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

• Register: EUCTR
• Last refreshed on: 10 February 2025
• Main ID: EUCTR2017-004293-33-SE
• Date of registration: 08/03/2018
• Prospective Registration: Yes
• Primary sponsor: Celgene International II Sàrl
• Public title: Multicenter Study of Oral Ozanimod as Induction Therapy in patients with Moderately to Severely Active Crohn’s Disease
• Scientific title: Induction Study #2 - A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of Oral Ozanimod as Induction Therapy for Moderately to Severely Active Crohn’s Disease
• Date of first enrolment: 23/05/2018
• Target sample size: 675
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-004293-33
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Austria, Bulgaria, Canada, China, Finland, France, Georgia, Germany, Greece, Hong Kong, Hungary, Israel, Korea, Republic of, Lithuania, Mexico, Netherlands, Poland, Portugal, Russian Federation, Saudi Arabia, Serbia, Singapore, Slovakia, Slovenia, South Africa, Spain, Sweden, Turkey, Ukraine, United States

Contacts

• Name: Keith Usiskin
• Affiliation: Celgene International II Sàrl

• Name: Keith Usiskin
• Affiliation: Celgene International II Sàrl

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male or female subjects aged 12 to 75 years (at Screening), inclusive with adolescents (12 to 17) with a body weight = 45 kg
2. Note: Countries or sites with local restrictions that prohibit enrollment of adolescents (aged 12 to 17 years) will only enroll subjects who are 18 years of age or older. Enrollment of adolescent subjects will begin only after the applicable regulatory requirements for enrolling subjects in that age group have been satisfied and the necessary health authority agreements have been granted. Where national or regional guidelines for the definition of adolescence differ from the definition stated above, the national or regional guidelines may be used to determine eligibility.
Subjects should not have any constraints under local regulations and must provide written informed consent prior to any study-related procedures, and have the ability to comply with the Table of Events. For adolescents, a parent/legal guardian of the adolescent must sign the informed consent form. In addition, adolescent subjects must also agree to participate in the study by signing an assent form. A parent or guardian must be willing to supervise adherence to the protocol requirements. Adolescent subjects who reach the legal age of consent while participating in the study will be asked to sign an ICF themselves to acknowledge their willingness to continue in the study
3. Subject has signs and symptoms consistent with a diagnosis of CD for at least 3 months (prior to first IP administration). The diagnosis should be confirmed by clinical and endoscopic evidence and corroborated by a histology report. (Note: endoscopy and histopathology confirmation may be obtained during Screening if no prior report is readily available).
4. Subject has met each of the following 2 criteria:
? a CDAI score = 220 and = 450
? an average daily stool frequency = 4 points and/or an abdominal pain of = 2 points
5. Subject has a SES-CD score of = 6 (or SES-CD = 4 in subjects with isolated ileal disease).
6. Subject has an inadequate response or loss of response to or is intolerant of at least 1 of
the following CD treatments: corticosteroids, immunomodulators, biologic therapy (eg, ustekinumab, TNFa antagonists, or vedolizumab)
7. If the subject is taking the following background therapies for CD, a
stable dose must be maintained as indicated below:
? oral aminosalicylates (eg, mesalamine, sulfasalazine, olsalazine, balsalazide) with a stable dose for at least 3 weeks prior to Screening endoscopy
? prednisone (doses = 20 mg per day) or equivalent with a stable dose for at least 2 weeks prior to Screening endoscopy
? budesonide therapy (doses = 9 mg per day) or beclomethasone doses = 5 mg/day at a stable dose for at least 2 weeks prior to the Screening endoscopy
8. Subject at high risk (ie, family history, CD duration) for colonic malignancy has documented evidence of having had a surveillance colonoscopy within the last 2 years or according to local and national medical guidelines to evaluate for polyps, dysplasia, or malignancy. If there is no recent history of surveillance colonoscopy, this can be done as part of the colonoscopy performed during Screening. Any visualized adenomatous polyps must be removed and any suspicious lesion confirmed free of cancer and/or dysplasia prior to randomization.
9. Female subjects of childbearing potential (FCPB):
Note: For the purposes of this study, a female patient is considered to be of childbearing poten
Exclusion criteria:
1. Subject has any clinically relevant 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 subject at risk by participating in the study. 2. Subject is likely to require, in the physician's judgment, bowel resection within 12 weeks of entry into the study. 3. Subject has a diagnosis of UC, indeterminate colitis, radiation colitis, or ischemic colitis, or has strictures with prestenotic dilatation 4. Subject has current stoma, ileal-anal pouch anastomosis, fistula that is likely to require, surgical or medical intervention within 12 weeks of entry into the study or need for ileostomy or colostomy. 5. Subject has extensive small bowel resection (> 100 cm) or known diagnosis of short bowel syndrome, or subject requires total parenteral nutrition. 6. Subject has suspected or diagnosed intra-abdominal or perianal abscess that has not been appropriately treated. 7. Subject has documentation of positive test for toxin producing C. difficile, or PCR examination of the stool. 8. Subject has documentation of positive examination for pathogens 9. Subject is pregnant, lactating, or has a positive serum ß-hCG measured during Screening. 10. Subject has any condition that would make implementation of the protocol or interpretation of the study difficult. 11. Subject has a history of diabetes mellitus type 1, or uncontrolled diabetes mellitus type 2 with hemoglobin A1c (HbA1c) > 9%, or is a diabetic subject with significant comorbid conditions such as retinopathy or nephropathy. 12. Subject has a history of uveitis or clinically confirmed diagnosis of macular edema. 13. Subject has a known active bacterial, viral, fungal, mycobacterial infection (including tuberculosis or atypical mycobacterial disease) or any major episode of infection that required hospitalization or treatment with IV antibiotics within 30 days of Screening or oral antibiotics within 14 days of Screening. 14. History or known presence of recurrent or chronic infection (eg, hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV); recurrent urinary tract infections are allowed. 15. Subject has a history of cancer within 5 years, including solid tumors and hematological malignancies or colonic dysplasia that has not been completely removed 16. Subject has a history of alcohol or drug abuse within 1 year prior to initiation of Screening 17. Hypersensitivity to active ingredients or excipients of ozanimod or placebo. 18. Prior participation in an ozanimod clinical study 19. Subject has a history of primary nonresponse to 2 or more approved biologic agents or has been treated with 4 or more biologics for CD 20. Subject has been treated with a biologic agent within 8 weeks or 5 elimination half-lives (whichever is shorter) prior to the first dose of IP 21. Subject has a history of treatment with an investigational agent within 5 elimination half-lives of that agent prior to the first dose of IP 22. Subject has received a live or live attenuated vaccine within 4 weeks prior to the first dose of IP 23. Subject has received previous treatment with lymphocyte-depleting therapies 24. Subject has received previous treatment with D-penicillamine, leflunomide, orthalidomide 25. Subject has received previous treatment with natalizumab or fingolimod or other S1P receptor modulators 26. Subject has received previou

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Moderately to Severely Active Crohn’s Disease
MedDRA version: 20.0 Level: PT Classification code 10011401 Term: Crohn's disease System Organ Class: 10017947 - Gastrointestinal disorders

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Intervention(s)

Product Name: ozanimod
Product Code: RPC1063 (equivalent to ozanimod HCl)
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Ozanimod
Other descriptive name: OZANIMOD
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.25-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Product Name: ozanimod
Product Code: RPC1063 (equivalent to ozanimod HCl)
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Ozanimod
Other descriptive name: OZANIMOD
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): Proportion of subjects with a CDAI score < 150 at Week 12

Main Objective: Demonstrate the efficacy of ozanimod compared to placebo on the induction of clinical remission

Timepoint(s) of evaluation of this end point: Subjects will be deemed a responder with respect to this endpoint if they meet the definition for CDAI Clinical Remission at Week 12.

Secondary Objective: - Demonstrate the efficacy of ozanimod compared to placebo on induction of clinical response, endoscopic response, endoscopic remission, and histologic improvement
- Evaluate the efficacy of ozanimod compared to placebo, in subjects who had previously received biologic therapy (eg, anti-IL-12, anti-IL-23, anti-TNF, or anti-integrin therapy)
- Demonstrate the efficacy of ozanimod compared to placebo on the induction of clinical remission and clinical response in adolescent subjects (aged 12 to 17 years, inclusive)
- Characterize the population pharmacokinetics (PK) and PK/pharmacodynamics (PD) relationship of ozanimod
- Demonstrate the safety and tolerability of ozanimod as induction therapy

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: at Week 12

Secondary end point(s): Major Secondary Endpoints:
- 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 at Week 12
- Proportion of subjects with a Simple Endoscopic Score for Crohn’s Disease (SES-CD) score decrease from baseline of = 50% at Week 12
- Proportion of subjects with CDAI reduction from baseline of = 100 points or CDAI score < 150 at Week 12
- 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 12

Secondary ID(s)

2017-004293-33-HU

NCT03440385

RPC01-3202

Source(s) of Monetary Support

Celgene International II Sàrl

Ethics review

Status: Approved
Approval date: 23/05/2018
Contact:

Results

• Results available: Yes
• Date Posted: 27/11/2024
• Date Completed: 21/11/2023
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2017-004293-33/results