Induction Study #1 of Oral Ozanimod as Induction Therapy for Moderately to Severely Active Crohn's Disease

Crohn's Disease Activity Index (CDAI) is a composite score used to measure the clinical activity of Crohn's disease. CDAI uses 8 variables: number of soft/liquid stools, severity of abdominal pain (0=none to 3=severe), general well-being (0=well to 4=terrible), presence of complications, need for antidiarrheal drugs, presence of abdominal mass, hematocrit, and change in body weight. Scores for stool number, abdominal pain, and well-being are summed over the 7 days before each visit. The other factors are also recorded and weighted to create a total CDAI score, which ranges from 0-600, with higher scores indicating worse disease (score 150-219 = mild, 220-450 = moderate, \>450 = severe). This measure reports the percentage of participants whose CDAI score was below 150 at 12 weeks.

Time frame: At Week 12

Population: Intent to treat population consist of all randomized participants that received at least 1 dose of investigational drug

This measure evaluated improvement in gut inflammation at 12 wks using Global Histologic Activity Score (GHAS). GHAS was assessed for each ileal & colonic segment (ileum, right colon, transverse colon, left colon-descending/sigmoid colon & rectum). Segment subscores were calculated by adding scores for epithelial damage/tissue changes(0-2), cellular infiltration for mononuclear & polymorphonuclear cells(0-2 each), presence of certain cells(0-3) & erosion, ulcers, granulomas(0 or 1). GHAS score within each segment ranged from 0-16 & across five segments ranged from 0-80. Higher scores indicated more inflammation. Responders with histologic remission was defined as GHAS score ≤8 (each segment) \[meeting criteria: epithelial damage(0), architectural changes(0-2), mononuclear cell infiltration(0-2), polymorphonuclear cell infiltration(0), polymorphonuclear cells in epithelium(0), erosion/ulcers(0), granuloma(0-1) & affected biopsy specimens(0-3)\] & ≤40 (across all segments).

Time frame: At Week 12

Population: Intent to treat population consist of all randomized participants that received at least 1 dose of investigational drug

This measure shows the percentage of participants have no longer any large ulcers (bigger than 0.5 cm) in their gut and in any section of the gut, less than 10% of the surface has ulcers at 12 weeks. This helps to understand how well the treatment is healing the gut and reducing ulceration.

Time frame: At Week 12

Population: Intent to treat population consist of all randomized participants that received at least 1 dose of investigational drug

CDEIS is an index used to determine Crohn's disease severity by endoscopic exam of the ileum and colon. The intestine is divided into 5 segments: rectum, sigmoid/left colon, transverse colon, right colon, and ileum. In each segment, four variables are assessed: deep ulceration, superficial ulceration, percentage of ulcerated surface, and percentage of surface affected by Crohn's disease, using 10-cm visual analogue scales. The presence of ulcerated and nonulcerated stenosis is also evaluated across the entire intestine. These factors are weighted and summed for a total score from 0-44, with higher scores indicating more severe disease. This measure reports the percentage of participants whose CDEIS score improved by at least 50% at 12 weeks, based on endoscopic exam.

Time frame: At Week 12

Population: Intent to treat population consist of all randomized participants that received at least 1 dose of investigational drug

This measure reports the percentage of participants whose Crohn's disease symptoms and gut inflammation improved at 12 weeks. It includes those with mild or no belly pain (score ≤1), no more than three bowel movements per day (score ≤3), and no worsening from baseline. It also includes participants whose gut inflammation, measured by SES-CD, was low (score ≤4) and improved by at least 2 points. SES-CD assesses inflammation based on four components: size of ulcers, ulcerated surface, affected surface, and presence of narrowing, each scored from 0 (none) to 3 (severe) across five segments (ileum, right colon, transverse colon, left colon, rectum). The total SES-CD score ranges from 0-12 per segment and 0-60 overall, with higher scores indicating greater inflammation.

Time frame: At Week 12

Population: Intent to treat population consist of all randomized participants that received at least 1 dose of investigational drug

This measure reports the percentage of participants whose Crohn's disease symptoms and gut inflammation improved at 12 weeks. It includes those with mild or no belly pain (score ≤1), no more than three bowel movements per day (score ≤3), and no worsening from baseline. It also includes participants whose gut inflammation, measured by SES-CD, improved by at least 50% from baseline. SES-CD assesses inflammation based on four components: size of ulcers, ulcerated surface, affected surface, and presence of narrowing, each scored from 0 (none) to 3 (severe): score ranges from 0-12 across four components and 0-60 overall across five segments (ileum, right colon, transverse colon, left colon, rectum). The total higher SES-CD score indicating greater inflammation.

