| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Moderately to Severely Active Crohn’s Disease |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10011401 |
| E.1.2 | Term | Crohn's disease |
| E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| Demonstrate the efficacy of ozanimod compared to placebo on the induction of clinical remission |
|
| E.2.2 | Secondary objectives of the trial |
- 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)
- Characterize the population pharmacokinetics (PK) and PK/pharmacodynamics (PD) relationship of ozanimod
- Demonstrate the safety and tolerability of ozanimod as induction therapy |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
| A twenty-four (24)-hour ambulatory blood pressure monitoring substudy will be conducted on a total of approximately 75 adult subjects (~50 active and ~25 placebo subjects) at selected sites, with assessments at 24 hours pre-baseline (ie, between Screening and before Day 1) and 24 hours post-dose on Day 8. At these participating sites, monitoring will be hourly during the day and every two hours at night. Heart rate will also be assessed throughout the 24 hour period at both time points (ie, prebaseline and day 8). Paper diary will be used to collect information on all subjects during the 24 hour period for symptoms associated with changes in blood pressure. |
|
| E.3 | Principal inclusion criteria |
1. Male or female subjects aged 18 to 75 years (at Screening).
2. 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.
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 systemic CD treatments: corticosteroids, immunomodulators, biologic therapies (eg, ustekinumab, TNFα antagonists, or vedolizumab)
7. If the subject is taking the following background therapies for CD, a stable dose must be maintained throughout the study beginning from the screening period 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/per 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 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. Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhoea method are not acceptable methods of contraception.
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 Screening and Day 1, as appropriate. The FCBP's chosen form of contraception must be effective by the time she is randomized into the study.
10. Subject must have documentation of positive varicella zoster virus (VZV) immunoglobulin G (IgG) antibody status or complete VZV vaccination at least 30 days prior to randomization. |
|
| E.4 | Principal exclusion criteria |
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 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. Any other modality used in addition to the colonoscopy to assess this criterion must be discussed with the Medical Monitor. 4. Subject has current stoma, ilealanal 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 β-hCG test 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 macular edema. 13. Subject has a known active bacterial, viral, fungal (excluding fungal infection of nail beds, minor upper respiratory tract infections, and minor skin infections), mycobacterial infection (including tuberculosis [TB] or atypical mycobacterial disease) or any major episode of infection that either required hospitalization, treatment with intravenous (IV) antibiotics within 30 days of Screening, or treatment with oral antibiotics within 14 days of Screening. • Note: In the case of a known SARS-CoV-2 infection, symptoms must have completely resolved and based on Investigator assessment in consultation with the Clinical Trial Physician/Medical Monitor, there are no sequelae that would place the subject at a higher risk of receiving investigational treatment. SARS-CoV 2 testing may be conducted prior to randomization if required by and in accordance with national, local or institutional guidelines. See App C for more details. 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. Please see the
protocol for Exclusions Related to Laboratory Results and Exclusions related to Medications |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Proportion of subjects with a CDAI score < 150 at Week 12 |
|
| E.5.1.1 | 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. |
|
| E.5.2 | 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 |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 19 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 104 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Argentina |
| New Zealand |
| Switzerland |
| Bosnia and Herzegovina |
| Moldova, Republic of |
| Ukraine |
| Puerto Rico |
| Taiwan |
| Australia |
| Belarus |
| Brazil |
| Canada |
| China |
| Israel |
| Japan |
| Korea, Republic of |
| Russian Federation |
| United Kingdom |
| United States |
| Belgium |
| Bulgaria |
| Croatia |
| Czechia |
| Denmark |
| Germany |
| Ireland |
| Italy |
| Latvia |
| Norway |
| Poland |
| Romania |
| Spain |
| Türkiye |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| The end of study is defined as either the date of the last visit of the last subject to complete the safety follow-up, or the date of receipt of the last datapoint from the last subject that is required for primary or secondary analysis, as prespecified in the protocol, whichever is the later date. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 6 |
| E.8.9.1 | In the Member State concerned months | 1 |
| E.8.9.1 | In the Member State concerned days | 28 |
| E.8.9.2 | In all countries concerned by the trial years | 6 |
| E.8.9.2 | In all countries concerned by the trial months | 1 |
| E.8.9.2 | In all countries concerned by the trial days | 28 |
Print
