <= 2.8 and not worse than Induction Baseline and average daily abdominal pain <= 1.0 and not worse than Induction Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). | Week 20, Week 28, Week 36, Week 44, Week 52 | 
| Percentage of Participants Who Achieve Modified Clinical Remission Over Time During Extension Phase Among Participants In Modified Clinical Remission At Week 16 and Daily Stool Frequency ≥ 4.0 or Daily Abdominal Pain ≥ 2.0 at Induction Baseline | Modified clinical remission was defined as average daily stool frequency <= 2.8 and not worse than Induction Baseline and average daily abdominal pain <= 1.0 and not worse than Induction Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). | Week 20, Week 28, Week 36, Week 44, Week 52 | 
| Percentage of Participants Who Achieve Response at Week 52 | Response at Week 52 was defined as both endoscopic response at Week 52 and clinical response at Week 52. Endoscopic response: SES-CD at least 25% reduction from Baseline. Clinical response: average daily stool frequency at least 30% reduction from Induction Baseline and average daily abdominal pain not worse than Induction Baseline OR average daily abdominal pain at least 30% reduction from Induction Baseline and average daily stool frequency not worse than Induction Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). Details of the SES-CD scale are provided in the description of the first primary endpoint. | Week 52 | 
| Percentage of Participants With SES-CD ≤ 2 at Week 52 | SES-CD subscores assess the following: presence and size of ulcers in 5 visualized bowel segments; extent of ulcerated surface in 5 visualized bowel segments; extent of affected surface in 5 visualized bowel segments; presence and type of narrowings in 5 visualized bowel segments. Subscores range from 0 to 15, and are summed for a total SES-CD score ranging from 0 to 56; higher scores indicate greater severity of mucosal inflammation. | Week 52 | 
| Percentage of Participants With SES-CD = 0 at Week 52 | SES-CD subscores assess the following: presence and size of ulcers in 5 visualized bowel segments; extent of ulcerated surface in 5 visualized bowel segments; extent of affected surface in 5 visualized bowel segments; presence and type of narrowings in 5 visualized bowel segments. Subscores range from 0 to 15, and are summed for a total SES-CD score ranging from 0 to 56; higher scores indicate greater severity of mucosal inflammation. | Week 52 | 
| Percentage of Participants Who Achieve Endoscopic Response at Week 52 | Endoscopic response was defined as SES-CD at least 25% reduction from Induction Baseline. SES-CD subscores assess the following: presence and size of ulcers in 5 visualized bowel segments; extent of ulcerated surface in 5 visualized bowel segments; extent of affected surface in 5 visualized bowel segments; presence and type of narrowings in 5 visualized bowel segments. Subscores range from 0 to 15, and are summed for a total SES-CD score ranging from 0 to 56; higher scores indicate greater severity of mucosal inflammation. | Week 52 | 
| Percentage of Participants Who Achieve Enhanced Endoscopic Response at Week 52 | Enhanced endoscopic response was defined as SES-CD reduction from Induction Baseline > 50% (or for an Induction Baseline SES-CD of 4, at least a 2 point reduction from Induction Baseline). SES-CD subscores assess the following: presence and size of ulcers in 5 visualized bowel segments; extent of ulcerated surface in 5 visualized bowel segments; extent of affected surface in 5 visualized bowel segments; presence and type of narrowings in 5 visualized bowel segments. Subscores range from 0 to 15, and are summed for a total SES-CD score ranging from 0 to 56; higher scores indicate greater severity of mucosal inflammation. | Week 52 | 
| Percentage of Participants Who Achieve Endoscopic Improvement at Week 52 | Endoscopic Improvement: SES-CD reduction from Induction Baseline > 50% or endoscopic remission. Endoscopic remission was defined as SES-CD <= 4 and at least 2 points reduction versus Induction Baseline and no subscore > 1 in any individual variable. SES-CD subscores assess the following: presence and size of ulcers in 5 visualized bowel segments; extent of ulcerated surface in 5 visualized bowel segments; extent of affected surface in 5 visualized bowel segments; presence and type of narrowings in 5 visualized bowel segments. Subscores range from 0 to 15, and are summed for a total SES-CD score ranging from 0 to 56; higher scores indicate greater severity of mucosal inflammation. | Week 52 | 
| Percentage of Participants Who Achieve Endoscopic Healing at Week 52 | Endoscopic healing was defined as SES-CD ulcerated surface subscore of 0 in subjects with SES-CD ulcerated surface subscore >= 1 at Induction Baseline. SES-CD subscores assess the following: presence and size of ulcers in 5 visualized bowel segments; extent of ulcerated surface in 5 visualized bowel segments; extent of affected surface in 5 visualized bowel segments; presence and type of narrowings in 5 visualized bowel segments. Subscores range from 0 to 15, and are summed for a total SES-CD score ranging from 0 to 56; higher scores indicate greater severity of mucosal inflammation. | Week 52 | 
