Evaluation of Ozanimod Efficacy and Safety in Pediatric Patients with Moderate to Severe Crohn's Disease Unresponsive to Conventional Therapy
- Trial ID
- 2023-508777-91-00
- Protocol
- IM047-023
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **efficacy** of **ozanimod** administered once daily in pediatric participants with moderately to severely active **Crohn's Disease** (CD). The study aims to assess clinical remission by the Pediatric Crohn's Disease Activity Index (PCDAI) at Week 64 and to evaluate endoscopic remission at Week 64 using the Simple Endoscopic Score for Crohn's Disease (SES-CD). These objectives are clinically relevant as they aim to determine the potential of ozanimod to induce and maintain remission in a population with an inadequate response to conventional therapy, thereby addressing a significant unmet need in pediatric CD management.
Secondary objectives include evaluating the efficacy of ozanimod in achieving clinical remission by PCDAI at Week 12. This assessment provides additional insights into the short-term effectiveness of the treatment, which is crucial for understanding the early therapeutic benefits and optimizing treatment strategies for pediatric patients with active CD.
Participants
The clinical trial involves a total of **70 participants** diagnosed with **moderately to severely active Crohn's Disease**. The study population includes both male and female pediatric subjects, with an age range starting from 2 years old. Participants were selected based on their diagnosis of Crohn's Disease for at least three months prior to the screening visit, confirmed by clinical, endoscopic, and histopathological evidence. The trial includes individuals who have shown an inadequate response, intolerance, or loss of response to previous treatments such as corticosteroids, immunomodulators, or biologic therapies. Participants are required to maintain stable doses of any ongoing background therapies for Crohn's Disease. The trial population is considered vulnerable due to the inclusion of pediatric subjects. Lifestyle considerations such as diet and physical activity are not specified in the available data. The study aims to evaluate the efficacy of ozanimod administered once daily, focusing on achieving clinical remission and endoscopic remission by specific scoring systems at Week 64.
Plans and Procedures
The clinical trial is a **Phase 2/3**, multicenter, randomized, double-blind study designed to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of oral **ozanimod** in pediatric participants with moderately to severely active **Crohn's disease** who have shown an inadequate response to conventional therapy. The trial aims to assess clinical remission by the Pediatric Crohn's Disease Activity Index (PCDAI) and endoscopic remission by the Simple Endoscopic Score for Crohn's Disease (SES-CD) at Week 64. The study is expected to run from June 2022 to October 2024, with participants involved for a duration of up to 64 weeks.
Participants will undergo a series of study visits, beginning with a screening visit to confirm eligibility based on criteria such as a PCDAI score of ≥30 and a SES-CD score of ≥6 (or ≥4 for isolated ileal disease). The screening will also ensure participants have an inadequate response to at least one prior treatment for Crohn's disease. Following successful screening, participants will be randomized to receive either ozanimod or a placebo, administered orally in the form of hard capsules. The trial includes follow-up visits to monitor safety and efficacy, with primary endpoints assessed at Week 64 and secondary endpoints at Week 12.
The inclusion visit will involve obtaining informed consent and verifying the participant's ability to adhere to the study protocol, including the ability to swallow capsules. Follow-up visits will occur at regular intervals to assess the participant's response to treatment and monitor any adverse events. The end-of-study visit will evaluate the overall outcomes and gather final data on the primary and secondary endpoints. Participants may be withdrawn from the study early if they experience significant adverse effects, fail to comply with the study protocol, or if the investigator deems it necessary for their safety.
The trial is structured to ensure rigorous assessment of ozanimod's therapeutic potential in this patient population, with a focus on achieving clinical and endoscopic remission. The study's design, including its randomized and double-blind nature, aims to minimize bias and provide robust data on the efficacy and safety of ozanimod in treating pediatric Crohn's disease.
Treatment
The clinical trial involves the administration of **ozanimod**, a selective immunosuppressive agent, in the form of hard capsules. The experimental medication is marketed under the name Zeposia and is available in three different dosages: 0.23 mg, 0.46 mg, and 0.92 mg. The pharmaceutical form of the medication is a hard capsule, and it is intended for **oral use**. The active substance, ozanimod, is of chemical origin and is provided by Bristol-Myers Squibb Pharma EEIG. The maximum daily dose and total dose amounts are set at 9999 mg, with a maximum treatment period of 9999 days, although specific dosing schedules are determined by the study protocol. Participant compliance with the dosing regimen is monitored throughout the trial.
In addition to the experimental treatment, the study may include non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments, as per the study design. These treatments are used to evaluate the efficacy and safety of ozanimod in pediatric participants with moderately to severely active Crohn's Disease who have shown an inadequate response to conventional therapy. The trial aims to assess clinical remission by the Pediatric Crohn's Disease Activity Index (PCDAI) and endoscopic remission by the Simple Endoscopic Score for Crohn's Disease (SES-CD) at Week 64. The study is conducted in a double-blind manner to ensure unbiased results.
Efficacy
The efficacy of **ozanimod** in pediatric participants with moderately to severely active Crohn's Disease will be assessed through a series of predefined endpoints. The primary efficacy endpoints include the proportion of participants achieving a Pediatric Crohn's Disease Activity Index (PCDAI) score of less than 10 at Week 64, and the proportion of participants achieving a Simple Endoscopic Score for Crohn's Disease (SES-CD) of 2 or less, or a SES-CD of 4 points or less with no subscore greater than 1 point at Week 64. Secondary efficacy endpoints will evaluate the proportion of participants achieving a PCDAI score of less than 10 at Week 12.
These efficacy parameters will be measured at specific timepoints, namely Week 12 and Week 64, using validated scales such as the PCDAI and SES-CD. The collection and analysis of these parameters will be conducted in a double-blind manner to ensure the integrity of the data. The study is designed to provide a comprehensive evaluation of the clinical and endoscopic remission rates in the target population, thereby assessing the therapeutic potential of ozanimod in managing Crohn's Disease.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Signed Written Informed Consent
- Type of Participant and Target Disease Characteristics a) Participant is willing and able to adhere to the study visit schedule and other protocol requirements including is willing and able to swallow a capsule until a sprinkle formulation of ozanimod is available. b) Participant has been diagnosed with CD ≥ 3 months prior to the Screening Visit. The diagnosis should be confirmed by clinical and endoscopic evidence and corroborated by a histopathology report (Note: Local histopathology sample collection and analysis may also be performed during endoscopy at Screening if no prior report is readily available). c) Participant has met each of the following 2 criteria: i) A PCDAI score ≥ 30. ii) Participant has a SES-CD score ≥ 6 (or SES-CD ≥ 4 in participants with isolated ileal disease). d) Participant has an inadequate response, intolerance, or loss of response to at least 1 of the following treatments for CD. i) corticosteroids (eg, oral prednisone, oral budesonide MMX, intravenous [IV] corticosteroids). ii) immunomodulators (eg, AZA, 6-MP, cyclosporine, MTX). iii) biologic therapy (eg, ustekinumab, abatacept, infliximab, etanercept, adalimumab, anakinra, rituximab, vedolizumab). iv) other systemic immunomodulatory therapies for CD. e) If the participant is taking the following background therapies for CD, a stable dose must be maintained as indicated below (dosage regimen can be adjusted to accommodate mg/kg/day dosing as appropriate): i) Oral aminosalicylates (eg, mesalamine, sulfasalazine, olsalazine, balsalazide), the dose must have been stable starting 3 weeks prior to Screening endoscopy. ii) Prednisone (≤ 0.5 mg/kg/day up to 20 mg/day), the dose must have been stable starting 2 weeks prior to Screening endoscopy and must remain stable through the first 5 weeks of treatment. iii) Oral budesonide therapy (doses ≤ 9 mg per day) or oral beclomethasone (doses ≤ 5 mg per day), the dose must have been stable starting 2 weeks prior to Screening endoscopy and must remain stable through the first 5 weeks of treatment. a) Participant must have documentation of vaccinations per standard immunization schedule including complete varicella vaccination at least 30 days prior to randomization (Day 1) ordocumentation of positive varicella zoster virus (VZV) immunoglobulin G (IgG) antibody prior to randomization (Day 1).
