Multicenter Study of Oral Ozanimod as Maintenance Therapy in patients with Moderately to Severely Active Crohn's Disease

Prior treatment

• Subject has current or planned treatment with immunomodulatory agents (eg, AZA, 6-MP, or MTX) during the Maintenance Study.
• Subject has chronic nonsteroidal anti-inflammatory drug (NSAID) use (note: occasional use of NSAIDs and acetaminophen [eg, headache, arthritis, myalgias, or menstrual cramps] and aspirin up to 325 mg/day is permitted).
• Subject has received previous treatment with D-penicillamine, leflunomide or thalidomide within 8 weeks of first dose of IP in Induction.
• Subject has received previous treatment with natalizumab, fingolimod, or other S1P modulators.
• Subject has received previous treatment with cyclosporine, tacrolimus, sirolimus, or mycophenolate mofetil within 16 weeks of initiation of Induction Screening.
• Subject has a history of treatment with intravenous immunoglobulin (IVIg) or plasmapheresis, within 3 months prior to first dose of IP in Induction.
• Subject is receiving treatment with breast cancer resistance protein (BCRP) inhibitors (eg, cyclosporine, eltrombopag)
• Subject is receiving treatment with any of the following drugs or interventions a. CYP2C8 inducers (eg, rifampicin) b. Monoamine oxidase inhibitors (eg, selegiline, phenelzine)
• Subject has received treatment with Class Ia or Class III antiarrhythmic drugs, treatment with 2 or more agents in combination known to prolong PR interval or treatment with additional prohibited systemic cardiac medication provided in Table 7.
• Subject has received a live or live attenuated vaccine within 4 weeks prior to first dose of IP in this study.
• Subject is pregnant, lactating, or has a positive urine beta human chorionic gonadotropin (β-hCG) test measured prior to randomization.
• Subject has received any of the following therapies during the Induction Study: a. rectal steroid therapy (ie, steroids administered to the rectum or sigmoid via foam or enema) b. post-baseline (of induction) initiation of, or increase in, corticosteroids to treat worsening CD to a dose greater than the maximum daily dose taken between the screening and baseline visits c. rectal 5- aminosalicylates (ASA) (ie, 5-ASA administered to the rectum) d. parenteral corticosteroids > 14 days e. total parenteral nutrition therapy f. antibiotics for the treatment of CD g. immunomodulatory agents (6-MP, AZA, including but not limited to cyclosporine, mycophenolate mofetil, tacrolimus, and sirolimus) h. immunomodulatory biologic agents as well as other treatments for CD such as etrasimod, filgotinib, and upadacitinib i. investigational agents j. apheresis

Other illness

• Subject has any clinically relevant cardiovascular, hepatic, neurological, pulmonary (severe respiratory disease [pulmonary fibrosis or chronic obstructive pulmonary disease]), ophthalmological, endocrine, psychiatric, or other major systemic disease making implementation of the protocol or interpretation of the study difficult or that would put the subject at risk by participating in the study.
• Subject has undergone a colectomy (partial or total), small bowel resection, or an ostomy (ie, temporary colostomy, permanent colostomy, ileostomy, or other enterostomy) since Day 1 of the Induction Studies or has developed symptomatic fistula (enterocutaneous or entero enteral).
• Subject has had cancer within 5 years including solid tumors and hematological malignancies (except basal cell and in situ squamous cell carcinomas of the skin or cervical dysplasia/cancer that have been excised and resolved); or colonic dysplasia that has not been completely removed.
• Hypersensitivity to active ingredients or excipients of ozanimod or placebo

Lab values

• Subject has received previous treatment with lymphocyte-depleting therapies (eg, Campath™, anti-CD4, cladribine, rituximab, ocrelizumab, cyclophosphamide, mitoxantrone, total body irradiation, bone marrow transplantation, alemtuzumab, or daclizumab).

Other

• Subjects who have met the discontinuation criteria in the Induction Period
• Subject has any clinically significant abnormal results (eg, labs or ECG) which, in the opinion of the investigator, may put the subject at risk.
• Subject has suspected or diagnosed intra-abdominal or perianal abscess that has not been appropriately treated.

• Subject fulfilled the inclusion criteria at time of entry into the Induction Study (RPC01 3201 or RPC01-3202) and has completed the Week 12 efficacy assessments of the Induction Study.
• Subject should not have any constraints under local regulations, must provide written informed consent prior to any study-related procedures, and must have the ability to comply with the Table of Events.
• Subject is in clinical response (a reduction from baseline in CDAI of ≥ 100 points or CDAI score of < 150 points) and/or clinical remission (CDAI score of < 150 points) and/or has an average daily stool frequency score ≤ 3 and an average abdominal pain score ≤ 1 with abdominal pain and stool frequency no worse than baseline at Week 12 of the Induction Study.
• Female subjects of childbearing potential (FCBP) must agree to practice a highly effective method of contraception throughout the study until completion of the 90-day Safety Follow-up Visit. Examples of acceptable methods of birth control in the study are the following: a) combined hormonal (containing oestrogen and progestogen) contraception, which may be oral, intravaginal, or transdermal b) progestogen-only hormonal contraception associated with inhibition of ovulation, which may be oral, injectable, or implantable c) placement of an intrauterine device (IUD) d) placement of an intrauterine hormone-releasing system (IUS) e) bilateral tubal occlusion f) vasectomized partner g) complete sexual abstinence