| Percentage of Participants Who Achieve Clinical Response Over Time During Extension Phase | Clinical response was defined as average daily stool frequency at least 30% reduction from Induction Baseline and average daily abdominal pain not worse than Induction Baseline OR average daily abdominal pain at least 30% reduction from Induction Baseline and average daily stool frequency not worse than Induction Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). | Week 20, Week 28, Week 36, Week 44, Week 52 | 
| Percentage of Participants Who Achieve Enhanced Clinical Response Over Time During Extension Phase | Enhanced clinical response was defined as average daily stool frequency at least 60% reduction from Induction Baseline and average daily abdominal pain not worse than Induction Baseline OR average daily abdominal pain at least 35% reduction from Induction Baseline and average daily stool frequency not worse than Induction Baseline or modified clinical remission (average daily stool frequency ≤ 2.8 and not worse than Induction baseline AND average daily abdominal pain ≤ 1.0 and not worse than Induction baseline). The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). | Week 20, Week 28, Week 36, Week 44, Week 52 | 
| Percentage of Participants Who Achieve Enhanced Clinical Response Over Time During Extension Phase Among Participants In Enhanced Clinical Response At Week 16 | Enhanced clinical response was defined as average daily stool frequency at least 60% reduction from Induction Baseline and average daily abdominal pain not worse than Induction Baseline or average daily abdominal pain at least 35% reduction from Induction Baseline and average daily stool frequency not worse than Induction Baseline or modified clinical remission (average daily stool frequency ≤ 2.8 and not worse than Induction baseline AND average daily abdominal pain ≤ 1.0 and not worse than Induction baseline). The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). | Week 20, Week 28, Week 36, Week 44, Week 52 | 
| Percentage of Participants Who Achieve Clinical Remission Over Time During Extension Phase Among Participants With an Average Daily Stool Frequency ≥ 2.5 and Average Daily Abdominal Pain ≥ 2.0 at Induction Baseline | Clinical remission was defined as average daily stool frequency <= 1.5 and not worse than Induction Baseline AND average daily abdominal pain <= 1.0 and not worse than Induction Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). | Week 20, Week 28, Week 36, Week 44, Week 52 | 
| Percentage of Participants Taking Corticosteroids at Induction Baseline Who Discontinued Corticosteroid Use and Achieve CDAI < 150 Over Time | CDAI is used to quantify the signs and symptoms of subjects with Crohn's disease. The score includes the frequency of stools, abdominal pain and general well-being as well as the presence of complications, use of antidiarrheals, presence of abdominal mass, hematocrit and weight. CDAI generally ranges from 0 to 600 where higher scores indicate more severe disease. A score below 150 indicates remission. | Week 20, Week 28, Week 36, Week 44, Week 52 | 
| Percentage of Participants Taking Corticosteroids at Induction Baseline Who Discontinued Corticosteroid Use and Achieve Remission At Week 52 | Steroid-free remission at Week 52 was defined as both endoscopic remission at Week 52 and clinical remission at Week 52. Endoscopic remission: SES-CD ≤ 4 and at least 2 point reduction versus Induction Baseline and no subscore > 1 in any individual variable. Clinical remission: Average daily stool frequency ≤ 1.5 and not worse than baseline AND average daily abdominal pain ≤ 1.0 and not worse than Induction Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). See SES-CD description details in the first primary endpoint description of this record. | Baseline, Week 52 | 
| Percentage of Participants Taking Corticosteroids at Induction Baseline Who Discontinued Corticosteroid Use and Achieve Clinical Remission Over Time | Steroid-free clinical remission was defined as average daily stool frequency <= 1.5 and not worse than Induction Baseline AND average daily abdominal pain <= 1.0 and not worse than Induction Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). | Week 20, Week 28, Week 36, Week 44, Week 52 | 
| Percentage of Participants Taking Corticosteroids at Induction Baseline and With Daily Stool Frequency ≥ 4.0 or Daily Abdominal Pain ≥ 2.0 at Induction Baseline Who Discontinued Corticosteroid Use and Achieve Modified Clinical Remission Over Time | Steroid-free modified clinical remission was defined as average daily stool frequency <= 2.8 and not worse than Induction Baseline AND average daily abdominal pain <= 1.0 and not worse than Induction Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). | Week 20, Week 28, Week 36, Week 44, Week 52 | 
| Percentage of Participants Taking Corticosteroids at Induction Baseline Who Discontinued Corticosteroid Use and Achieve Endoscopic Remission at Week 52 | Steroid-free endoscopic remission was defined as SES-CD <= 4 and at least 2 points reduction versus Induction Baseline and no subscore > 1 in any individual variable. Details of the SES-CD scale are provided in the description of the first primary endpoint. | Baseline, Week 52 | 