- Age of Participant
Exclusion Criteria
- a) Participant has clinically relevant 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 participant at risk by participating in the study. i) Clinically relevant pulmonary conditions include, but are not limited to, history of severe or chronic lung disease, bronchopulmonary dysplasia, cystic fibrosis, or severe asthma (ie, that interferes with normal activities of daily living). b) Participant is likely to require, in the physician’s judgment, bowel resection within 12 weeks of entry into the study. c) Participant has a diagnosis of UC, indeterminate colitis, radiation colitis, or ischemic colitis, or has strictures with prestenotic dilatation, requiring procedural intervention, or with obstructive symptoms. In addition, participants with colonic or ileal strictures that are not passable with an age-appropriate colonoscope that the endoscopist normally uses in clinical practice, or strictures in the ileum or ileocecal valve that are fibrotic in nature, will be excluded. d) Participant has current stoma, ileal-anal pouch anastomosis, fistula that is likely to require, in the physician’s judgment, surgical or medical intervention within 12 weeks of entry into the study or need for ileostomy or colostomy. e) Participant has extensive small bowel resection (> 100 cm) or known diagnosis of short bowel syndrome or participant requires total parenteral nutrition. f) Participant has suspected or diagnosed intra-abdominal or perianal abscess that has not been appropriately treated. g) Participant has documentation of positive test for toxigenic Clostridioides difficile (formerly Clostridium difficile [C difficile]) by polymerase chain reaction examination of the stool during Screening. If positive, participants may be rescreened after appropriate treatment and negative retest no earlier than 7 days after completion of treatment. h) Participant has documentation of positive examination for pathogens (ova, parasites, and bacteria). If positive, participants may be treated and rescreened.i) Participant requires or is expected to undergo apheresis (eg, Adacolumn apheresis) within 2 weeks of randomization (Day 1). j) Participant is pregnant, lactating, has a positive serum β-subunit human chorionic gonadotropin (β-hCG) measured during Screening or a positive urine pregnancy test on Day 1. k) Participant has a history or presence of the following clinically relevant cardiovascular conditions: i) Structural cardiac disease (eg, hypertrophic obstructive cardiomyopathy, unrepaired congenital heart defects). Participants with repaired congenital heart defects should be discussed with the Clinical Trial Physician or designee prior to enrollment. ii) Cardiac events (eg, myocardial infarction) or diseases that predispose to cardiac complications. iii) History of stroke, heart failure, or symptomatic bradycardia defined as < 5th percentile of normal sinus rhythm HR for age 29 [...]
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Not Recruiting | 30 Jun 2022 | 12 |
 France | Not Recruiting | 30 Jun 2022 | 8 |
 Germany | Not Recruiting | 30 Jun 2022 | 4 |
 Hungary | Not Recruiting | 30 Jun 2022 | 4 |
 Poland | Not Recruiting | 30 Jun 2022 | 12 |
 Spain | Not Recruiting | 30 Jun 2022 | 10 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Zeposia 0.23 mg hard capsules
Zeposia 0.46 mg hard capsules | Test | HARD CAPSULES | ORAL USE | 9999 | 9999 | PRD9257549 |
Zeposia 0.23 mg hard capsules
Zeposia 0.46 mg hard capsules | Test | HARD CAPSULES | ORAL USE | 9999 | 9999 | PRD9257566 |
Zeposia 0.92 mg hard capsules | Test | HARD CAPSULES | ORAL USE | 9999 | 9999 | PRD9257552 |