Moderately to Severely Active Ulcerative Colitis MedDRA version: 20.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 10017947 - Gastrointestinal disorders
Conditions
Sponsors
Celgene International II Sàrl
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age = 2 and < 17 years of age, inclusive, (for the assigned cohort) at the time of informed consent/assent. Note: Subjects with a weight below the 5 th percentile for age, should be discussed with the Medical Monitor prior to enrollment. 2. One or both parent(s) or legal guardian(s) understands and voluntarily signs informed consent prior to any study-related assessments or procedures (as required by national or local regulations). - Assent from subjects will also be obtained in an age-appropriate manner in conjunction with applicable local regulations. Written assent templates, appropriate for relevant age ranges, will be made available to clinical study sites. 3. Willing and able to adhere to the study visit schedule and other protocol requirements including swallowing a capsule (until a sprinkle formulation of ozanimod is available as described in Section 7.1). 4. Have had UC diagnosed prior to the Screening Visit. The diagnosis should be confirmed by clinical and endoscopic evidence and corroborated by a histopathology report (note: histopathology may be performed during endoscopy at Screening if no prior report is readily available). 5. Evidence of UC extending beyond the rectum, as determined by baseline endoscopy (flexible sigmoidoscopy or colonoscopy) 6. Has moderately to severely active UC, defined as a 4-component Mayo Score = 6 and = 12 at the time of screening and day 1, including the following: Mayo Endoscopy Subscore = 2, Rectal Bleeding Score = 1, and Stool Frequency Score = 1. 7. Has had an inadequate response, loss of response to, or is intolerant to at least 1 of the following treatments for UC (Appendix B): a. oral aminosalicylates (eg, mesalamine, sulfasalazine, olsalazine, balsalazide) (N/A in France) b. systemic corticosteroids (eg, oral prednisone, budesonide MMX, IV corticosteroids) c. immunomodulators (eg, AZA, 6-MP, cyclosporine, MTX) d. biologic therapy (eg, abatacept, infliximab, etanercept, adalimumab, anakinra, rituximab, vedolizumab, and golimumab) e. other systemic immunomodulatory treatments for UC, such as tofacitinib Note: criterion 7b-7e are N/A in Germany 8. Subjects may concurrently receive treatment with oral 5-ASAs, or with prednisone or equivalent (= 0.5 mg/kg/ day up to 20 mg/day) or beclomethasone < 5mg/day - If on oral 5-ASAs, the dose must have been stable for at least 3 weeks prior to screening endoscopy = baseline . - If on corticosteroids, the dose must have been stable for at least 2 weeks prior to screening endoscopy and must remain stable through the first 5 weeks of treatment (ie, until the Week 5 study visit). -If discontinuing corticosteroids (e.g. MMX), subject must taper as described in Section 8.1.1. 9. Inclusion criterion 9 is not applicable for protocol amendment 2.0. 10. Must have documentation of vaccinations per standard immunization schedule including complete Varicella vaccination at least 30 days prior to randomization. (VZV and IgG +ve) 11. Females of childbearing potential (FCBP)1 must agree to practice a highly effective method of contraception2 throughout the study until completion of the 90-day Safety Follow-up Visit. Highly effective methods of contraception are those that alone or in combination result in a failure rate of a Pearl index of less than 1% per year when used consistently and correctly. Selection of contraceptive methods should be based on those available/approved as per national or local practice. Acceptable methods of bir
Exclusion criteria
Exclusion criteria: Cardiovascular, hepatic, neurological, pulmonary, 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 Crohn’s disease, indeterminate colitis or the presence or history of a fistula consistent with Crohn’s disease or microscopic colitis, radiation colitis or ischemic colitis +ve for toxin producing Clostridium difficile or PCR exam of stool. If +ve, subjects may be rescreened after appropriate treatment and retested no earlier than 7 days after treatment completion +ve examination for pathogens. If positive, subjects may be treated and rescreened History of treatment with topical rectal 5-aminosalicylic acid or topical rectal steroids within 2 weeks of Screening endoscopy or anti-motility medications Apheresis within 2 weeks of randomization Delayed growth or pubertal development and who will not maintain a stable dose of corticosteroids through Week 5 Pregnancy (also on day 1), lactation, or positive serum ß-hCG during Screening History or presence of: Structural cardiac disease, Cardiac events or diseases that predispose to cardiac complications, Prolonged QT interval corrected for heart rate using Fridericia’s formula>450 msec for both genders, or additional risk for QT interval prolongation, resting HR 9%) or is a diabetic subject