| Percentage Of Participants Who Achieve CDAI < 150 Over Time During Extension Phase | CDAI is used to quantify the signs and symptoms of subjects with Crohn's disease. The score includes the frequency of stools, abdominal pain and general well-being as well as the presence of complications, use of antidiarrheals, presence of abdominal mass, hematocrit and weight. CDAI generally ranges from 0 to 600 where higher scores indicate more severe disease. A score below 150 indicates remission. | Week 20, Week 28, Week 36, Week 44, Week 52 | 
| Percentage of Participants With Decrease in CDAI ≥ 70 Points From Induction Baseline Over Time During Extension Phase | CDAI is used to quantify the signs and symptoms of subjects with Crohn's disease. The score includes the frequency of stools, abdominal pain and general well-being as well as the presence of complications, use of antidiarrheals, presence of abdominal mass, hematocrit and weight. CDAI generally ranges from 0 to 600 where higher scores indicate more severe disease. A 70-point decrease in the CDAI index refers to improvement in the disease activity from Baseline. | Week 20, Week 28, Week 36, Week 44, Week 52 | 
| Change From Induction Baseline in Fecal Calprotectin Level Over Time During Extension Phase |  | Baseline, Week 28, Week 52 | 
| Change From Induction Baseline in Hs-CRP Over Time During Extension Phase |  | Baseline, Week 20, Week 28, Week 36, Week 44, Week 52 | 
| Change From Induction Baseline in IBDQ at Week 52 | The IBDQ is a disease-specific instrument composed of 32 Likert-scaled items. The total score ranges from 32 to 224 using the 7-point response options, with higher scores indicating better health-related quality of life. The IBDQ scale contains 4 component subscales: bowel symptoms, systemic symptoms, emotional function, and social function. Each subscale can be computed with total scores ranging from 10 to 70, 5 to 35, 12 to 84, and 5 to 35, respectively. | Baseline, Week 52 | 
| Change From Induction Baseline in European Quality of Life (EuroQol) 5 Dimensions Questionnaire (EQ-5D) Index Score at Week 52 | The EQ-5D is a standardized instrument for use as a measure of health-related quality of life. The EQ-5D Index Score has five dimensions of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Health states are converted into a weighted health state index. These weights lie on a scale on which full health has a value of 1 and dead has a value of 0. A positive change represents an improvement in health-related quality of life. | Baseline, Week 52 | 
| Change From Induction Baseline in EQ-5D VAS at Week 52 | The EQ-5D is a standardized instrument for use as a measure of health-related quality of life. The EQ-5D VAS is a 20-cm scale with endpoints labeled best imaginable health and worst imaginable health anchored at 100 and 0, respectively. A positive change represents an improvement in health-related quality of life. | Baseline, Week 52 | 
| Cross Tabulation of Induction Baseline and Week 52 in Total Number of Extra-Intestinal Manifestations (EIMs) of Crohn's Disease | Presented as percentage of participants with given number of EIMs at Baseline (BL) and Week (Wk) 52. EIMs of Crohn's disease included anemia, autoimmune hepatitis, axial arthropathy, bronchiectasis, chronic obstructive pulmonary disease, episcleritis, erythema nodosum, iritis, nephrolithiasis, oral aphthous ulcers, peripheral arthropathy, primary sclerosing cholangitis, pyoderma gangrenosum, Sweet's syndrome, uveitis, and venous thromboembolism. | Baseline, Week 52 | 
| Percentage of Participants Who Achieve Remission at Week 52 Among Participants With Isolated Ileal Crohn's Disease at Baseline | Remission at Week 52 is defined as endoscopic remission at Week 52 AND clinical remission at Week 52. Endoscopic remission: SES-CD ≤ 4 and at least 2-point reduction versus Baseline and no subscore > 1 in any individual variable. Clinical remission: average daily stool frequency ≤ 1.5 and not worse than Baseline AND average daily abdominal pain ≤ 1.0 and not worse than Baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). Details of the SES-CD scale are provided in the description of the first primary endpoint. | Baseline, Week 52 | 
| Percentage of Participants Who Achieve Modified Clinical Remission at Week 52 Among Participants With Isolated Ileal Crohn's Disease at Baseline And Daily Stool Frequency ≥ 4.0 or Daily Abdominal Pain ≥ 2.0 at Induction Baseline | Modified clinical remission was defined as average daily stool frequency <= 2.8 and not worse than induction baseline AND average daily abdominal pain <= 1.0 and not worse than induction baseline. The very soft/liquid stool frequency and abdominal pain scores at a visit were the average of the daily values reported during the 7 usable days preceding the scheduled assessment visit. Abdominal Pain was rated on a 4-point scale from 0 (none) to 3 (severe). | Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Crohn's Disease