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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Celgene International II SARL

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

5 Oct 2018 → 1 Nov 2024

Decision date (initial)

2024-05-16

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-511553-22-00

EudraCT number

2017-004295-55

WHO UTN

U1111-1203-8203

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Pharmacodynamic, Therapy, Efficacy

The objective of this study is to demonstrate the long-term safety and explore long-term efficacy of ozanimod for the treatment of subjects with moderately to severely active CD.

Secondary objectives 1

1. Not applicable

Conditions and MedDRA coding

Moderately to Severely Active Crohn's Disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Subjects who are not in clinical response and/or clinical remission after completing 12 weeks in the Induction Studies RPC01-3201 or RPC01-3202, subjects who experience relapse in the Maintenance Study RPC01-3203, subjects who complete the Maintenance Study RPC01- 3203, subjects who complete at least 1 year of RPC01 2201.
2. 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.
3. Female subjects of childbearing potential (FCBP): Note: For the purposes of this study, a female subject is considered to be of childbearing potential if she 1) has not undergone a hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of both ovaries) or 2) has not been postmenopausal for at least 24 consecutive months (that is, has had menses at any time during the preceding 24 consecutive months). Must agree to practice a highly effective method of contraception 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. Examples of acceptable methods of birth control in the study are the following: • combined hormonal (containing oestrogen and progestogen) contraception, which may be oral, intravaginal, or transdermal • progestogen-only hormonal contraception associated with inhibition of ovulation, which may be oral, injectable, or implantable • placement of an intrauterine device (IUD) • placement of an intrauterine hormone-releasing system (IUS) • bilateral tubal occlusion • vasectomized partner • complete sexual abstinence. Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhoea method are not acceptable methods of contraception. Female condom and male condom should not be used together. Counseling about pregnancy precautions and the potential risks of fetal exposure must be conducted for FCBP. The Investigator will educate all FCBP about the different options of contraceptive methods or abstinence at Day 1, as appropriate. The subject will be re-educated every time her contraceptive measures/methods or ability to become pregnant changes. The female subject's chosen form of contraception must be effective by the time the female subject starts the study (for example, hormonal contraception should be initiated at least 28 days before Day 1).

Exclusion criteria 9

1. 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
2. Subject is pregnant, lactating, or has a positive urine beta human chorionic gonadotropin (β-hCG) test
3. Subject has suspected or diagnosed intra-abdominal or perianal abscess that has not been appropriately treated
4. Hypersensitivity to active ingredients or excipients of ozanimod
5. Subject has received any of the following therapies since the first dose of IP in the prior ozanimod study: • treatment with a biologic agent as well as other treatments for CD such as etrasimod, filgotinib, upadacitinib • treatment with an investigational agent other than ozanimod • treatment with D-penicillamine, leflunomide, thalidomide, natalizumab, fingolimod or other S1P modulators • treatment with lymphocyte-depleting therapies (eg, Campath®, anti- CD4, cladribine, rituximab, ocrelizumab, cyclophosphamide, mitoxantrone, total body irradiation, bone marrow transplantation, alemtuzumab, daclizumab)
6. Subject is currently receiving or requires initiation of any of the following therapies: • treatment with corticosteroids at a dose that exceeds the prednisone equivalent of >40 mg • treatment with immunomodulatory agents (eg, AZA, 6-MP, or MTX) • chronic non-steroidal 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) • treatment with Class Ia or Class III anti-arrhythmic drugs or treatment with 2 or more agents in combination known to prolong PR interval, or treatment with additional prohibited systemic cardiac medication • treatment with breast cancer resistance protein (BCRP) inhibitors (eg, cyclosporine, eltrombopag)
7. Subject is receiving treatment with any of the following drugs or interventions: • CYP2C8 inducers (eg, rifampicin) • Monoamine oxidase inhibitors (eg, selegiline, phenelzine)
8. Subject has any clinically significant abnormal results (eg, labs or ECG) which in the opinion of the Investigator may put the subject at risk.
9. Subjects has a pre-dose resting HR < 55 bpm. One recheck is allowed at the Day 1 visit. If HR remains < 55 bpm at Day 1, one additional recheck is allowed at a later date within the available window for rollover from the previous study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 17

1. Proportion of subjects with a CDAI score of < 150
2. Proportion of subjects with a SES-CD decrease from baseline of ≥ 50%
3. Proportion of subjects with average daily abdominal pain score ≤ 1 point, and average daily stool frequency ≤ 3 points with abdominal pain and stool frequency no worse than baseline
4. Proportion of subjects with CDAI reduction from baseline of ≥ 100 points or CDAI score of < 150
5. Proportion of subjects with absence of ulcers ≥ 0.5 cm with no segment with any ulcerated surface ≥ 10%
6. Proportion of subjects with CDAI reduction from baseline of ≥ 70 points
7. Change from baseline in CDAI
8. Proportion of subjects with CDAI reduction from baseline of ≥ 100 points or CDAI score of < 150 and SES-CD decrease from baseline of ≥ 50%
9. Proportion of subjects with CDAI score of < 150 and SES-CD ≤ 4 points and a SES CD decrease ≥ 2 points
10. Proportion of subjects with average daily abdominal pain score ≤ 1 point and average daily stool frequency ≤ 3 points and a stool frequency no worse than baseline and SES-CD ≤ 4 points and a SES-CD decrease ≥ 2 points
11. Proportion of subjects with SES-CD ≤ 4 points and a SES-CD decrease ≥ 2 points
12. Proportion of subjects with a CDAI score < 150 in subjects off corticosteroids
13. Proportion of subjects with a Crohn's Disease Endoscopic Index of Severity (CDEIS) decrease from baseline of ≥ 50%
14. Proportion of subjects with average daily abdominal pain score ≤ 1 point, average daily stool frequency ≤ 3 points with abdominal pain and stool frequency no worse than baseline, and SES-CD decrease from baseline ≥ 50%
15. Efficacy in subjects (clinical response, clinical remission, and endoscopic improvement) as a function of baseline and change- from baseline in biomarkers (eg, C-reactive protein, fecal calprotectin, high-density lipoprotein, IgA, IL-7)
16. To assess impact of SARS-CoV-2 serologic status on subjects receiving ozanimod and CD
17. Exploratory measurements of SARS-CoV-2 serology (anti-SARS-CoV-2 total or IgG), from serum samples collected every 48 weeks.

Secondary endpoints 1

1. Not applicable

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Celgene International II SARL

Sponsor organisation

Celgene International II SARL

Address

Route De Perreux 1

City

Boudry

Postcode

2017

Country

Switzerland

Scientific contact point

Organisation

Celgene International II SARL

Contact name

GSM-CT

Public contact point

Organisation

Celgene International II SARL

Contact name

GSM-CT

Third parties 8

Locations

15 EU/EEA countries · 73 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 77 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