Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Oral Ozanimod in Pediatric Participants with Moderately to Severely Active Crohn's Disease with an Inadequate Response to Conventional Therapy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Celgene International II S.a.r.l.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

16 May 2023 → 14 Sep 2024

Decision date (initial)

2024-02-05

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Celgene Corporation, USA

External identifiers

EU CT number

2023-508777-91-00

EudraCT number

2021-005019-30

WHO UTN

U1111-1275-2700

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety, Pharmacodynamic, Pharmacokinetic

To evaluate the efficacy of ozanimod once daily in pediatric participants with moderately to severely active CD: clinical remission by PCDAI at Week 64
To evaluate endoscopic remission at Week 64 by SES-CD

Secondary objectives 1

1. To evaluate the efficacy of ozanimod once daily in pediatric participants with moderately to severely active CD: clinical remission by PCDAI at Week 12

Conditions and MedDRA coding

Moderately to Severely Active Crohn's Disease

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-001710-PIP04-17

Plan to share IPD

Yes

IPD plan description

BMS will provide access to individual anonymized participant data upon request from qualified researchers, and subject to certain criteria. Additional information regarding Bristol Myers Squibb's data sharing policy and process can be found at: https://www.bms.com/researchers-and-partners/clinical-trials-and-research/disclosure-commitment.html.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Signed Written Informed Consent
2. 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).
3. Age of Participant

Exclusion criteria 1

1. 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 [...]

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of participants who achieve PCDAI < 10 at Week 64 Proportion of participants achieving SES-CD ≤ 2 or SES-CD ≤ 4 points with no SES-CD subscore > 1 point at Week 64

Secondary endpoints 1

1. Proportion of participants who achieve PCDAI < 10 at Week 12

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Celgene International II S.a.r.l.

Sponsor organisation

Celgene International II S.a.r.l.

Address

Route De Perreux 1

City

Boudry

Postcode

2017

Country

Switzerland

Scientific contact point

Organisation

Celgene International II S.a.r.l.

Contact name

GSM-CT

Public contact point

Organisation

Celgene International II S.a.r.l.

Contact name

GSM-CT

Third parties 6

Locations

6 EU/EEA countries · 25 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 58 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications