This is a Phase 2/3 study that comprises 5 substudies designed to evaluate the efficacy, safety, and tolerability of oral etrasimod as therapy in adult participants with moderately to severely active Crohn's disease (CD) who are refractory or intolerant to at least 1 of the current therapies for CD (ie, corticosteroids, immunosuppressants, or biologics). The overall duration of this study is up to 282 weeks, inclusive of the Screening Period, Treatment Period of up to 274 weeks (Induction, Extension or Maintenance, and Long-term Extension Periods), and the 4-Week Follow-Up Period for safety assessment.
This study includes 5 substudies: Substudy A - Phase 2: A Phase 2, randomized, double-blind, substudy to assess the safety, tolerability, and efficacy of oral etrasimod therapy in participants with moderate to severe CD that supports the selection of an induction and maintenance dose(s) for Phase 3. Substudy 1 - Phase 2: A Phase 2b randomized, double-blind, placebo-controlled, dose-ranging induction substudy to evaluate etrasimod as induction therapy and select an induction and maintenance dose(s) for continued evaluation in Phase 3. Substudy 2 - Induction: A Phase 3 randomized, double-blind, placebo-controlled substudy to evaluate etrasimod as induction therapy. Substudy 3 - Maintenance: A Phase 3 randomized, double-blind, placebo-controlled substudy to evaluate etrasimod as maintenance therapy. Participants from Substudy 1 and Substudy 2 will be enrolled in Substudy 3. Substudy 4 - Long-Term Extension: A long-term extension substudy for participants who complete at least 52 weeks of treatment. Participants from Substudy 3 and Substudy A are planned to be enrolled in Substudy 4.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
379
Center for Digestive Health (Endoscopy Location)
Dothan, Alabama, United States
Digestive Health Specialists
Dothan, Alabama, United States
Dothan Eyecare-Dr. Brent McKinley (OCT Location)
Dothan, Alabama, United States
Pulmonary Associates (PFT Location)
Dothan, Alabama, United States
Flowers Hospital (Imaging Location)
Dothan, Alabama, United States
Percentage of Participants With Endoscopic Response by Simple Endoscopic Score in Crohn's Disease (SES-CD) at Week 14: SSA
Endoscopic response: SES-CD score \<=4 and at least 2-point reduction from baseline with no subscore \>1 or \>=50% decrease from study baseline in SES-CD. SES-CD consisted of a composite score based on 4 components: size of ulcers, ulcerated surface, affected surface and presence of narrowing assessed in 5 bowel segments: ileum; right; transverse; left colon and rectum. Size of ulcers score: 0= none, 1= aphthous ulcers, 2= large ulcers and 3= very large ulcers. Ulcerated surface score: 0= none, 1= \<10%, 2= 10% - 30% and 3= \>30%. Affected surface score: 0= unaffected segment, 1= \<50%, 2= 50% - 75%, and 3= \>75%. Presence of narrowing score: 0= none, 1= single, can be passed, 2= multiple, can be passed, 3= cannot be passed. Total SES-CD= sum of each component score for all 5 bowel segments and ranged from 0 (no disease) to 60 (severe disease), higher score indicated more severe disease.
Time frame: Week 14 of SSA
Percentage of Participants With Endoscopic Response by SES-CD at Week 14: SS1
Endoscopic response: SES-CD score \<=4 and at least 2-point reduction from baseline with no subscore \>1 or \>=50% decrease from study baseline in SES-CD. SES-CD consisted of composite score based on 4 components: size of ulcers, ulcerated surface, affected surface and presence of narrowing assessed in 5 bowel segments: ileum; right; transverse; left colon and rectum. Size of ulcers score: 0= none, 1= aphthous ulcers, 2= large ulcers and 3= very large ulcers. Ulcerated surface score: 0= none, 1= \<10%, 2= 10% - 30% and 3= \>30%. Affected surface score: 0= unaffected segment, 1= \<50%, 2= 50% - 75%, and 3= \>75%. Presence of narrowing score: 0= none, 1= single, can be passed, 2= multiple can be passed, 3= cannot be passed. Total SES CD= sum of each component score for all 5 bowel segments and ranged from 0 (no disease)-60 (severe disease), higher score indicated more severe disease. Multiple imputation (MI) method used; percentage calculated based on average response rate from MI datasets.
Time frame: Week 14 of SS1
Percentage of Participants With Clinical Remission by CDAI at Week 52: SS3 Responder Cohort
Clinical remission was considered as CDAI score \<150. CDAI was a composite index consisting of a weighted scoring of 8 disease activity variables: number of liquid or soft stools; extent of abdominal pain graded from 0 (none) to 3 (severe); general well-being rating assessed from 0 (generally well) to 4 (terrible); presence of complications; taking diphenoxylate/atropine, loperamide or opiates for diarrhea; presence of an abdominal mass (0 as none, 2 as questionable, 5 as definite); hematocrit (HCT): 47 in men and 42 in women and percentage deviation from standard weight, lower bound -10. Total CDAI score was calculated as the sum of variable scores\*weighting factor and ranged from 0 (no disease) to 600 (severe disease), where higher scores indicated more severe disease.
Time frame: Week 52 of study
Percentage of Participants With Clinical Remission by CDAI at Week 52: SS3 Non-Responder Cohort
Clinical remission was considered as CDAI score \<150. CDAI was a composite index consisting of a weighted scoring of 8 disease activity variables: number of liquid or soft stools; extent of abdominal pain graded from 0 (none) to 3 (severe); general well-being rating assessed from 0 (generally well) to 4 (terrible); presence of complications; taking diphenoxylate/atropine, loperamide or opiates for diarrhea; presence of an abdominal mass (0 as none, 2 as questionable, 5 as definite); HCT: 47 in men and 42 in women and percentage deviation from standard weight, lower bound -10. Total CDAI score was calculated as the sum of variable scores\*weighting factor and ranged from 0 (no disease) to 600 (severe disease), where higher scores indicated more severe disease.
Time frame: Week 52 of study
Percentage of Participants With Endoscopic Response by SES-CD at Week 52: SS3 Responder Cohort
Endoscopic response: SES-CD score \<=4 and at least 2-point reduction from baseline with no subscore \>1 or \>=50% decrease from parent study (SS1) baseline in SES-CD. SES-CD consisted of composite score based on size of ulcers, ulcerated surface, affected surface and presence of narrowing assessed in 5 segments: ileum; right; transverse; left colon; rectum. Size of ulcers score: 0=none, 1=aphthous ulcers,2=large ulcers,3=very large ulcers. Ulcerated surface score: 0= none, 1= \<10%, 2= 10% - 30%, 3= \>30%. Affected surface score: 0= unaffected segment, 1= \<50%,2= 50%-75%,3= \>75%. Presence of narrowing score: 0=none,1=single, can be passed, 2=multiple, can be passed,3=cannot be passed. Total SES CD=sum of each domain score for all 5 bowel segments and ranged from 0 (no disease) to 60 (severe disease), higher score= more severe disease.
Time frame: Week 52 of study
Percentage of Participants With Endoscopic Response by SES-CD at Week 52: SS3 Non-Responder Cohort
Endoscopic response: SES-CD score \<=4 and at least 2-point reduction from baseline with no subscore \>1 or \>=50% decrease from parent study (SS1) baseline in SES-CD. SES-CD consisted of composite score based on size of ulcers, ulcerated surface, affected surface and presence of narrowing assessed in 5 segments: ileum; right, transverse; left colon; rectum. Size of ulcers score: 0=none, 1=aphthous ulcers,2=large ulcers,3=very large ulcers. Ulcerated surface score: 0= none, 1= \<10%, 2= 10% - 30%, 3= \>30%. Affected surface score: 0= unaffected segment, 1= \<50%,2= 50%-75%,3= \>75%. Presence of narrowing score: 0=none,1=single, can be passed, 2=multiple, can be passed,3=cannot be passed. Total SES CD=sum of each domain score for all 5 bowel segments and ranged from 0 (no disease) to 60 (severe disease), higher score= more severe disease.
Time frame: Week 52 of study
Percentage of Participants With Clinical Remission by CDAI at Week 14: SSA
Clinical remission was considered as CDAI score \<150. CDAI was a composite index consisting of a weighted scoring of 8 disease activity variables: number of liquid or soft stools; extent of abdominal pain graded from 0 (none) to 3 (severe); general well-being rating assessed from 0 (generally well) to 4 (terrible); presence of complications; taking diphenoxylate/atropine, loperamide or opiates for diarrhea; presence of an abdominal mass (0 as none, 2 as questionable, 5 as definite); HCT: 47 in men and 42 in women and percentage deviation from standard weight, lower bound -10. Total CDAI score was calculated as the sum of variable scores\*weighting factor and ranged from 0 (no disease) to 600 (severe disease), where higher scores indicated more severe disease.
Time frame: Week 14 of SSA
Change From Baseline in SES-CD Score at Week 14: SSA
SES-CD consisted of a composite score based on 4 components: size of ulcers, ulcerated surface, affected surface and presence of narrowing assessed in 5 bowel segments: ileum; right; transverse; left colon and rectum. Size of ulcers score: 0= none, 1= aphthous ulcers, 2= large ulcers and 3= very large ulcers. Ulcerated surface score: 0= none, 1= \<10%, 2= 10% - 30% and 3= \>30%. Affected surface score: 0= unaffected segment, 1= \<50%, 2= 50% - 75%, and 3= \>75%. Presence of narrowing score: 0= none, 1= single, can be passed, 2= multiple, can be passed, 3= cannot be passed. Total SES-CD= sum of each component score for all 5 bowel segments and ranged from 0 (no disease) to 60 (severe disease), higher score indicated more severe disease.
Time frame: Baseline (last measurement taken prior to the first dose of study treatment) and Week 14 of SSA
Change From Baseline in CDAI Score at Week 14: SSA
CDAI was a composite index consisting of a weighted scoring of 8 disease activity variables: number of liquid or soft stools; extent of abdominal pain graded from 0 (none) to 3 (severe); general well-being rating assessed from 0 (generally well) to 4 (terrible); presence of complications; taking diphenoxylate/atropine, loperamide or opiates for diarrhea; presence of an abdominal mass (0 as none, 2 as questionable, 5 as definite); HCT: 47 in men and 42 in women and percentage deviation from standard weight, lower bound -10. Total CDAI score was calculated as the sum of variable scores\*weighting factor and ranged from 0 (no disease) to 600 (severe disease), where higher scores indicated more severe disease.
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Digestive Health Specialists (Satellite Clinic Location)
Mobile, Alabama, United States
Premier Medical Group East (Opthalmology & Optometry Facility)
Mobile, Alabama, United States
Pulmonary Associates (Chest X-Ray & PFT Facility)
Mobile, Alabama, United States
Surgicare of Mobile (Endoscopy & Biopsy Facility)
Mobile, Alabama, United States
Arizona Retina Institute/ Phoenix Retina Associates(OCT)
Peoria, Arizona, United States
...and 500 more locations
Time frame: Baseline (last measurement taken prior to the first dose of study treatment) and Week 14 of SSA
Plasma Concentration of Etrasimod at 4 Hours Post-dose: SSA
The plasma concentration of etrasimod at 4 hours post-dose has been reported in this outcome measure.
Time frame: 4 hours post-dose on Day 1
Steady State Trough Concentration (Ctrough,ss) of Etrasimod From Week 2 to Week 14: SSA
The average steady-state Ctrough for Week 2 through 14 was calculated based on individual Ctrough data from Week 2, Week 6 and Week 14.
Time frame: From Week 2 to Week 14
Change From Baseline in Absolute Lymphocyte Count (ALC) at Week 14 in Induction Period: SSA
Time frame: Baseline (last measurement taken prior to the first dose of study treatment) and Week 14 of SSA
Percent Change From Baseline in ALC at Week 14 in Induction Period: SSA
Time frame: Baseline (last measurement taken prior to the first dose of study treatment) and Week 14 of SSA
Change From Baseline in ALC at Week 66 in Extension Period: SSA
Time frame: Baseline (last measurement taken prior to the first dose of study treatment) and Week 66 of SSA
Percent Change From Baseline in ALC at Week 66 in Extension Period: SSA
Time frame: Baseline (last measurement taken prior to the first dose of study treatment) and Week 66 of SSA
Change From Baseline in Fecal Calprotectin (FCP) Concentration at Week 14 in Induction Period: SSA
Time frame: Baseline (last measurement taken prior to the first dose of study treatment) and Week 14 of SSA
Percent Change From Baseline in FCP Concentration at Week 14 in Induction Period: SSA
Time frame: Baseline (last measurement taken prior to the first dose of study treatment) and Week 14 of SSA
Change From Baseline in FCP Concentration at Week 66 in Extension Period: SSA
Time frame: Baseline (last measurement taken prior to the first dose of study treatment) and Week 66 of SSA
Percent Change From Baseline in FCP Concentration at Week 66 in Extension Period: SSA
Time frame: Baseline (last measurement taken prior to the first dose of study treatment) and Week 66 of SSA
Change From Baseline in C-Reactive Protein (CRP) at Week 14 in Induction Period: SSA
Time frame: Baseline (last measurement taken prior to the first dose of study treatment) and Week 14 of SSA
Percent Change From Baseline in CRP at Week 14 in Induction Period: SSA
Time frame: Baseline (last measurement taken prior to the first dose of study treatment) and Week 14 of SSA
Change From Baseline in CRP at Week 66 in Extension Period: SSA
Time frame: Baseline (last measurement taken prior to the first dose of study treatment) and Week 66 of SSA
Percent Change From Baseline in CRP at Week 66 in Extension Period: SSA
Time frame: Baseline (last measurement taken prior to the first dose of study treatment) and Week 66 of SSA
Percentage of Participants With Clinical Remission by CDAI at Week 14: SS1
Clinical remission was considered as CDAI score \<150. CDAI was a composite index consisting of a weighted scoring of 8 disease activity variables: number of liquid or soft stools; extent of abdominal pain graded from 0 (none) to 3 (severe); general well-being rating assessed from 0 (generally well) to 4 (terrible); presence of complications; taking diphenoxylate/atropine, loperamide or opiates for diarrhea; presence of an abdominal mass (0 as none, 2 as questionable, 5 as definite); HCT: 47 in men and 42 in women and percentage deviation from standard weight, lower bound -10. Total CDAI score was calculated as the sum of variable scores\*weighting factor and ranged from 0 (no disease) to 600 (severe disease), where higher scores indicated more severe disease. MI method was used; percentage was calculated based on average response rate from MI datasets.
Time frame: Week 14 of SS1
Percentage of Participants With Clinical Remission by Patient Reported Outcomes 2 (PRO2) at Week 14: SS1
Clinical remission was defined as PRO2 score \<8. The PRO2 was a patient-reported outcome measure based on abdominal pain and stool frequency components of the CDAI. The abdominal pain rating was graded from 0 (none) to 3 (severe) each day for 7 days. The stool frequency was defined as number of liquid or soft stools each day for 7 days. Total PRO2 score was calculated as the sum of averaged abdominal pain/stool frequency variable scores\*weighting factor. The PRO2 score had a minimum score of 0 and had no upper bound, with a higher score indicating more frequent stools and more severe abdominal pain. MI method was used; percentage was calculated based on average response rate from MI datasets.
