A phase 2/3, multicenter, randomized, double-blind study to evaluate the efficacy, safety, pharmacokinetics and pharmacodynamics of oral ozanimod (RPC1063) in pediatric subjects with moderately to severely active ulcerative colitis with an inadequate response to conventional therapy.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Bristol-Myers Squibb Services Unlimited Company

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

11 Mar 2022 → ongoing

Decision date (initial)

2024-03-27

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2023-509248-86-00

EudraCT number

2021-002308-11

WHO UTN

U1111-1268-2191

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Pharmacogenomic, Therapy, Pharmacodynamic, Dose response, Safety

To evaluate the efficacy of ozanimod in pediatric subjects with moderately to severely active UC (3-component Mayo Score: clinical remission, Week 52)

Secondary objectives 10

1. Evaluate the efficacy of ozanimod in pediatric subjects with moderately to severely active UC (3-component Mayo Score: clinical remission, Week 10)
2. Evaluate the efficacy of ozanimod in pediatric subjects with moderately to severely active UC (3-component Mayo Score: clinical response, Week 52)
3. Evaluate the efficacy of ozanimod in pediatric subjects with moderately to severely active UC (3-component Mayo Score: clinical response, Week 10)
4. Evaluate symptomatic remission
5. Evaluate time to achieve symptomatic remission
6. Evaluate endoscopic improvement by Mayo Endoscopy Score
7. Evaluate corticosteroid-free remission
8. Evaluate the safety and tolerability of 2 doses of ozanimod in pediatric subjects w/moderately-severely active UC
9. Characterize the pharmacokinetics of 2 doses of ozanimod and its major active metabolites in pediatric subjects with moderately-severely active UC
10. Evaluate the pharmacodynamic effects of 2doses of ozanimod in pediatric subjects w/moderately-severely active UC

Conditions and MedDRA coding

Moderately to Severely Active Ulcerative Colitis

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-001710-PIP03-17

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. Moderately to severely active Ulcerative Colitis (UC) diagnosed prior to the Screening Visit
2. Evidence of UC extending beyond the rectum, as determined by baseline endoscopy
3. Has had an inadequate response, loss of response to, or is intolerant to at least 1 of the following treatments for UC: oral aminosalicylates, systemic corticosteroids, immunomodulators, biologic therapy

Exclusion criteria 4

1. Diagnosis of Crohn's disease or indeterminate colitis
2. Has documentation of positive test for toxin producing Clostridium difficile, or polymerase chain reaction examination of the stool
3. Apheresis within 2 weeks of randomization
4. History of or currently active primary or secondary immunodeficiency, or participants with known genetic disorders as a cause for colitis

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. 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
2. Proportion of subjects who achieve histological remission, defined as the following: - Geboes index score < 2.0 - Robarts Histopathology Index (RHI) ≤ 3, with subscores of 0 for both lamina propria neutrophils and neutrophils in the epithelium
3. Early Discontinuation: Starting at Week 5 or later if either one of the following criteria are met at 2 consecutive visits that are at least 2 weeks apart: - Partial Mayo score is ≥ 7 and is the same or worse than baseline, AND rectal bleeding and stool frequency are not improved from baseline - Partial Mayo score is 6 and worse than baseline, AND rectal bleeding and stool frequency are not improved from baseline

Secondary endpoints 8

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

Investigational products

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

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Bristol-Myers Squibb Services Unlimited Company

Sponsor organisation

Bristol-Myers Squibb Services Unlimited Company

Address

Plaza 254, Blanchardstown Corporate Park 2 Blanchardstown Corporate Park 2

City

Dublin 15

Postcode

D15 T867

Country

Ireland

Scientific contact point

Organisation

Bristol-Myers Squibb Services Unlimited Company

Contact name

GSM-CT

Public contact point

Organisation

Bristol-Myers Squibb Services Unlimited Company

Contact name

GSM-CT

Third parties 13

Locations

5 EU/EEA countries · 20 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

Documents 72 files

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

Application history

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