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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Celgene International II S.a.r.l.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

27 Sep 2018 → 3 Oct 2024

Decision date (initial)

2024-03-27

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Celgene Corporation United States

External identifiers

EU CT number

2023-510426-33-00

EudraCT number

2017-004294-14

WHO UTN

U1111-1203-8002

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Pharmacogenetic, Pharmacokinetic, Safety, Pharmacodynamic, Efficacy

Demonstrate the efficacy of ozanimod compared to placebo on the maintenance of clinical remission and endoscopic response

Secondary objectives 5

1. Demonstrate the efficacy of ozanimod compared to placebo on maintenance of clinical response
2. Demonstrate the efficacy of ozanimod compared to placebo on maintenance of endoscopic remission and mucosal healing
3. Demonstrate the efficacy of ozanimod, compared to placebo, in achieving corticosteroid-free remission
4. Demonstrate the efficacy of ozanimod, compared to placebo, on healthcare resource utilization (HRU), subject-reported outcomes, and quality of life
5. Demonstrate the safety and tolerability of ozanimod as maintenance therapy

Conditions and MedDRA coding

Moderately to Severely Active Crohn's Disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Subject fulfilled the inclusion criteria at time of entry into the Induction Study (RPC01 3201 or RPC01-3202) and has completed the Week 12 efficacy assessments of the Induction Study.
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. Subject is in clinical response (a reduction from baseline in CDAI of ≥ 100 points or CDAI score of < 150 points) and/or clinical remission (CDAI score of < 150 points) and/or has an average daily stool frequency score ≤ 3 and an average abdominal pain score ≤ 1 with abdominal pain and stool frequency no worse than baseline at Week 12 of the Induction Study.
4. Female subjects of childbearing potential (FCBP) must agree to practice a highly effective method of contraception throughout the study until completion of the 90-day Safety Follow-up Visit. Examples of acceptable methods of birth control in the study are the following: a) combined hormonal (containing oestrogen and progestogen) contraception, which may be oral, intravaginal, or transdermal b) progestogen-only hormonal contraception associated with inhibition of ovulation, which may be oral, injectable, or implantable c) placement of an intrauterine device (IUD) d) placement of an intrauterine hormone-releasing system (IUS) e) bilateral tubal occlusion f) vasectomized partner g) complete sexual abstinence

Exclusion criteria 20

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 has received treatment with Class Ia or Class III antiarrhythmic drugs, treatment with 2 or more agents in combination known to prolong PR interval or treatment with additional prohibited systemic cardiac medication provided in Table 7.
3. Subject has received a live or live attenuated vaccine within 4 weeks prior to first dose of IP in this study.
4. Subject is pregnant, lactating, or has a positive urine beta human chorionic gonadotropin (β-hCG) test measured prior to randomization.
5. Subject has suspected or diagnosed intra-abdominal or perianal abscess that has not been appropriately treated.
6. Subject has undergone a colectomy (partial or total), small bowel resection, or an ostomy (ie, temporary colostomy, permanent colostomy, ileostomy, or other enterostomy) since Day 1 of the Induction Studies or has developed symptomatic fistula (enterocutaneous or entero enteral).
7. Subject has had cancer within 5 years including solid tumors and hematological malignancies (except basal cell and in situ squamous cell carcinomas of the skin or cervical dysplasia/cancer that have been excised and resolved); or colonic dysplasia that has not been completely removed.
8. Hypersensitivity to active ingredients or excipients of ozanimod or placebo
9. Subject has received any of the following therapies during the Induction Study: a. rectal steroid therapy (ie, steroids administered to the rectum or sigmoid via foam or enema) b. post-baseline (of induction) initiation of, or increase in, corticosteroids to treat worsening CD to a dose greater than the maximum daily dose taken between the screening and baseline visits c. rectal 5- aminosalicylates (ASA) (ie, 5-ASA administered to the rectum) d. parenteral corticosteroids > 14 days e. total parenteral nutrition therapy f. antibiotics for the treatment of CD g. immunomodulatory agents (6-MP, AZA, including but not limited to cyclosporine, mycophenolate mofetil, tacrolimus, and sirolimus) h. immunomodulatory biologic agents as well as other treatments for CD such as etrasimod, filgotinib, and upadacitinib i. investigational agents j. apheresis
10. Subject has current or planned treatment with immunomodulatory agents (eg, AZA, 6-MP, or MTX) during the Maintenance Study.
11. Subject has chronic nonsteroidal 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).
12. Subject has received previous treatment with lymphocyte-depleting therapies (eg, Campath™, anti-CD4, cladribine, rituximab, ocrelizumab, cyclophosphamide, mitoxantrone, total body irradiation, bone marrow transplantation, alemtuzumab, or daclizumab).
13. Subject has received previous treatment with D-penicillamine, leflunomide or thalidomide within 8 weeks of first dose of IP in Induction.
14. Subject has received previous treatment with natalizumab, fingolimod, or other S1P modulators.
15. Subject has received previous treatment with cyclosporine, tacrolimus, sirolimus, or mycophenolate mofetil within 16 weeks of initiation of Induction Screening.
16. Subject has a history of treatment with intravenous immunoglobulin (IVIg) or plasmapheresis, within 3 months prior to first dose of IP in Induction.
17. Subject is receiving treatment with breast cancer resistance protein (BCRP) inhibitors (eg, cyclosporine, eltrombopag)
18. Subject is receiving treatment with any of the following drugs or interventions a. CYP2C8 inducers (eg, rifampicin) b. Monoamine oxidase inhibitors (eg, selegiline, phenelzine)
19. Subjects who have met the discontinuation criteria in the Induction Period
20. Subject has any clinically significant abnormal results (eg, labs or ECG) which, in the opinion of the investigator, may put the subject at risk.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Proportion of subjects with a CDAI score of < 150 at Week 52
2. Proportion of subjects with a Simple Endoscopic Score for Crohn's Disease (SES-CD) decrease from baseline of ≥ 50% at Week 52

Secondary endpoints 16

1. Proportion of subjects with CDAI reduction from baseline of ≥ 100 points or CDAI score of < 150 at Week 52
2. 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 at Week 52
3. Proportion of subjects with a CDAI score < 150 at Week 52, while remaining corticosteroid free in the prior 12 weeks
4. Proportion of subjects with a CDAI score of < 150 at Week 52 in subjects with a CDAI score < 150 at pre-randomization
5. Proportion of subjects with a CDAI score of < 150 at Week 52 and at ≥ 80% of visits between Week 8 and Week 52, inclusive, in subjects with a CDAI score < 150 at pre randomization
6. Proportion of subjects with absence of ulcers ≥ 0.5 cm with no segment with any ulcerated surface ≥ 10% at Week 52
7. Histologic improvement based on differences between ozanimod and placebo in histologic disease activity scores (ie, Global Histologic Disease Activity Score [GHAS] changes (Geboes, 2000)) at Week 52
8. Proportion of subjects with average daily abdominal pain score ≤ 1 point, and average daily stool frequency score ≤ 3 points with abdominal pain and stool frequency no worse than baseline and an SES-CD decrease from baseline of ≥ 50% at Week 52
9. Proportion of subjects with CDAI score of < 150 and SES-CD decrease from baseline of ≥ 50% at Week 52
10. Proportion of subjects with average daily abdominal pain score ≤ 1 point, and average daily stool frequency scor≤ 3 points with abdominal pain and stool frequency no worse than baseline and an SES-CD ≤ 4 points and a SES-Ce D decrease ≥ 2 points at Week 52
11. Proportion of subjects with CDAI reduction from baseline of ≥ 100 points or CDAI score < 150 and SES-CD decrease from baseline of ≥ 50% at Week 52
12. Proportion of subjects with CDAI score < 150 at Week 12 and SES-CD decrease from baseline of ≥ 50% at Week 52
13. Proportion of subjects with CDAI reduction from baseline of ≥ 70 points at Week 52
14. Proportion of subjects with mucosal healing (SES-CD ≤ 4 points and a SES-CD decrease ≥ 2 points) and histologic improvement by GHAS or Robarts Histologic Index (RHI) at Week 52
15. Time to relapse (an increase in the CDAI score from Maintenance Day 1 of ≥ 100 points and a CDAI score > 220, SES-CD score ≥ 6 [or ≥ 4 if isolated ileal disease]), and exclusion of other causes of an increase in disease activity unrelated to underlying CD (eg, infections, change in medication)
16. Proportion of subjects with a Crohn's Disease Endoscopic Index of Severity (CDEIS) decrease from baseline of ≥ 50% at Week 52

Investigational products

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

Test 2

Placebo 1

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 8

Locations

14 EU/EEA countries · 75 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 54 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