Time frame: At Week 12

Population: Intent to treat population consist of all randomized participants that received at least 1 dose of investigational drug

The Simple Endoscopic Score for Crohn's Disease (SES-CD) is used to assess the degree of inflammation in patients with Crohn's disease. The SES-CD evaluates four components-size of ulcers, ulcerated surface, affected surface, and presence of narrowing-each scored from 0 (none) to 3 (severe): score ranges from 0-12 across four components and 0-60 overall across five segments (ileum, right colon, transverse colon, left colon, rectum). The total higher SES-CD score indicating greater inflammation. Baseline is defined as the last assessment prior to the first drug administration (based on the time of measurement, if available; otherwise, the last assessment prior to or on the date of first drug administration). This measure reports the percentage of participants whose SES-CD score improved by 50% or more from baseline to Week 12.

Time frame: At Week 12

Population: Intent to treat population consist of all randomized participants that received at least 1 dose of investigational drug

Abdominal pain (AP) and stool frequency (SF) clinical remission was defined as an average daily abdominal pain score ≤1 and average daily stool frequency ≤3, with AP and SF no worse than baseline at Week 12. AP was graded on a scale from 0 (none) to 3 (severe), and SF was defined as the number of liquid or soft stools per day. This measure reports the percentage of participants who, by Week 12, had low abdominal pain (score ≤1) and three or fewer bowel movements per day, without worsening symptoms compared to when they started the study. Participants began using the diary at the first visit and continued throughout the study.

Time frame: At Week 12

Population: Intent to treat population consist of all randomized participants that received at least 1 dose of investigational drug

The Crohn's Disease Activity Index (CDAI) is a composite score used to measure clinical activity in Crohn's disease. CDAI is based on 8 variables: number of soft/liquid stools, severity of abdominal pain (0 \[none\] to 3 \[severe\]), general well-being (0 \[well\] to 4 \[terrible\]), presence of complications, use of antidiarrheal drugs, abdominal mass, hematocrit, and deviation in body weight. Scores for stool frequency, pain, and well-being are summed over 7 days prior to each visit. The total CDAI score ranges from 0-600, with higher scores indicating worse disease activity (score 150-219 = mild, 220-450 = moderate, \>450 = severe). This measure reports the percentage of participants whose Crohn's disease improved at 12 weeks, defined as a CDAI decrease of at least 100 points or a score below 150, along with at least a 50% reduction in intestinal inflammation (SES-CD score).

Time frame: At Week 12

Population: Intent to treat population consist of all randomized participants that received at least 1 dose of investigational drug

The Crohn's Disease Activity Index (CDAI) is a composite score used to measure the clinical activity of Crohn's disease. CDAI is calculated using 8 variables: number of soft/liquid stools, severity of abdominal pain (0 \[none\] to 3 \[severe\]), general well-being (0 \[well\] to 4 \[terrible\]), presence of complications, use of antidiarrheal drugs, presence of an abdominal mass, hematocrit, and deviation in body weight. Scores for stool frequency, pain, and well-being are summed over the 7 days prior to each visit. The remaining variables are also weighted and included in the total CDAI score, which ranges from 0-600, with higher scores indicating worse disease activity (score 150-219 = mild, 220-450 = moderate, \>450 = severe). This measure reports the percentage of participants whose CDAI score improved by at least 100 points, or was below 150, at 12 weeks.

Time frame: At Week 12

Population: Intent to treat population consist of all randomized participants that received at least 1 dose of investigational drug

This measure reports the percentage of participants whose Crohn's disease symptoms improved meaningfully after 12 weeks of treatment, defined as a decrease of at least 70 points in their Crohn's Disease Activity Index (CDAI) score from baseline. The CDAI is a composite score used to assess clinical activity in Crohn's disease, based on 8 variables: number of soft/liquid stools, severity of abdominal pain (0 \[none\] to 3 \[severe\]), general well-being (0 \[well\] to 4 \[terrible\]), presence of complications, use of antidiarrheal drugs, presence of an abdominal mass, hematocrit, and deviation in body weight. Scores for stool frequency, pain, and well-being are summed over 7 days prior to each visit. The total CDAI score ranges from 0-600, with higher scores indicating more severe disease (score 150-219 = mild, 220-450 = moderate, \>450 = severe).

Time frame: At Week 12

Population: Intent to treat population consist of all randomized participants that received at least 1 dose of investigational drug

This endpoint measured the percentage of participants who achieved both clinical remission and significant endoscopic improvement at Week 12. Clinical remission was defined as a Crohn's Disease Activity Index (CDAI) score of less than 150 at Week 12. Endoscopic improvement was defined as a decrease of at least 50% from baseline in the Simple Endoscopic Score for Crohn's Disease (SES-CD) at Week 12. The CDAI was a composite score assessing disease activity based on symptoms and laboratory values, while the SES-CD evaluated endoscopic findings in the intestinal mucosa. Achieving both criteria indicated substantial improvement in both symptoms and intestinal inflammation.

Time frame: At Week 12

Population: Intent to treat population consist of all randomized participants that received at least 1 dose of investigational drug