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

• Register: EUCTR
• Last refreshed on: 30 April 2019
• Main ID: EUCTR2017-004295-55-LV
• Date of registration: 31/01/2018
• Prospective Registration: Yes
• Primary sponsor: Celgene International II Sàrl
• Public title: Multicenter Extension Study of Oral Ozanimod in patients with Moderately to Severely Active Crohn’s Disease
• Scientific title: A Phase 3, Multicenter, Open-Label Extension Study of Oral Ozanimod for Moderately to Severely Active Crohn’s Disease
• Date of first enrolment: 21/05/2018
• Target sample size: 1200
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-004295-55
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Austria, Belarus, Belgium, Bosnia and Herzegovina, Brazil, Bulgaria, Canada, China, Croatia, Czech Republic, Denmark, Finland, France, Georgia, Germany, Greece, Hong Kong, Hungary, Ireland, Israel, Italy, Japan, Korea, Republic of, Latvia, Lithuania, Mexico, Moldova, Republic of, Netherlands, New Zealand, Norway, Poland, Portugal, Puerto Rico, Romania, Russian Federation, Saudi Arabia, Serbia, Singapore, Slovakia, Slovenia, South Africa, Spain, Sweden, Switzerland, Taiwan, Turkey, Ukraine, United Kingdom, 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:
Subjects must satisfy the following criteria to be enrolled in the study:
1. Subjects who are not in clinical response or clinical remission after completing 12 weeks in the Induction Studies RPC01-3201 or RPC01-3202, subjects who experience relapse in the Maintenance Study RPC01-3203, subjects who complete the Maintenance Study RPC01-3203, subjects who complete at least 1 year of RPC01 2201, subjects who complete Study RPC01-1201, and subjects who complete a study of ozanimod for CD and meet the criteria for participation in the RPC01-3204 Study will have the opportunity to participate in this study.
2. Must be male or female subjects aged 18 to 75 years (at Pre-baseline), inclusive.
3. Subject must provide written informed consent prior to any study- related procedures, and have the ability to comply with the Table of Events.
4. Female subjects of childbearing potential:
Must agree to practice a highly effective method of contraception throughout the study until completion of the 75-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. 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 75-day 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 1080
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 120

Exclusion criteria:
The presence of any of the following will exclude a subject from enrollment:
Exclusions Related to General Health:
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 pregnant, lactating, or has a positive urine beta human chorionic gonadotropin (ß-hCG)
3. Subject has suspected or diagnosed intra-abdominal or perianal abscess that has not been appropriately treated
4. Subject has a history of uveitis (within the last year) or clinically confirmed diagnosis of macular edema
Exclusions Related to Medications:
5. Hypersensitivity to active ingredients or excipients of ozanimod
6. Subject has received any of the following therapies since the first dose of IP in the prior ozanimod study:
•treatment with a biologic agent
•treatment with an investigational agent other than ozanimod
•treatment with D-penicillamine, leflunomide, thalidomide, natalizumab or fingolimod
•treatment with lymphocyte-depleting therapies (eg, Campath®, anti- CD4, cladribine, rituximab, ocrelizumab, cyclophosphamide, mitoxantrone, total body irradiation, bone marrow transplantation, alemtuzumab, daclizumab)
•treatment with a live vaccine or live attenuated within 4 weeks prior to Day 1 of this study
7. Subject is currently receiving or requires initiation of any of the following therapies:
•treatment with corticosteroids at a dose that exceeds the prednisone equivalent of >40 mg
•treatment with immunomodulatory agents (eg, azathioprine, 6-MP, or methotrexate)
•chronic non-steroidal anti-inflammatory drug (NSAID) use (note: occasional use of NSAIDs and acetaminophen [eg, headache, arthritis, myalgias, or menstrual cramps] and aspirin up to 325 mg/day is permitted)
•treatment with Class Ia or Class III anti-arrhythmic drugs or treatment with 2 or more agents in combination known to prolong PR interval
•treatment with breast cancer resistance protein (BCRP) inhibitors (eg, cyclosporine, eltrombopag)
8. Subject is receiving treatment with any of the following drugs or interventions within the corresponding timeframe:
- At Day 1
o CYP2C8 inhibitors (eg, gemfibrozil or clopidogrel) and inducers (eg, rifampicin)
- Two weeks prior to Pre-baseline
o Monoamine oxidase inhibitors (eg, selegiline, phenelzine)
Exclusions Related to Laboratory Results:
9. Subject has ECG results showing any clinically significant abnormality on the last ECG of the previous study
10. Liver function impairment or persisting elevations of aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 5 x upper limit of normal (ULN)
11. Subject has a forced expiratory volume (FEV1) at 1 second or forced vital capacity (FVC) < 50% of predicted values.


