Multicenter Study of Oral Ozanimod as Induction Therapy in patients with Moderately to Severely Active Crohn’s Disease
- Conditions
- Therapeutic area: Diseases [C] - Digestive System Diseases [C06]Moderately to Severely Active Crohn’s DiseaseMedDRA version: 20.0Level: PTClassification code 10011401Term: Crohn's diseaseSystem Organ Class: 10017947 - Gastrointestinal disorders
- Registration Number
- EUCTR2017-004293-33-ES
- Lead Sponsor
- Celgene International II Sàrl
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 600
1. Male or female subjects aged 18 to 75 years (at Screening), inclusive.
2. Subject must provide written informed consent prior to any study-related procedures, and
have the ability to comply with the Table of Events.
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, he/she must be on a stable dose 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:
Must agree to practice a highly effective method of contraception throughout the study until completion of the 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. 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
- Vasectomised partner
- Sexual abstinence
Male subjects:
Must agree to use a latex condom during sexual contact with women of childbearing potential while participating in the study until completion of the safety follow-up visit.
All subjects:
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.
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 known strictures or stenosis leading to symptoms of obstruction.
4. Subject has current stoma, ileal-anal pouch anastomosis, symptomatic fistula, 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 a positive test for toxin producing C. difficile, or PCR examination of the stool on their most recent test, which must have been done in the past 60 days.
8. Subject has documentation of positive examination for pathogens (ova and parasites, and bacteria), which must have been done in the past 60 days.
9. Subject is pregnant, lactating, or has a positive serum beta human chorionic gonadotropin (ß-hCG) measured during Screening.
10. Subject has clinically relevant cardiovascular conditions, making implementation of the protocol or interpretation of the study difficult or that would put the subject at risk by participating in the study
11. Subject has a history of diabetes mellitus type 1, or uncontrolled diabetes mellitus type 2 with HbA1c > 9%, or is a diabetic subject with significant comorbid conditions such as retinopathy or nephropathy.
12. Subject has a history of uveitis (within last year) or clinically confirmed diagnosis of macular edema
13. Subject has a known active bacterial, viral, fungal, mycobacterial infection, or other infection 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, virus HBV, HCV or HIV); recurrent urinary tract infections are allowed
15. Subject has a history of active 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. Subject has a history of primary nonresponse to 2 or more approved biologic therapies used for the treatment of CD
18. Subject has been treated with a biologic agent within 8 weeks or 5 elimination half-lives prior to the first dose of IP
19. 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 20. Subject has received a live vaccine within 4 weeks prior to the first dose of IP
21. Subject has received previous treatment with lymphocyte-depleting therapies
22. Subject has received previous treatment with D-penicillamine, leflunomide, or thalidomide
23. Subject has received previous treatment with natalizumab or fingolimod
24. Subject has received previous treatment with cyclosporine, tacrolimus, sirolimus, or mycophenolate mofetil within 16
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Demonstrate the efficacy of ozanimod compared to placebo on the induction of clinical remission;Secondary Objective: - Demonstrate the efficacy of ozanimod compared to placebo on induction of clinical response, clinical remission, endoscopic response, endoscopic remission, and histologic improvement<br>- Demonstrate 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)<br>- Characterize the population pharmacokinetics (PK) and PK/pharmacodynamics (PD) relationship of ozanimod<br>- Demonstrate the safety and tolerability of ozanimod as induction therapy;Primary end point(s): Proportion of subjects with a CDAI score < 150 at Week 12;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 Outcome Measures
Name Time Method Secondary end point(s): Major Secondary Endpoints:<br>- Proportion of subjects with average daily abdominal pain score =< 1 point, and average daily stool frequency score =< 3 points and a stool frequency score no worse than baseline at Week 12<br> - Proportion of subjects with a Simple Endoscopic Score for Crohn’s Disease (SES CD) score decrease from baseline of >= 50% at Week 12<br>- Proportion of subjects with CDAI reduction from baseline of >= 100 points or CDAI score < 150 at Week 12<br>- 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;Timepoint(s) of evaluation of this end point: at Week 12