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A Placebo-Controlled Study of Oral Ozanimod as Maintenance Therapy for Moderately to Severely Active Crohn's Disease

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ClinicalTrials.gov Identifier: NCT03464097
Recruitment Status : Not yet recruiting
First Posted : March 13, 2018
Last Update Posted : July 6, 2018
Sponsor:
Information provided by (Responsible Party):
Celgene

Brief Summary:
This is a Phase 3, randomized, double-blind, placebo-controlled study to demonstrate the effect of oral ozanimod as maintenance therapy in subjects with moderately to severely active Crohn's Disease.

Condition or disease Intervention/treatment Phase
Crohn Disease Drug: Ozanimod Other: Placebo Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 485 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A PHASE 3, MULTI CENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF ORAL OZANIMOD AS MAINTENANCE THERAPY FOR MODERATELY TO SEVERLY ACTIVE CROHN's DISEASE
Estimated Study Start Date : July 31, 2018
Estimated Primary Completion Date : January 31, 2021
Estimated Study Completion Date : January 31, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Crohn's Disease

Arm Intervention/treatment
Experimental: Administration of oral Ozanimod
Subjects will receive a single 0.92 mg capsule [equivalent to ozanimod HCl 1 mg] once daily x 40 weeks
Drug: Ozanimod
Ozanimod

Placebo Comparator: Administration of Placebo
Subjects will receive placebo capsule orally once daily x 40 weeks
Other: Placebo
Placebo




Primary Outcome Measures :
  1. Proportion of subjects with a CDAI score of < 150 at Week 40 [ Time Frame: Up to approximately week 40 ]
    The Crohn's Disease Activity Index (CDAI) is a composite score that is used to measure the clinical activity of CD.

  2. Proportion of subjects with a Simple Endoscopic Score for Crohn's Disease (SES-CD) score decrease from baseline of ≥ 50% at Week 40 [ Time Frame: Up to approximately week 40 ]
    The simple endoscopy score (SES-CD) assesses the degree of endoscopic inflammation.


Secondary Outcome Measures :
  1. Proportion of subjects with average daily abdominal pain score ≤ 1 point, average daily stool frequency score ≤ 3, and stool frequency no worse than baseline at week 40. [ Time Frame: Up to approximately week 40 ]
    Abdominal pain scores and stool frequency scores are patient reported outcomes collected from the patient diary.

  2. Proportion of subjects with CDAI reduction from baseline of ≥ 100 points or CDAI score of < 150 at Week 40 [ Time Frame: Up to approximately week 40 ]
    The Crohn's Disease Activity Index (CDAI) is a composite score that is used to measure the clinical activity of CD.

  3. Proportion of subjects with a CDAI score of < 150 at both pre-randomization and Week 40 [ Time Frame: Up to approximately week 40 ]
    The Crohn's Disease Activity Index (CDAI) is a composite score that is used to measure the clinical activity of CD

  4. Proportion of subjects with a CDAI score of < 150 at Week 40 in subjects in with a CDAI score < 150 at pre-randomization [ Time Frame: Up to approximately week 40 ]
    The Crohn's Disease Activity Index (CDAI) is a composite score that is used to measure the clinical activity of CD.

  5. Proportion of subjects with a CDAI score < 150 in subjects off corticosteroids at Week 40 [ Time Frame: Up to approximately week 40 ]
    The Crohn's Disease Activity Index (CDAI) is a composite score that is used to measure the clinical activity of CD.

  6. Proportion of subjects with absence of ulcers ≥ 0.5 cm with no segment with any ulcerated surface ≥10% at Week 40 [ Time Frame: Up to approximately week 40 ]
    Ulcer size will be measured during endoscopy, and assesses the degree of endoscopic inflammation.

  7. Proportion of subjects with histological improvement (ie. as measured by Global Histologic Disease Activity score changes (Geboes, 2000) at Week 40 [ Time Frame: Up to approximately week 40 ]
    Global Histologic Disease Activity score is a measure of histologic inflammation.

  8. Proportion of subjects with CDAI score of < 150 and SES-CD decrease from baseline of ≥ 50% at Week 40 [ Time Frame: Up to approximately week 40 ]
    The Crohn's Disease Activity Index (CDAI) is a composite score that is used to measure the clinical activity of CD. The simple endoscopy score (SES-CD) assesses the degree of endoscopic inflammation.

  9. Proportion of subjects with CDAI reduction from baseline of ≥ 70 points at Week 40 [ Time Frame: Up to approximately week 40 ]
    The Crohn's Disease Activity Index (CDAI) is a composite score that is used to measure the clinical activity of CD.

  10. Mucosal healing at Week 40 [ Time Frame: Up to approximately week 40 ]
    Mucosal healing is measured by histologic inflammation

  11. Time to relapse [ Time Frame: Up to approximately week 40 ]
    Relapse will be assessed by endoscopy and clinical symptoms

  12. Proportion of subjects with a Crohn's Disease Endoscopic Index of Severity (CDEIS) decrease from baseline of ≥ 50% at Week 52 [ Time Frame: Up to approximately week 52 ]
    CDEIS (Crohn's Disease Endoscopic Index of Severity) is an index for determining the severity of Crohn's disease with endoscopic localization to ileum and colon. CDEIS score considers 4 parameters (deep ulcerations, superficial ulcerations, surface involved by disease, and surface involved by ulcerations), each one evaluated in 5 pre-defined segments of the colon (ileum, ascending colon, transverse colon, descending colon and sigmoid loop, and rectum). The score can be calculated even in case of incomplete investigations, as the results of the individual segments are divided by the number of segments investigated. The presence of stenosis, as a result of ulcer or not, increases the score at the end of the computation.

  13. Improvement in Inflammatory Bowel Disease Questionnaire (IBDQ) scores [ Time Frame: Up to approximately week 40 ]
    The IBDQ is a frequently used outcome parameter in clinical trials. The IBDQ is a responsive instrument for reflection quick change in the quality of life of patients with CD, within a 2-week period. The IBDQ has evolved into a standard for measuring disease-specific quality of life in patients with CD.

  14. Improvement in 36-Item Short Form-36 Survey (SF-36) scores [ Time Frame: Up to approximately week 40 ]
    The medical outcomes SF-36 questionnaire provides a measure of the subject's health status.

  15. Improvement in Work Productivity and Activity Impairment questionnaire for Crohn's disease (WPAI)-CD scores [ Time Frame: Up to approximately week 40 ]
    The WPAI-CD is a validated, reliable and responsive instrument that assesses the impact of CD on work and activity.

  16. Improvement in EuroQol five dimensions questionnaire (EQ-5D) scores [ Time Frame: Up to approximately week 40 ]
    The EQ-5D is a validated, 6-item, self-administered instrument designed to measure generic health status.

  17. Differences in CD-related hospitalizations and surgery [ Time Frame: Up to approximately week 40 ]
    The number of Crohn's disease related hospitalizations, surgeries, and procedures will be collected by counting healthcare resource utilization encounters, and comparing them and assessing the cost differences between ozanimod and placebo



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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Subjects must satisfy the following criteria to be enrolled in the study:

  1. Subject fulfilled the inclusion criteria at time of entry into the Induction Study (RPC01-3201 or RPC01-3202) and have completed the Week 12 efficacy assessments of the Induction Study.
  2. Subject is in clinical response (a reduction from baseline in Crohn's Disease Activity Index (CDAI) of ≥ 100 points or CDAI score of < 150 points) or in clinical remission based on an average stool frequency score ≤ 3 with a stool frequency no worse than baseline and an average abdominal pain score ≤ 1 or CDAI score of < 150 points at Week 12 of the Induction Study.

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 (β-hCG) measured prior to randomization.
  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.
  5. Subject has undergone a colectomy (partial or total), small bowel resection, or an ostomy (ie, temporary colostomy, permanent colostomy, ileostomy, or other enterostomy) since Day 1 of the Induction Studies or has developed symptomatic fistula (enterocutaneous or entero-enteral).
  6. Subject has had active cancer within 5 years including solid tumors and hematological malignancies (except basal cell and in situ squamous cell carcinomas of the skin or cervical dysplasia/cancer that have been excised and resolved) or colonic dysplasia that has not been completely removed.

    Exclusions Related to Medications:

  7. Subject has received any of the following therapies during the Induction Study:

    1. rectal steroid therapy (ie, steroids administered to the rectum or sigmoid via foam or enema)
    2. rectal 5-ASA (ie, 5-ASA steroids administered to the rectum)
    3. parenteral corticosteroids
    4. total parenteral nutrition therapy
    5. antibiotics for the treatment of CD
    6. immunomodulatory agents (6-MP, azathioprine, including but not limited to cyclosporine, mycophenolate mofetil, tacrolimus, and sirolimus)
    7. immunomodulatory biologic agents
    8. investigational agents
    9. apheresis
  8. Subject has current or planned treatment with immunomodulatory agents (eg, azathioprine, 6-MP, or methotrexate) during the Maintenance Study.
  9. Subject has chronic nonsteroidal 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).
  10. Subject has received treatment with Class Ia or Class III anti-arrhythmic drugs or treatment with 2 or more agents in combination known to prolong PR interval.
  11. Subject has received a live vaccine within 4 weeks prior to first dose of IP.
  12. Subject has received previous treatment with lymphocyte-depleting therapies (eg, Campath™, anti-CD4, cladribine, rituximab, ocrelizumab, cyclophosphamide, mitoxantrone, total body irradiation, bone marrow transplantation, alemtuzumab, or daclizumab).
  13. Subject has received previous treatment with D-penicillamine, leflunomide or thalidomide.
  14. Subject has received previous treatment with natalizumab or fingolimod.
  15. Subject has received previous treatment with cyclosporine, tacrolimus, sirolimus, or mycophenolate mofetil within 16 weeks of first dose of IP.
  16. Subject has a history of treatment with IV immune globulin (IVIg), or plasmapheresis, within 3 months prior to first dose of IP.

    Exclusions Related to Laboratory Results:

  17. Subject has ECG results showing any clinically significant abnormality at Week 12 of the Induction Study.
  18. Subject has confirmed aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 5 times the ULN
  19. Subject has a forced expiratory volume at 1 second (FEV1) or forced vital capacity (FVC) < 50% of predicted values prior to randomization.
  20. Subject has confirmed absolute lymphocyte count (ALC) < 200 cells/μL

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03464097


Contacts
Contact: Associate Director Clinical Trial Disclosure 1-888-260-1599 clinicaltrialdisclosure@celgene.com

Locations
United States, California
OM Research Not yet recruiting
Lancaster, California, United States, 93534
United States, Florida
Florida Center for Gastroenterology Not yet recruiting
Largo, Florida, United States, 33777
IMIC, Inc. Not yet recruiting
Palmetto Bay, Florida, United States, 33157
United States, Louisiana
Gastroenterology Associates, LLC Not yet recruiting
Baton Rouge, Louisiana, United States, 70809
Georgia
LTD Aversi Clinic Not yet recruiting
Tbilisi, Georgia, 0160
Sponsors and Collaborators
Celgene
Investigators
Study Director: Barrett Levesque, MD Celgene

Responsible Party: Celgene
ClinicalTrials.gov Identifier: NCT03464097     History of Changes
Other Study ID Numbers: RPC01-3203
U1111-1203-8002 ( Registry Identifier: WHO )
2017-004294-14 ( EudraCT Number )
First Posted: March 13, 2018    Key Record Dates
Last Update Posted: July 6, 2018
Last Verified: July 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Celgene:
Crohn's Disease
Crohn Disease
Oral
Ozanimod
Moderately active
Severely active
RPC01
RPC01-3203

Additional relevant MeSH terms:
Crohn Disease
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases