YELLOWSTONE – Induction Study (RPC01-3201 and 3202) – A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of Oral Ozanimod as Induction Therapy for Moderately to Severely Active Crohn’s Disease

Purpose of this study?

To evaluate the safety and effectiveness of an oral investigational drug (ozanimod) which is taken once daily. 

Inclusion Criteria:

• are 18 to 75 years of age
• have been diagnosed with active Crohn's disease confirmed by endoscopy (a procedure where a doctor looks inside your digestive tract using a device called an endoscope)
• currently have symptoms associated with moderately to severely active Crohn's disease, and
• have not improved on or have not been able to tolerate, at least one prior Crohn's disease medication†
• †Eligible prior medications include corticosteroids, immunomodulators or biologic therapy (e.g., ustekinumab, TNFα antagonists or vedolizumab).

Exclusion Criteria:

• Diagnosis of ulcerative colitis, indeterminate colitis, radiation colitis, or ischemic colitis or known strictures or stenosis leading to symptoms of obstruction
• Current stoma, connection of your ileal and anal pouch, symptomatic fistula, or need for ileostomy or colostomy *Other inclusion/exclusion criteria apply     

Primary outcome measures:

Proportion of participants with a Crohn's Disease Activity Index (CDAI) score < 150 [ Time Frame: Week 12 ]

Secondary outcome measures:

1. Proportion of participants with average daily abdominal pain score ≤ 1 point, and average daily stool frequency score ≤ 3 points with abdominal pain and stool frequency no worse than baseline [ Time Frame: Week 12 ]
2. Proportion of participants with a Simple Endoscopic Score for Crohn's Disease (SES-CD) score decrease from baseline of ≥ 50% [ Time Frame: Week 12 ]
3. Proportion of participants with CDAI reduction from baseline of ≥ 100 points or CDAI score < 150 [ Time Frame: Week 12 ]
4. Proportion of participants with CDAI reduction from baseline of ≥ 100 points or CDAI score < 150 and SES-CD decrease from baseline of ≥ 50% [ Time Frame: Week 12 ]
5. Proportion of participants with CDAI score < 150 and SES-CD decrease from baseline of ≥ 50% [ Time Frame: Week 12 ]
6. Proportion of participants with an average daily abdominal pain score ≤ 1 point, and average daily stool frequency score ≤ 3 points and both no worse than baseline AND an SES-CD ≤ 4 points and decrease ≥2 points [ Time Frame: Week 12 ]
7. Proportion of participants with an average daily abdominal pain score ≤ 1 point, and average daily stool frequency score ≤ 3 points and both no worse than baseline AND an SES-CD decrease from baseline of ≥ 50% [ Time Frame: Week 12 ]
8. Histologic Improvement based on differences between ozanimod and placebo in histologic disease activity scores (ie, Global Histologic Disease Activity Score changes) [ Time Frame: Week 12 ]
9. Proportion of participants with CDAI reduction from baseline of ≥ 70 points [ Time Frame: Week 12 ]
10. Proportion of participants with absence of ulcers ≥ 0.5 cm with no segment with any ulcerated surface ≥ 10% [ Time Frame: Week 12 ]
11. Proportion of participants with a Crohn's Disease Endoscopic Index of Severity (CDEIS) decrease from baseline of ≥ 50% [ Time Frame: Week 12 ]

Study Locations in Europe:

Austria, Belgium, Bosnia and Herzegovina, Bulgaria, Croatia, Czechia, Denmark, Finland, France, Germany, Ireland, Italy, Latvia, Moldova, Norway, Poland, Romania, Spain, Switzerland, Ukraine, UK

Estimated Study Completion Date: September 25, 2023

Further information on clinicaltrial.gov with trial numbers NCT03440372 & NCT03440385