Time frame: Week 14 of SS1
Percentage of Participants With Clinical Remission by CDAI at Week 52 Among Participants With Clinical Remission by CDAI at SS3 Baseline: SS3 Responder Cohort
Clinical remission was CDAI score \<150. CDAI was a composite index consisting of weighted scoring of 8 disease activity variables: number of liquid or soft stools; extent of abdominal pain graded from 0 (none) to 3 (severe); general well-being rating assessed from 0 (generally well) to 4 (terrible); presence of complications; taking diphenoxylate/atropine, loperamide or opiates for diarrhea; presence of abdominal mass (0 as none, 2 as questionable, 5 as definite); HCT: 47 in men and 42 in women and percentage deviation from standard weight, lower bound -10. Total CDAI score: sum of variable scores\*weighting factor and ranged from 0 (no disease) to 600 (severe disease), where higher scores= more severe disease. SS3 Baseline was last non-missing measurement taken prior to date of FMD of SS3.
Time frame: Week 52 of study
Percentage of Participants With Clinical Remission by CDAI at Week 52 Among Participants With Clinical Remission by CDAI at SS3 Baseline: SS3 Non-Responder Cohort
Clinical remission was CDAI score \<150. CDAI was a composite index consisting of weighted scoring of 8 disease activity variables: number of liquid or soft stools; extent of abdominal pain graded from 0 (none) to 3 (severe); general well-being rating assessed from 0 (generally well) to 4 (terrible); presence of complications; taking diphenoxylate/atropine, loperamide or opiates for diarrhea; presence of abdominal mass (0 as none, 2 as questionable, 5 as definite); HCT: 47 in men and 42 in women and percentage deviation from standard weight, lower bound -10. Total CDAI score: sum of variable scores\*weighting factor and ranged from 0 (no disease) to 600 (severe disease), where higher scores= more severe disease. SS3 Baseline was last non-missing measurement taken prior to date of FMD of SS3.
Time frame: Week 52 of study
Percentage of Participants With Endoscopic Response at Week 52 Among Participants With Endoscopic Response at SS3 Baseline: SS3 Responder Cohort
Endoscopic response: SES-CD score \<=4 and at least 2-point reduction from baseline with no subscore \>1 or \>=50% decrease from parent study (SS1) baseline in SES-CD. SES-CD= composite score based on 4 components: size of ulcers, ulcerated surface, affected surface, presence of narrowing in 5 segments: ileum; right; transverse; left colon; rectum. Size of ulcers score: 0=none,1= aphthous ulcers, 2= large ulcers, 3= very large ulcers. Ulcerated surface score: 0= none,1= \<10%, 2= 10%-30%, 3= \>30%. Affected surface score: 0= unaffected segment, 1= \<50%, 2= 50%-75%,3= \>75%. Presence of narrowing score: 0= none,1= single, can be passed, 2= multiple can be passed, 3= can't be passed. Total SES CD=sum of component scores for 5 bowel segments and ranged from 0 (no disease) - 60 (severe disease), higher score indicated more severe disease. SS3 Baseline was last non-missing measurement taken prior to FMD date.
Time frame: Week 52 of study
Percentage of Participants With Endoscopic Response at Week 52 Among Participants With Endoscopic Response at SS3 Baseline: SS3 Non-Responder Cohort
Endoscopic response: SES-CD score \<=4 and at least 2-point reduction from baseline with no subscore \>1 or \>=50% decrease from parent study (SS1) baseline in SES-CD. SES-CD= composite score based on 4 components: size of ulcers, ulcerated surface, affected surface, presence of narrowing in 5 segments: ileum; right; transverse; left colon; rectum. Size of ulcers score: 0=none,1= aphthous ulcers, 2= large ulcers, 3= very large ulcers. Ulcerated surface score: 0= none,1= \<10%, 2= 10%-30%, 3= \>30%. Affected surface score: 0= unaffected segment, 1= \<50%, 2= 50%-75%,3= \>75%. Presence of narrowing score: 0= none,1= single, can be passed, 2= multiple can be passed, 3= can't be passed. Total SES CD=sum of component scores for 5 bowel segments and ranged from 0 (no disease) - 60 (severe disease), higher score indicated more severe disease. SS3 Baseline was last non-missing measurement taken prior to FMD date.
Time frame: Week 52 of study
Percentage of Participants With Corticosteroid-Free Clinical Remission by CDAI at Week 52 Among Participants Receiving Corticosteroids at SS3 Baseline: SS3 Responder Cohort
Corticosteroid-free remission: CDAI score \<150 without receiving corticosteroids for \>=8 weeks prior to Week 52 (for participants receiving corticosteroids at baseline). CDAI: composite index consisting of weighted scoring of 8 disease activity variables: number of liquid stools; extent of abdominal pain from 0 (none)-3 (severe); general well-being from 0 (generally well)-4 (terrible); presence of complications; taking diphenoxylate/atropine, loperamide or opiates for diarrhea; presence of abdominal mass (0=none, 2=questionable, 5=definite); HCT 47 in men and 42 in women; percentage deviation from standard weight, lower bound -10. Total CDAI score=sum of variable scores\*weighting factor and was from 0 (no disease)-600 (severe disease), higher score indicated more severe disease. SS3 Baseline was last non-missing measurement taken prior to date of FMD of SS3.
Time frame: Week 52 of study
Percentage of Participants With Corticosteroid-Free Clinical Remission by CDAI at Week 52 Among Participants Receiving Corticosteroids at SS3 Baseline: SS3 Non-Responder Cohort
Corticosteroid-free remission: CDAI score \<150 without receiving corticosteroids for \>=8 weeks prior to Week 52 (for participants receiving corticosteroids at baseline). CDAI: composite index consisting of weighted scoring of 8 disease activity variables: number of liquid stools; extent of abdominal pain from 0 (none)-3 (severe); general well-being from 0 (generally well)-4 (terrible); presence of complications; taking diphenoxylate/atropine, loperamide or opiates for diarrhea; presence of abdominal mass (0=none, 2=questionable, 5=definite); HCT 47 in men and 42 in women; percentage deviation from standard weight, lower bound -10. Total CDAI score=sum of variable scores\*weighting factor and was from 0 (no disease)-600 (severe disease), higher score indicated more severe disease. SS3 Baseline was last non-missing measurement taken prior to date of FMD of SS3.
Time frame: Week 52 of study
Percentage of Participants With Endoscopic Remission at Week 52: SS3 Responder Cohort
Endoscopic remission: SES-CD score \<=4 and at least 2-point reduction from baseline with no sub-score \>1. SES-CD consisted of a composite score based on 4 components: size of ulcers, ulcerated surface, affected surface and presence of narrowing assessed in 5 segments: ileum; right; transverse; left colon and rectum. Size of ulcers score: 0=none, 1=aphthous ulcers, 2=large ulcers and 3=very large ulcers. Ulcerated surface score: 0= none, 1= \<10%, 2= 10% - 30% and 3= \>30%. Affected surface score: 0= unaffected segment, 1= \<50%, 2= 50% - 75%, and 3= \>75%. Presence of narrowing score: 0=none, 1= single, can be passed, 2=multiple, can be passed, 3= cannot be passed. Total SES CD=sum of each component score for all 5 bowel segments and ranged from 0 (no disease)-60 (severe disease), higher score indicated more severe disease.
Time frame: Week 52 of study
Percentage of Participants With Endoscopic Remission at Week 52: SS3 Non-Responder Cohort
Endoscopic remission: SES-CD score \<=4 and at least 2-point reduction from baseline with no sub-score \>1. SES-CD consisted of a composite score based on 4 components: size of ulcers, ulcerated surface, affected surface and presence of narrowing assessed in 5 segments: ileum; right; transverse; left colon and rectum. Size of ulcers score: 0=none, 1=aphthous ulcers, 2=large ulcers and 3=very large ulcers. Ulcerated surface score: 0= none, 1= \<10%, 2= 10% - 30% and 3= \>30%. Affected surface score: 0= unaffected segment, 1= \<50%, 2= 50% - 75%, and 3= \>75%. Presence of narrowing score: 0=none, 1= single, can be passed, 2=multiple, can be passed, 3= cannot be passed. Total SES CD=sum of each component score for all 5 bowel segments and ranged from 0 (no disease)-60 (severe disease), higher score indicated more severe disease.
Time frame: Week 52 of study
Percentage of Participants With Clinical Remission by PRO2 at Week 52: SS3 Responder Cohort
Clinical remission was defined as PRO2 score \<8. The PRO2 was a patient-reported outcome measure based on abdominal pain and stool frequency components of the CDAI. The abdominal pain rating was graded from 0 (none) to 3 (severe) each day for 7 days. The stool frequency was defined as number of liquid or soft stools each day for 7 days. Total PRO2 score was calculated as the sum of averaged abdominal pain/stool frequency variable scores\*weighting factor. The PRO2 score had a minimum score of 0 and had no upper bound, with a higher score indicating more frequent stools and more severe abdominal pain.
Time frame: Week 52 of study
Percentage of Participants With Clinical Remission by PRO2 at Week 52: SS3 Non-Responder Cohort
Clinical remission was defined as PRO2 score \<8. The PRO2 was a patient-reported outcome measure based on abdominal pain and stool frequency components of the CDAI. The abdominal pain rating was graded from 0 (none) to 3 (severe) each day for 7 days. The stool frequency was defined as number of liquid or soft stools each day for 7 days. Total PRO2 score was calculated as the sum of averaged abdominal pain/stool frequency variable scores\*weighting factor. The PRO2 score had a minimum score of 0 and had no upper bound, with a higher score indicating more frequent stools and more severe abdominal pain.
Time frame: Week 52 of study
Percentage of Participants With Clinical Response or Endoscopic Response at Week 52: SS3 Responder Cohort
Clinical response: clinical remission CDAI or \>=100-point decrease from baseline in CDAI score where, clinical remission CDAI=CDAI \<150. CDAI: composite index consisting of weighted scoring of 8 disease activity variables. Total CDAI: sum of variable scores\*weighting factor and ranged from 0 (no disease) - 600 (severe disease), higher scores indicated more severe disease. Endoscopic response: SES-CD score \<=4 and at least 2-point reduction from baseline with no subscore \>1 or \>=50% decrease from baseline in SES-CD. SES-CD comprised of 4 components assessed for 5 bowel segments. Each component score ranged from 0-3, higher scores indicated more severe condition. Total SES CD: sum of each component score of 5 bowel segments and ranged from 0 (no D) - 60 (severe disease), higher score indicated more severe disease. Percentage of participants with clinical response or endoscopic response at Week 52 is reported.
Time frame: Week 52 of study
Percentage of Participants With Clinical Response or Endoscopic Response at Week 52: SS3 Non-Responder Cohort
Clinical response: clinical remission CDAI or \>=100-point decrease from baseline in CDAI score where, clinical remission CDAI=CDAI \<150. CDAI: composite index consisting of weighted scoring of 8 disease activity variables. Total CDAI: sum of variable scores\*weighting factor and ranged from 0 (no disease) - 600 (severe disease), higher scores indicated more severe disease. Endoscopic response: SES-CD score \<=4 and at least 2-point reduction from baseline with no subscore \>1 or \>=50% decrease from baseline in SES-CD. SES-CD comprised of 4 components assessed for 5 bowel segments. Each component score ranged from 0-3, higher scores indicated more severe condition. Total SES CD: sum of each component score of 5 bowel segments and ranged from 0 (no D) - 60 (severe disease), higher score indicated more severe disease. Percentage of participants with clinical response or endoscopic response at Week 52 is reported.
Time frame: Week 52 of study
Change From Baseline in CDAI Score at Weeks 20, 28, 36, 44 and 52: SS3 Responder Cohort
CDAI was a composite index consisting of a weighted scoring of 8 disease activity variables: number of liquid or soft stools; extent of abdominal pain graded from 0 (none) to 3 (severe); general well-being rating assessed from 0 (generally well) to 4 (terrible); presence of complications; taking diphenoxylate/atropine, loperamide or opiates for diarrhea; presence of an abdominal mass (0 as none, 2 as questionable, 5 as definite); HCT 47 in men and 42 in women and percentage deviation from standard weight, lower bound -10. Total CDAI score was calculated as the sum of variable scores\*weighting factor and ranged from 0 (no disease) to 600 (severe disease), where higher scores indicated more severe disease. SS3 Baseline was last non-missing measurement taken prior to date of FMD of SS3.
Time frame: Baseline, study Weeks 20, 28, 36, 44, 52
Change From Baseline in CDAI Score at Weeks 20, 28, 36, 44 and 52: SS3 Non-Responder Cohort
CDAI was a composite index consisting of a weighted scoring of 8 disease activity variables: number of liquid or soft stools; extent of abdominal pain graded from 0 (none) to 3 (severe); general well-being rating assessed from 0 (generally well) to 4 (terrible); presence of complications; taking diphenoxylate/atropine, loperamide or opiates for diarrhea; presence of an abdominal mass (0 as none, 2 as questionable, 5 as definite); HCT 47 in men and 42 in women and percentage deviation from standard weight, lower bound -10. Total CDAI score was calculated as the sum of variable scores\*weighting factor and ranged from 0 (no disease) to 600 (severe disease), where higher scores indicated more severe disease. SS3 Baseline was last non-missing measurement taken prior to date of FMD of SS3.
Time frame: Baseline, study Weeks 20, 28, 36, 44, 52
Percentage of Participants With Clinical Response by CDAI at Week 52 Among Participants With Clinical Response by CDAI at SS3 Baseline: SS3 Responder Cohort
Clinical Response was clinical remission by CDAI or \>=100-point decrease from baseline in CDAI score where, clinical remission CDAI= CDAI \<150. CDAI: composite index consisting of weighted scoring of 8 disease activity variables: number of liquid or soft stools; extent of abdominal pain graded from 0 (none)-3 (severe); general well-being rating assessed from 0 (generally well) - 4 (terrible); presence of complications; taking diphenoxylate/atropine, loperamide/opiates for diarrhea; presence of an abdominal mass (0=none, 2=questionable, 5=definite); HCT 47 in men and 42 in women and percentage deviation from standard weight, lower bound -10. Total CDAI score= sum of variable scores\*weighting factor and ranged from 0 (no disease) - 600 (severe disease), where higher scores indicated more severe disease. SS3 Baseline= last non-missing measurement taken prior to date of FMD of SS3.
Time frame: Week 52 of study
Percentage of Participants With Clinical Response by CDAI at Week 52 Among Participants With Clinical Response by CDAI at SS3 Baseline: SS3 Non-Responder Cohort
Clinical Response was clinical remission by CDAI or \>=100-point decrease from baseline in CDAI score where, clinical remission CDAI= CDAI \<150. CDAI: composite index consisting of weighted scoring of 8 disease activity variables: number of liquid or soft stools; extent of abdominal pain graded from 0 (none)-3 (severe); general well-being rating assessed from 0 (generally well) - 4 (terrible); presence of complications; taking diphenoxylate/atropine, loperamide/opiates for diarrhea; presence of an abdominal mass (0=none, 2=questionable, 5=definite); HCT 47 in men and 42 in women and percentage deviation from standard weight, lower bound -10. Total CDAI score= sum of variable scores\*weighting factor and ranged from 0 (no disease) - 600 (severe disease), where higher scores indicated more severe disease. SS3 Baseline= last non-missing measurement taken prior to date of FMD of SS3.
Time frame: Week 52 of study
Change From Baseline in Crohn's Disease Patient-Reported Outcomes (CD-PRO) Module Scores at Weeks 28 and 52: SS3 Responder Cohort
The CD-PRO was a validated instrument designed to assess the signs, symptoms, and impact of CD through 6 modules: Systemic Symptoms, Coping Strategies, Daily Life Impact, Emotional Impact, Bowel Signs and Symptoms and Functional Symptoms. Each module ranged from 0 to 16, where higher scores indicated more severe disease. SS3 Baseline was defined as last non-missing measurement taken prior to date of FMD of SS3.
Time frame: Baseline, study Weeks 28 and 52
Change From Baseline in Crohn's Disease Patient-Reported Outcomes (CD-PRO) Module Scores at Weeks 28 and 52: SS3 Non-Responder Cohort
The CD-PRO was a validated instrument designed to assess the signs, symptoms, and impact of CD through 6 modules: Systemic Symptoms, Coping Strategies, Daily Life Impact, Emotional Impact, Bowel Signs and Symptoms and Functional Symptoms. Each module ranged from 0 to 16, where higher scores indicated more severe disease. SS3 Baseline was defined as last non-missing measurement taken prior to date of FMD of SS3.
Time frame: Baseline, study Weeks 28 and 52
Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) at Weeks 28 and 52: SS3 Responder Cohort
The IBDQ was a validated 32 item questionnaire used to assess health related quality of life in participants with IBD. Response to each of the questions ranged from 1 to 7 where higher scores indicated better quality of life. The total IBDQ scores were calculated as sum of individual item scores and ranged from 32 (very poor health-related quality of life) to 224 (perfect health-related quality of life) where higher scores indicated better quality of life. SS3 Baseline was defined as last non-missing measurement taken prior to date of FMD of SS3.
Time frame: Baseline, study Weeks 28 and 52
Change From Baseline in IBDQ at Weeks 28 and 52: SS3 Non-Responder Cohort
The IBDQ was a validated 32 item questionnaire used to assess health related quality of life in participants with IBD. Response to each of the questions ranged from 1 to 7 where higher scores indicated better quality of life. The total IBDQ scores were calculated as sum of individual item scores and ranged from 32 (very poor health-related quality of life) to 224 (perfect health-related quality of life) where higher scores indicated better quality of life. SS3 Baseline was defined as last non-missing measurement taken prior to date of FMD of SS3.
Time frame: Baseline, study Weeks 28 and 52
Change From Baseline in Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) at Weeks 28 and 52: SS3 Responder Cohort
The SF-36 was a health-related survey that assessed participant's health status and consisted of 36 questions measuring 8 health domains: physical functioning, bodily pain, role limitations due to physical problems, role limitations due to emotional problems, general health perceptions, mental health, social function and vitality. The 8 domains are combined to form 2 component scores mental (MCS) and physical (PCS). MCS consisted of social functioning, vitality, mental health, and role-emotional scales. PCS consisted of physical functioning, bodily pain, role-physical, and general health scales. Each domain was scored by summing the individual items and transforming the total SF-36 scores into a 0 to 100 scale with higher scores indicating better health status. SS3 Baseline= last non-missing measurement taken prior to date of FMD of SS3.
Time frame: Baseline, study Weeks 28 and 52
Change From Baseline in SF-36 at Weeks 28 and 52: SS3 Non-Responder Cohort
The SF-36 was a health-related survey that assessed participant's health status and consisted of 36 questions measuring 8 health domains: physical functioning, bodily pain, role limitations due to physical problems, role limitations due to emotional problems, general health perceptions, mental health, social function and vitality. The 8 domains are combined to form 2 component scores MCS and PCS. MCS consisted of social functioning, vitality, mental health, and role-emotional scales. PCS consisted of physical functioning, bodily pain, role-physical, and general health scales. Each domain was scored by summing the individual items and transforming the total SF-36 scores into a 0 to 100 scale with higher scores indicating better health status. SS3 Baseline= last non-missing measurement taken prior to date of FMD of SS3.
Time frame: Baseline, study Weeks 28 and 52
Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) at Weeks 28 and 52: SS3 Responder Cohort
The FACIT-F was a participant completed questionnaire consisting of 13 items that assess fatigue. Participants responded to each item on a 5-point scale based on their experience of fatigue during the past 7 days (0 = not at all; 1 = a little bit; 2 =somewhat; 3 = quite a bit; 4 = very much). Instrument scoring yielded a total FACIT-F score range from 0 to 52 (negatively worded items were reversed during analysis), with higher scores representing better participant status (less fatigue). SS3 Baseline= last non-missing measurement taken prior to date of FMD of SS3.
Time frame: Baseline, study Weeks 28 and 52
Change From Baseline in FACIT-F at Weeks 28 and 52: SS3 Non-Responder Cohort
The FACIT-F was a participant completed questionnaire consisting of 13 items that assess fatigue. Participants responded to each item on a 5-point scale based on their experience of fatigue during the past 7 days (0 = not at all; 1 = a little bit; 2 =somewhat; 3 = quite a bit; 4 = very much). Instrument scoring yielded a total FACIT-F score range from 0 to 52 (negatively worded items were reversed during analysis), with higher scores representing better participant status (less fatigue). SS3 Baseline= last non-missing measurement taken prior to date of FMD of SS3.
Time frame: Baseline, study Weeks 28 and 52
Percentage of Participants With Clinical Remission by PRO2 at Week 52 Among Participants With Clinical Remission by PRO2 at SS3 Baseline: SS3 Responder Cohort
Clinical remission was defined as PRO2 score \<8. The PRO2 was a patient-reported outcome measure based on abdominal pain and stool frequency components of the CDAI. The abdominal pain rating was graded from 0 (none) to 3 (severe) each day for 7 days. The stool frequency was defined as number of liquid or soft stools each day for 7 days. Total PRO2 score was calculated as the sum of averaged abdominal pain/stool frequency variable scores\*weighting factor. The PRO2 score had a minimum score of 0 and had no upper bound, with a higher score indicating more frequent stools and more severe abdominal pain. SS3 Baseline was defined as last non-missing measurement taken prior to date of FMD of SS3.
Time frame: Week 52 of study
Percentage of Participants With Clinical Remission by PRO2 at Week 52 Among Participants With Clinical Remission by PRO2 at Study Entry: SS3 Non-Responder Cohort
Clinical remission was defined as PRO2 score \<8. The PRO2 was a patient-reported outcome measure based on abdominal pain and stool frequency components of the CDAI. The abdominal pain rating was graded from 0 (none) to 3 (severe) each day for 7 days. The stool frequency was defined as number of liquid or soft stools each day for 7 days. Total PRO2 score was calculated as the sum of averaged abdominal pain/stool frequency variable scores\*weighting factor. The PRO2 score had a minimum score of 0 and had no upper bound, with a higher score indicating more frequent stools and more severe abdominal pain. SS3 Baseline was defined as last non-missing measurement taken prior to date of FMD of SS3.
Time frame: Week 52 of study
Change From Baseline in PRO2 Scores at Weeks 20, 28, 36, 44 and 52: SS3 Responder Cohort
The PRO2 was a patient-reported outcome measure based on abdominal pain and stool frequency components of the CDAI. The abdominal pain rating was graded from 0 (none) to 3 (severe) each day for 7 days. The stool frequency was defined as number of liquid or soft stools each day for 7 days. Total PRO2 score was calculated as the sum of averaged abdominal pain/stool frequency variable scores\*weighting factor. The PRO2 score had a minimum score of 0 and had no upper bound, with a higher score indicating more frequent stools and more severe abdominal pain. SS3 Baseline was defined as last non-missing measurement taken prior to date of FMD of SS3.
Time frame: Baseline, study Weeks 20, 28, 36, 44 and 52
Change From Baseline in PRO2 Scores at Weeks 20, 28, 36, 44 and 52: SS3 Non-Responder Cohort
The PRO2 was a patient-reported outcome measure based on abdominal pain and stool frequency components of the CDAI. The abdominal pain rating was graded from 0 (none) to 3 (severe) each day for 7 days. The stool frequency was defined as number of liquid or soft stools each day for 7 days. Total PRO2 score was calculated as the sum of averaged abdominal pain/stool frequency variable scores\*weighting factor. The PRO2 score had a minimum score of 0 and had no upper bound, with a higher score indicating more frequent stools and more severe abdominal pain. SS3 Baseline was defined as last non-missing measurement taken prior to date of FMD of SS3.
Time frame: Baseline, study Weeks 20, 28, 36, 44 and 52
Time to Remission by PRO2 and FCP Concentrations: SS3 Responder Cohort
Time to remission by PRO2 and FCP concentrations was defined as time to onset of clinical remission by PRO2 and FCP normalization. Clinical remission by PRO2 was defined as PRO2 score \<8. Normalization of FCP was defined as FCP \<=150 milligrams per kilogram. The PRO2 was a patient-reported outcome measure based on abdominal pain and stool frequency components of the CDAI. The abdominal pain rating was graded from 0 (none) to 3 (severe) each day for 7 days. The stool frequency was defined as number of liquid or soft stools each day for 7 days. Total PRO2 score was calculated as the sum of averaged abdominal pain/stool frequency variable scores\*weighting factor. The PRO2 score had a minimum score of 0 and had no upper bound, with a higher score indicating more frequent stools and more severe abdominal pain. Participants who did not achieve remission or discontinued from study were censored at 7 days after last dose of study drug.
Time frame: From first maintenance dose in SS3 until date of clinical remission and FCP normalization or censoring date (maximum up to 42 weeks)
Time to Remission by PRO2 and FCP Concentrations: SS3 Non-Responder Cohort
Time to remission by PRO2 and FCP concentrations was defined as time to onset of clinical remission by PRO2 and FCP normalization. Clinical remission by PRO2 was defined as PRO2 score \<8. Normalization of FCP was defined as FCP \<=150 milligrams per kilogram. The PRO2 was a patient-reported outcome measure based on abdominal pain and stool frequency components of the CDAI. The abdominal pain rating was graded from 0 (none) to 3 (severe) each day for 7 days. The stool frequency was defined as number of liquid or soft stools each day for 7 days. Total PRO2 score was calculated as the sum of averaged abdominal pain/stool frequency variable scores\*weighting factor. The PRO2 score had a minimum score of 0 and had no upper bound, with a higher score indicating more frequent stools and more severe abdominal pain. Participants who did not achieve remission or discontinued from study were censored at 7 days after last dose of study drug.
Time frame: From first maintenance dose in SS3 until date of clinical remission and FCP normalization or censoring date (maximum up to 42 weeks)
Time to Response by PRO2 and FCP Concentrations: SS3 Responder Cohort
Time to response by PRO2 and FCP concentrations: time to onset of PRO2 response and FCP normalization. Clinical response by PRO2: clinical remission by PRO2 or \>= 8-point decrease from baseline in PRO2 score. Clinical remission by PRO2: PRO2 score \<8. Normalization of FCP: FCP \<=150 milligrams per kilogram. The PRO2 was a patient-reported outcome measure based on abdominal pain and stool frequency components of the CDAI. The abdominal pain rating was graded from 0 (none) to 3 (severe) each day for 7 days. The stool frequency was defined as number of liquid or soft stools each day for 7 days. Total PRO2 score was calculated as the sum of averaged abdominal pain/stool frequency variable scores\*weighting factor. The PRO2 score had a minimum score of 0 and had no upper bound, with a higher score indicating more frequent stools and more severe abdominal pain. Participants who did not achieve response or discontinued from study were censored at 7 days after last dose of study drug.
Time frame: From first maintenance dose in SS3 until date of clinical response and FCP normalization or censoring date (maximum up to 42 weeks)
Time to Response by PRO2 and FCP Concentrations: SS3 Non-Responder Cohort
Time to response by PRO2 and FCP concentrations: time to onset of PRO2 response and FCP normalization. Clinical response by PRO2: clinical remission by PRO2 or \>= 8-point decrease from baseline in PRO2 score. Clinical remission by PRO2: PRO2 score \<8. Normalization of FCP: FCP \<=150 milligrams per kilogram. The PRO2 was a patient-reported outcome measure based on abdominal pain and stool frequency components of the CDAI. The abdominal pain rating was graded from 0 (none) to 3 (severe) each day for 7 days. The stool frequency was defined as number of liquid or soft stools each day for 7 days. Total PRO2 score was calculated as the sum of averaged abdominal pain/stool frequency variable scores\*weighting factor. The PRO2 score had a minimum score of 0 and had no upper bound, with a higher score indicating more frequent stools and more severe abdominal pain. Participants who did not achieve response or discontinued from study were censored at 7 days after last dose of study drug.
Time frame: From first maintenance dose in SS3 until date of clinical response and FCP normalization or censoring date (maximum up to 42 weeks)
Change From Baseline in SES-CD Score at Week 52: SS3 Responder Cohort
SES-CD was an endoscopic grading system which consisted of composite score based on 4 components: size of ulcers, ulcerated surface, affected surface and presence of narrowing assessed in 5 segments: ileum; right; transverse; left colon and rectum. Size of ulcers score: 0= none, 1= aphthous ulcers, 2=large ulcers and 3=very large ulcers. Ulcerated surface score: 0=none, 1= \<10%, 2= 10% - 30% and 3= \>30%. Affected surface score: 0=unaffected segment, 1= \<50%, 2= 50% - 75%, and 3= \>75%. Presence of narrowing score: 0=none, 1=single, can be passed, 2=multiple can be passed, 3=cannot be passed. Total SES CD= sum of each component score for all 5 bowel segments and ranged from 0 (no disease)-60 (severe disease), higher score indicated more severe disease. SS3 Baseline= last non-missing measurement taken prior to date of FMD of SS3.
Time frame: Baseline and Week 52 of study
Change From Baseline in SES-CD Score at Week 52: SS3 Non-Responder Cohort
SES-CD was an endoscopic grading system which consisted of composite score based on 4 components: size of ulcers, ulcerated surface, affected surface and presence of narrowing assessed in 5 segments: ileum; right; transverse; left colon and rectum. Size of ulcers score: 0= none, 1= aphthous ulcers, 2=large ulcers and 3=very large ulcers. Ulcerated surface score: 0=none, 1= \<10%, 2= 10% - 30% and 3= \>30%. Affected surface score: 0=unaffected segment, 1= \<50%, 2= 50% - 75%, and 3= \>75%. Presence of narrowing score: 0=none, 1=single, can be passed, 2=multiple can be passed, 3=cannot be passed. Total SES CD= sum of each component score for all 5 bowel segments and ranged from 0 (no disease)-60 (severe disease), higher score indicated more severe disease. SS3 Baseline= last non-missing measurement taken prior to date of FMD of SS3.