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

Health Condition(s) or Problem(s) studied

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

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

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-

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-

Primary Outcome(s)

Secondary Objective: Not applicable

Timepoint(s) of evaluation of this end point: Due to the open-label nature of the study and the lack of a control group, all data will be summarized and no hypothesis testing will be performed. Each efficacy endpoint will be summarized and 95% confidence intervals around the estimates may also be presented. All efficacy data will be listed.
For all proportion-based efficacy endpoints, subjects with missing efficacy data will be considered non-responders.
For continuous efficacy endpoints, subjects with missing data will have their last post baseline value carried forward.
Observed-cases analyses will also be presented for all efficacy endpoints.

Primary end point(s): Key Efficacy Endpoints:
•Proportion of subjects with a CDAI score of < 150
•Proportion of subjects with a simple endoscopy score (SES-CD)
decrease from baseline of = 50%
•Proportion of subjects with average daily abdominal pain score = 1 point, and average daily stool frequency = 3 points with abdominal pain and stool frequency no worse than baseline
•Proportion of subjects with CDAI reduction from baseline of = 100 points or CDAI score of < 150
•Proportion of subjects with absence of ulcers = 0.5 cm with no segment with any ulcerated surface = 10%
•Proportion of subjects with CDAI reduction from baseline of = 70 points
•Change from baseline in CDAI
•Proportion of subjects with CDAI reduction from baseline of = 100 points or CDAI score of < 150 and SES-CD decrease from baseline of =50%
•Proportion of subjects with CDAI score of < 150 and SES-CD = 4 points and a SES CD decrease = 2 points
•Proportion of subjects with average daily abdominal pain score = 1 point and average daily stool frequency = 3 points and a stool frequency no worse than baseline and SES-CD = 4 points and a SES-CD decrease =2 points
•Proportion of subjects with SES-CD = 4 points and a SES-CD decrease = 2 points
•Proportion of subjects with a CDAI score < 150 in subjects off corticosteroids
•Proportion of subjects with a Crohn's Disease Endoscopic Index of Severity (CDEIS) decrease from baseline of = 50%
Exploratory Endpoints:
•Proportion of subjects with average daily abdominal pain score = 1 point, average daily stool frequency = 3 points with abdominal pain and stool frequency no worse than baseline, and SES-CD decrease from baseline = 50%
•Efficacy in subjects (clinical response, clinical remission, and endoscopic improvement) as a function of baseline biomarkers (eg, C-reactive protein, fecal calprotectin, high-density lipoprotein, IgA, IL-7, collagen fragments)
•Efficacy in subjects (clinical response, clinical remission, and endoscopic improvement) as a function of change-from-baseline biomarkers (eg, C-reactive protein, fecal calprotectin, high-density lipoprotein, IgA, IL-7, collagen fragments)
•Efficacy in subjects (clinical response, clinical remission, and endoscopic improvement) as a function of biomarkers from the prior study (eg, C-reactive protein, fecal calprotectin, high-density lipoprotein, IgA, IL-7, collagen fragments, lymphocyte counts, exhaustion signature, genotype)

Main Objective: The objective of this study is to demonstrate the long-term safety and efficacy of ozanimod for the treatment of subjects with moderately to severely active CD.

Secondary Outcome(s)

Secondary end point(s): Not applicable

Timepoint(s) of evaluation of this end point: Not applicable

Secondary ID(s)

2017-004295-55-HU

RPC01-3204

Source(s) of Monetary Support

Celgene International II Sàrl

Ethics review

Status: Approved
Approval date:
Contact: