Multicenter Study of Oral Ozanimod as Induction Therapy in patients with Moderately to Severely Active Crohn’s Disease
- Conditions
- Moderately to Severely Active Crohn’s DiseaseMedDRA version: 20.0Level: PTClassification code 10011401Term: Crohn's diseaseSystem Organ Class: 10017947 - Gastrointestinal disordersTherapeutic area: Diseases [C] - Digestive System Diseases [C06]
- Registration Number
- EUCTR2017-004293-33-AT
- Lead Sponsor
- Celgene International II Sàrl
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 600
1. Male or female subjects aged 18 to 75 years (at Screening)
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 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, TNFa 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 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 Scr
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 ß-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 history 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 either required hospitalization or treatment with 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
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, endoscopic response, endoscopic remission, and histologic improvement<br>- 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)<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 with abdominal pain and stool frequency 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