with significant comorbid conditions History of uveitis within the last year prior or at Screening, or history or evidence of retinal disease Subject has any known active bacterial, viral, fungal, mycobacterial infection, or any major episode infection that required hospitalization or treatment with intravenous antibiotics within 30 days of Screening or oral antibiotics within 14 days of screening In the case of prior SARS-CoV-2 infection, symptoms must be resolved and based on Investigator assessment, there are no sequelae that would place the subject at a higher risk of receiving investigational treatment Recurrent or chronic infection, recurrent urinary tract infections are allowed, there should also be documented evidence of surveillance for dysplasia for all subjects with left-sided colitis of > 12 years’ duration and total or extensive colitis of > 8 years’ duration. History of cancer History of or currently active primary or secondary immunodeficiency, or subjects with known genetic disorders as a cause for colitis ECG showing clinically significant abnormality Serum creatinine > 1.4 mg/dL for females, or > 1.6 mg/dL for males Liver function impairment; or, persisting elevations of alanine aminotransferase or aspartate aminotransferase > 2x upper limit of normal; or direct bilirubin > 1.5x UL Platelet < 100,000/µL Hemoglobin 7 < 8 g/dL Neutrophil < 1500/µL Absolute white blood < 3500/µL ALC < 800/µL Stool positive for pathogens Pulmonary function test measurements: Forced expiratory volume at 1 second or a forced vital capacity < 70% of predicted values, Hypersensitivity to active ingredients or excipients of ozanimod Treated with biological or investigational agent, including for SARS-CoV-2, within 4 weeks of that agent prior to the first dose of IP. Undetect
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of ozanimod in pediatric subjects with moderately to severely active UC (3-component Mayo Score: clinical remission, Week 52);Secondary Objective: Evaluate the efficacy of ozanimod in pediatric subjects with moderately to severely active UC (3-component Mayo Score: clinical remission, Week 10) Evaluate the efficacy of ozanimod in pediatric subjects with moderately to severely active UC (3-component Mayo Score: clinical response, Week 52) Evaluate the efficacy of ozanimod in pediatric subjects with moderately to severely active UC (3-component Mayo Score: clinical response, Week 10) Evaluate symptomatic remission Evaluate time to achieve symptomatic remission Evaluate endoscopic improvement by Mayo Endoscopy Score Evaluate corticosteroid-free remission Evaluate the safety and tolerability of 2 doses of ozanimod in pediatric subjects w/moderately-severely active UC Characterize the pharmacokinetics of 2 doses of ozanimod and its major active metabolites in pediatric subjects with moderately-severely active UC Evaluate the pharmacodynamic effects of 2doses of ozanimod in pediatric subjects w/moderately-severely active UC;Primary end point(s): Proportion of subjects who achieve clinical remission, defined as all the following: •Mayo Endoscopy Subscore (MES) = 1 •Rectal Bleeding Subscore (RBS) = 0 •Stool Frequency Subscore (SFS) = 1, with a decrease of = 1 point from Baseline SFS ;Timepoint(s) of evaluation of this end point: Week 52 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1/Proportion of subjects who achieve clinical response defined as all the following: • Decrease from Baseline in the 3-component Mayo score of at least 2 points and at least 35% • Decrease in RBS of at least 1 point OR absolute RBS = 1 2/Proportion of subjects who achieve clinical remission defined as all the following: • MES = 1 • RBS = 0 • SFS = 1, with a decrease of =1 point from Baseline SFS 3/Proportion of subjects who achieve symptomatic improvement of UC, defined as all the following: • RBS = 0 • SFS = 1 • Decrease in SFS of = 1 from Baseline 4/Proportion of subjects who achieve endoscopic improvement, defined as MES = 1 5/Proportion of subjects who achieve corticosteroid-free remission at Week 52, defined as all the following: • Did not receive steroids for = 12 weeks prior to Week 52 • Achieved clinical remission defined by the 3-component Mayo score 6/Secondary – Safety and Tolerability Number and proportion of subjects experiencing AEs, SAEs, AEs leading to discontinuation from treatment, and AEs of interest (AEIs) 7/Secondary - Pharmacokinetics Steady state systemic exposure of ozanimod and CC112273 8/Secondary – Pharmacodynamics Absolute and percent change from baseline in ALC ;Timepoint(s) of evaluation of this end point: 1/Week 10 and week 52 2/Week 10 3/Week 10 and week 52 4/Week 10 and week 52 5/Week 52 6/throughout the study 7/Week 18 and throughout the study 8/Week 10 and week 52 | — |
Countries
Belgium, Canada, France, Germany, Israel, Japan, Netherlands, Poland, Russian Federation, Spain, United Kingdom, United States
Contacts
Public ContactGSM-CT
Bristol-Myers-Squibb International Corporation
Outcome results
None listed