Trial Outcomes & Findings for A Study Evaluating the Efficacy and Safety of Oral Etrasimod in the Treatment of Adult Participants With Moderately to Severely Active Crohn's Disease (NCT NCT04173273)

379 participants (84 in sub-study A \[SSA\]; 295 in SS1) enrolled. Participants who completed treatment and met study specific criteria in SS1 eligible for SS3. Participants from SS3 and SSA who completed at least 52 and 66 weeks of treatment, respectively eligible for SS4. Sub-studies planned: SSA, SS1, SS2, SS3 and SS4. The study (including SS3 and SS4) terminated early due to insufficient induction treatment benefit of etrasimod as observed in SS1. SS2 not initiated; its results not reported.

SS3 had responder cohort (RC) and non-responder cohort (NRC). Participants at and after Week 6 of SS3 in RC were assessed for loss of response (LOR) defined as Crohn's Disease Activity Index (CDAI) score \>=220 and \>=100-point increase from maintenance first dose (MFD) visit. As pre-planned participants from RC who had LOR were summarized in RC till the confirmed LOR visit and data after LOR was summarized under NRC along with participants in NRC from start of SS3 for safety analysis.

Here, "Number Analyzed" signifies number of participants evaluable for the specified sub study.

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.

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.

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.

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.

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.

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.

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.

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.

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.

The plasma concentration of etrasimod at 4 hours post-dose has been reported in this outcome measure.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.