Time frame: Baseline and Week 52 of study
Percentage of Participants With Endoscopic Response and Clinical Remission by PRO2 at Week 52: SS3 Responder Cohort
Endoscopic response: SES-CD score \<=4 and at least 2-point reduction from baseline with no subscore \>1 or \>=50% decrease from parent study (SS1) baseline in SES-CD. SES-CD had 4 components assessed for 5 bowel segments where, each component score ranged from 0 to 3, higher scores=more severe condition. Total SES CD score was determined by sum of each component score for all 5 bowel segments and ranged from 0-60, higher score=more severe disease. Clinical remission by PRO2: PRO2 score \<8. PRO2 was patient-reported outcome measure based on abdominal pain and stool frequency components of CDAI. Abdominal pain graded from 0 (none)-3 (severe) each day for 7 days. Stool frequency was number of liquid or soft stools each day for 7 days. Total PRO2 score calculated as sum of averaged abdominal pain/stool frequency variable scores\*weighting factor. PRO2 score had minimum score of 0 and had no upper bound, with higher score indicating more frequent stools and more severe abdominal pain.
Time frame: Week 52 of study
Percentage of Participants With Endoscopic Response and Clinical Remission by PRO2 at Week 52: SS3 Non-Responder Cohort
Endoscopic response: SES-CD score \<=4 and at least 2-point reduction from baseline with no subscore \>1 or \>=50% decrease from parent study (SS1) baseline in SES-CD. SES-CD had 4 components assessed for 5 bowel segments where, each component score ranged from 0 to 3, higher scores=more severe condition. Total SES CD score was determined by sum of each component score for all 5 bowel segments and ranged from 0-60, higher score=more severe disease. Clinical remission by PRO2: PRO2 score \<8. PRO2 was patient-reported outcome measure based on abdominal pain and stool frequency components of CDAI. Abdominal pain graded from 0 (none)-3 (severe) each day for 7 days. Stool frequency was number of liquid or soft stools each day for 7 days. Total PRO2 score calculated as sum of averaged abdominal pain/stool frequency variable scores\*weighting factor. PRO2 score had minimum score of 0 and had no upper bound, with higher score indicating more frequent stools and more severe abdominal pain.
Time frame: Week 52 of study
Percentage of Participants With Endoscopic Remission and Clinical Remission by PRO2 at Week 52: SS3 Responder Cohort
Endoscopic remission: SES-CD \<=4 and at least 2-point reduction from baseline with no sub-score \>1. SES-CD comprised of 4 components assessed for 5 bowel segments where, each component score ranged from 0 to 3, higher scores indicated more severe condition. Total SES CD score was determined by sum of each component score for all 5 bowel segments and ranged from 0 to 60, higher score indicated more severe disease. Clinical remission by PRO2 was defined as PRO2 score \<8. PRO2 was patient-reported outcome measure based on abdominal pain and stool frequency components of CDAI. The abdominal pain rating was graded from 0 (none) to 3 (severe) each day for 7 days. Stool frequency was number of liquid or soft stools each day for 7 days. Total PRO2 score was calculated as sum of averaged abdominal pain/stool frequency variable scores\*weighting factor. PRO2 score had a minimum score of 0 and had no upper bound, with higher score indicating more frequent stools and more severe abdominal pain.
Time frame: Week 52 of study
Percentage of Participants With Endoscopic Remission and Clinical Remission by PRO2 at Week 52: SS3 Non-Responder Cohort
Endoscopic remission: SES-CD \<=4 and at least 2-point reduction from baseline with no sub-score \>1. SES-CD comprised of 4 components assessed for 5 bowel segments where, each component score ranged from 0 to 3, higher scores indicated more severe condition. Total SES CD score was determined by sum of each component score for all 5 bowel segments and ranged from 0 to 60, higher score indicated more severe disease. Clinical remission by PRO2 was defined as PRO2 score \<8. PRO2 was patient-reported outcome measure based on abdominal pain and stool frequency components of CDAI. The abdominal pain rating was graded from 0 (none) to 3 (severe) each day for 7 days. Stool frequency was number of liquid or soft stools each day for 7 days. Total PRO2 score was calculated as sum of averaged abdominal pain/stool frequency variable scores\*weighting factor. PRO2 score had a minimum score of 0 and had no upper bound, with higher score indicating more frequent stools and more severe abdominal pain.
Time frame: Week 52 of study
Number of Participants According to Markedly Abnormal Criteria for Electrocardiogram (ECG) Parameters: SS4
Pre-defined markedly abnormal criteria for ECG parameters included: QT interval: \>500 (milliseconds \[msec\]); change from SS4 baseline \>30 msec and change from SS4 baseline \>60 msec. QT interval corrected using Fridericia's formula (QTcF) (msec): \>=450 (male) or \>=470 (female) msec; change from SS4 baseline \>30 msec; change from SS4 baseline \>60 msec. PR interval (msec): \>230 msec. Only those ECG parameters in which at least 1 participant in any of the reporting arm had markedly abnormal criteria are reported in this outcome measure. SS4 Baseline was defined as the last non-missing measurement taken up to the date of first dose in the SS4.
Time frame: Baseline, Weeks 52, and 104 of SS4
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), TEAEs by Severity and Treatment Related TEAEs: SS3
AE: any untoward medical occurrence that did not necessarily have a causal relationship with treatment. SAE: an AE that met one of the following criteria: resulted in death; was life-threatening; required inpatient or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect or medically significant. AEs were graded by the National Cancer Institute Common Terminology Criteria for AE version 5 where, Grade(G) 1: mild AE; G2: moderate; G3: severe; G4: life-threatening consequences, urgent intervention indicated; G5: death related to AE. AE was considered TEAE if it started or worsened in severity on or after the first dose of study treatment. Treatment related AEs were AEs that were related to the study treatment and relatedness was judged by investigator.
Time frame: From first dose of study treatment (Day 1) up to 4 weeks post last dose of study treatment (maximum treatment exposure: 38 weeks; maximum follow-up: 42 weeks)
Number of Participants With TEAEs of Special Interest: SS3
The TEAEs of special interest included: cardiovascular events (bradycardia, atrioventricular \[AV\] conduction delay, and hypertension); macular edema; pulmonary disorders (airflow obstruction \[forced expiratory volume in 1 second, and forced vital capacity\], decreased gas exchange \[diffusing capacity of the lung for carbon monoxide\]); infections (severe infections, opportunistic infections, and herpes simplex and herpes zoster); liver injury (liver transaminases elevation, and bilirubin elevation); posterior reversible encephalopathy syndrome; and malignancies. Number of participants with any TEAEs of special interest were reported in this outcome measure.
Time frame: From first dose of study treatment (Day 1) up to 4 weeks post last dose of study treatment (maximum treatment exposure: 38 weeks; maximum follow-up: 42 weeks)
Number of Participants With Clinically Meaningful Changes in Laboratory Parameters: SS3
Clinically meaningful laboratory abnormalities:Hemoglobin, Hematocrit, Erythrocytes (\<0.8\*LLN); Ery. Volume, Hemoglobin,Mean Corpuscular HGB Concentration \<0.8\*LLN or \>1.5\*LLN;Reticulocytes, Leukocytes, Lymphocytes, Neutrophils, Neutrophils, Basophils, Eosinophils, Monocytes (\>1.2\*ULN), Prothrombin Time(\>1.1\*ULN).Clinical Chemistry: Bilirubin, Direct Bilirubin, Indirect Bilirubin (1.5\*ULN), Aspartate Aminotransferase, Alanine Aminotransferase, Gamma Glutamyl Transferase, Alkaline Phosphatase (\>3.0\*ULN); Albumin, Urate (\<0.8\*LLN and \>1.2\*ULN; Urea Nitrogen,Creatinine Cholesterol \>1.3\*ULN; Cholesterol \<0.8\*LLN or \>1.2\*LLN, Triglycerides,Potassium,Calcium \< 0.9x LLN \& \>1.1x ULN; Bicarbonate, Glucose, Creatine Kinase. Urinalysis: Glucose, Ketones, Protein, Hemoglobin, Urobilinogen, Bilirubin, Nitrite \>=1; Leukocyte Erythrocytes, Leukocytes \>=20; Epithelial Cells\>=6, Hyaline Cast\>1; Bacteria\>20. Number of participants with any laboratory abnormality meeting specified criteria is included.
Time frame: From first dose of study treatment (Day 1) up to 4 weeks post last dose of study treatment (maximum treatment exposure: 38 weeks; maximum follow-up: 42 weeks)
Number of Participants With TEAEs, SAEs, TEAEs by Severity and Treatment Related TEAEs: SS4
AE: any untoward medical occurrence that did not necessarily have a causal relationship with treatment. SAE: an AE that met one of the following criteria: resulted in death; was life-threatening; required inpatient or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect or medically significant. AEs were graded by the National Cancer Institute Common Terminology Criteria for AE version 5 where, G1: mild AE; G2: moderate; G3: severe; G4: life-threatening consequences, urgent intervention indicated; G5: death related to AE. AE was considered TEAE if it started or worsened in severity on or after the first dose of study treatment. Treatment related AEs were AEs that were related to the study treatment and relatedness was judged by investigator.
Time frame: From first dose of study treatment (Day 1) up to 4 weeks post last dose of study treatment (maximum treatment exposure: 166.3 weeks; maximum follow-up: 170.3 weeks)
Number of Participants With TEAEs of Special Interest: SS4
The TEAEs of special interest included: cardiovascular events (bradycardia, AV conduction delay, and hypertension); macular edema; pulmonary disorders (airflow obstruction \[forced expiratory volume in 1 second, and forced vital capacity\], decreased gas exchange \[diffusing capacity of the lung for carbon monoxide\]); infections (severe infections, opportunistic infections, and herpes simplex and herpes zoster); liver injury (liver transaminases elevation, and bilirubin elevation); posterior reversible encephalopathy syndrome; and malignancies. Number of participants with any TEAEs of special interest were reported in this outcome measure.
Time frame: From first dose of study treatment (Day 1) up to 4 weeks post last dose of study treatment (maximum treatment exposure: 166.3 weeks; maximum follow-up: 170.3 weeks)
Number of Participants With Clinically Meaningful Changes in Laboratory Parameters: SS4
Clinically meaningful laboratory abnormalities:Hemoglobin, Hematocrit, Erythrocytes (\<0.8\*LLN); Ery. Volume, Hemoglobin,Mean Corpuscular HGB Concentration \<0.8\*LLN or \>1.5\*LLN;Reticulocytes, Leukocytes, Lymphocytes, Neutrophils, Neutrophils, Basophils, Eosinophils, Monocytes (\>1.2\*ULN), Prothrombin Time(\>1.1\*ULN).Clinical Chemistry: Bilirubin, Direct Bilirubin, Indirect Bilirubin (1.5\*ULN), Aspartate Aminotransferase, Alanine Aminotransferase, Gamma Glutamyl Transferase, Alkaline Phosphatase (\>3.0\*ULN); Albumin, Urate (\<0.8\*LLN and \>1.2\*ULN; Urea Nitrogen,Creatinine Cholesterol \>1.3\*ULN; Cholesterol \<0.8\*LLN or \>1.2\*LLN, Triglycerides,Potassium,Calcium \< 0.9x LLN \& \>1.1x ULN; Bicarbonate, Glucose, Creatine Kinase. Urinalysis: Glucose, Ketones, Protein, Hemoglobin, Urobilinogen, Bilirubin, Nitrite \>=1; Leukocyte Erythrocytes, Leukocytes \>=20; Epithelial Cells\>=6, Hyaline Cast\>1; Bacteria\>20. Number of participants with any laboratory abnormality meeting specified criteria is included.
Time frame: From first dose of study treatment (Day 1) up to 4 weeks post last dose of study treatment (maximum treatment exposure: 166.3 weeks; maximum follow-up: 170.3 weeks)
Number of Participants According to Markedly Abnormal Criteria for Vital Signs: SS4
Pre-defined markedly abnormal criteria for vital signs included: Systolic blood pressure (millimeters of mercury \[mmHg\]): low: \<=90 mmHg and high: \>150 mmHg. Diastolic blood pressure (mmHg): low: \<=50 mmHg and high: \>90 mmHg. Heart rate (beats per minute \[bpm\]): low: \<40 bpm, \<50 bpm and high: \>100 bpm. Only those vital signs parameters in which at least 1 participant in any of the reporting arm had markedly abnormal criteria are reported in this outcome measure. SS4 baseline=the last non-missing measurement taken up to the date of first dose in the SS4.
Time frame: Baseline, Weeks 1, 12, 24, 36, 52, 64, 76, 88 and 104 of SS4
Percentage of Participants With Clinical Remission by CDAI at Weeks 12, 24, 36, 52, 64, 76, 88 and 104: SS4
Clinical remission was considered as CDAI score \<150. CDAI was a composite index consisting of a weighted scoring of 8 disease activity variables: number of liquid or soft stools; extent of abdominal pain graded from 0 (none) to 3 (severe); general well-being rating assessed from 0 (generally well) to 4 (terrible); presence of complications; taking diphenoxylate/atropine, loperamide or opiates for diarrhea; presence of an abdominal mass (0 as none, 2 as questionable, 5 as definite); HCT 47 in men and 42 in women and percentage deviation from standard weight, lower bound -10. Total CDAI score was calculated as the sum of variable scores\*weighting factor and ranged from 0 (no disease) to 600 (severe disease), where higher scores indicated more severe disease.
Time frame: Weeks 12, 24, 36, 52, 64, 76, 88 and 104 of SS4
Percentage of Participants With Clinical Response by CDAI at Weeks 12, 24, 36, 52, 64, 76, 88 and 104: SS4
Clinical Response was defined as having clinical remission CDAI or \>=100-point decrease from baseline in CDAI score where, clinical remission was considered as CDAI \<150. CDAI was a composite index consisting of a weighted scoring of 8 disease activity variables: number of liquid or soft stools; extent of abdominal pain graded from 0 (none) to 3 (severe); general well-being rating assessed from 0 (generally well) to 4 (terrible); presence of complications; taking diphenoxylate/atropine, loperamide or opiates for diarrhea; presence of an abdominal mass (0 as none, 2 as questionable, 5 as definite); HCT 47 in men and 42 in women and percentage deviation from standard weight, lower bound -10. Total CDAI score was calculated as the sum of variable scores\*weighting factor and ranged from 0 (no disease) to 600 (severe disease), where higher scores indicated more severe disease.
Time frame: Weeks 12, 24, 36, 52, 64, 76, 88 and 104 of SS4
Percentage of Participants With Clinical Remission by PRO2 at Weeks 12, 24, 36, 52, 64, 76, 88 and 104: SS4
Clinical remission was defined as PRO2 score \<8. The PRO2 was a patient-reported outcome measure based on abdominal pain and stool frequency components of the CDAI. The abdominal pain rating was graded from 0 (none) to 3 (severe) each day for 7 days. The stool frequency was defined as number of liquid or soft stools each day for 7 days. Total PRO2 score was calculated as the sum of averaged abdominal pain/stool frequency variable scores\*weighting factor. The PRO2 score had a minimum score of 0 and had no upper bound, with a higher score indicating more frequent stools and more severe abdominal pain.
Time frame: Weeks 12, 24, 36, 52, 64, 76, 88 and 104 of SS4