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

• Register: EUCTR
• Last refreshed on: 8 January 2024
• Main ID: EUCTR2017-004293-33-GR
• Date of registration: 28/02/2018
• 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: 27/04/2018
• Target sample size: 600
• 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: GSM-CT
• Affiliation: Bristol-Meyers Squibb International Corporation

• Name: GSM-CT
• Affiliation: Bristol-Meyers Squibb International Corporation

Key inclusion & exclusion criteria

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, 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 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 ap
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, 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 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.


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)

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)
- Characterize the population pharmacokinetics (PK) and PK/pharmacodynamics (PD) relationship of ozanimod
- Demonstrate the safety and tolerability of ozanimod as induction therapy

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.

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

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)

NCT03440385

2017-004293-33-HU

RPC01-3202

Source(s) of Monetary Support

Celgene Corporation

Ethics review

Status: Approved
Approval date: 27/04/2018
Contact: