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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 : Recruiting
First Posted : March 13, 2018
Last Update Posted : October 22, 2019
Sponsor:
Information provided by (Responsible Party):
Celgene

Tracking Information
First Submitted Date  ICMJE February 26, 2018
First Posted Date  ICMJE March 13, 2018
Last Update Posted Date October 22, 2019
Actual Study Start Date  ICMJE June 27, 2018
Estimated Primary Completion Date April 30, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 8, 2019)
  • Proportion of subjects with a CDAI score of < 150 [ Time Frame: Up to approximately week 52 ]
    The Crohn's Disease Activity Index (CDAI) is a composite score that is used to measure the clinical activity of CD.
  • Proportion of subjects with a Simple Endoscopic Score for Crohn's Disease (SESCD) score decrease from baseline of ≥ 50% [ Time Frame: Up to approximately week 52 ]
    The SES-CD assesses the degree of endoscopic inflammation.
Original Primary Outcome Measures  ICMJE
 (submitted: March 12, 2018)
  • 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.
  • 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.
Change History Complete list of historical versions of study NCT03464097 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 8, 2019)
  • 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 [ Time Frame: Up to approximately week 52 ]
    Abdominal pain scores and stool frequency scores are patient reported outcomes collected from the patient diary
  • Proportion of subjects with CDAI reduction from baseline of ≥ 100 points or CDAI score of < 150 [ Time Frame: Up to approximately week 52 ]
    The Crohn's Disease Activity Index (CDAI) is a composite score that is used to measure the clinical activity of CD.
  • Proportion of subjects with a CDAI score of < 150 at both pre-randomization (Day 1) and Week 52 [ Time Frame: Up to approximately week 52 ]
    The Crohn's Disease Activity Index (CDAI) is a composite score that is used to measure the clinical activity of CD.
  • Proportion of subjects with a CDAI score of < 150 in subjects with a CDAI score < 150 at pre-randomization [ Time Frame: Up to approximately week 52 ]
    The Crohn's Disease Activity Index (CDAI) is a composite score that is used to measure the clinical activity of CD.
  • Proportion of subjects with a CDAI score < 150 in subjects off corticosteroids [ Time Frame: Up to approximately week 52 ]
    The Crohn's Disease Activity Index (CDAI) is a composite score that is used to measure the clinical activity of CD.
  • Proportion of subjects with absence of ulcers ≥ 0.5 cm with no segment with any ulcerated surface ≥10% [ Time Frame: Up to approximately week 52 ]
    Ulcer size will be measured during endoscopy, and assesses the degree of endoscopic inflammation.
  • Histologic improvement based on differences between ozanimod and placebo in histologic disease activity scores (ie, Global Histologic Disease Activity Score [GHAS] changes (Geboes, 2000)) [ Time Frame: Up to approximately week 52 ]
    Global Histologic Disease Activity score is a measure of histologic inflammation.
  • 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 and an SES-CD decrease from baseline of ≥ 50% [ Time Frame: Up to approximately week 52 ]
    Abdominal pain scores and stool frequency scores are patient reported outcomes collected from the patient diary. The SES-CD assesses the degree of endoscopic inflammation
  • Proportion of subjects with CDAI score of < 150 and SES-CD decrease from baseline of ≥ 50% [ Time Frame: Up to approximately week 52 ]
    The Crohn's Disease Activity Index (CDAI) is a composite score that is used to measure the clinical activity of CD and the SES-CD assesses the degree of endoscopic inflammation.
  • 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 and an SES-CD ≤ 4 points and a SES-CD decrease ≥2 points [ Time Frame: Up to approximately week 52 ]
    Abdominal pain scores and stool frequency scores are patient reported outcomes collected from the patient diary. The SES-CD assesses the degree of endoscopic inflammation.
  • Proportion of subjects with CDAI reduction from baseline of ≥ 100 points or CDAI score < 150 and SES-CD decrease from baseline of ≥ 50% [ Time Frame: Up to approximately week 52 ]
    The Crohn's Disease Activity Index (CDAI) is a composite score that is used to measure the clinical activity of CD and the SES-CD assesses the degree of endoscopic inflammation.
  • Proportion of subjects with CDAI score < 150 at Week 12 and SES-CD decrease from baseline of ≥ 50% [ Time Frame: Up to approximately week 52 ]
    The Crohn's Disease Activity Index (CDAI) is a composite score that is used to measure the clinical activity of CD and the SES-CD assesses the degree of endoscopic inflammation.
  • Proportion of subjects with CDAI reduction from baseline of ≥ 70 points [ Time Frame: Up to approximately week 52 ]
    The Crohn's Disease Activity Index (CDAI) is a composite score that is used to measure the clinical activity of CD and the SES-CD assesses the degree of endoscopic inflammation
  • Proportion of subjects with mucosal healing (SES-CD ≤ 4 points and a SES-CD decrease ≥ 2 points) and histologic improvement by GHAS or Robarts Histologic Index (RHI) [ Time Frame: Up to approximately week 52 ]
    Global Histologic Disease Activity score is a measure of histologic inflammation
  • Time to relapse and exclusion of other causes of an increase in disease activity unrelated to underlying CD (eg, infections, change in medication) [ Time Frame: Up to approximately week 52 ]
    Time to relapse is defined as an increase in the CDAI score from Maintenance Day 1 of ≥ 100 points and a CDAI score > 220, SES-CD score ≥ 6 [or ≥ 4 if isolated ileal disease.
  • Proportion of subjects with a Crohn's Disease Endoscopic Index of Severity (CDEIS) decrease from baseline of ≥ 50% [ Time Frame: Up to approximately week 52 ]
    The CDEIS assesses the degree of endoscopic inflammation.
  • Proportion of adolescent subjects with Pediatric Crohn's Disease Activity Index (PCDAI) ≤ 10 points [ Time Frame: Up to approximately week 52 ]
    The PCDAI is an instrument that was developed and validated for numerical assessment of disease activity in children and adolescents with CD (Hyams, 1991). The PCDAI includes subjective patient historical information, physical examination findings, objective laboratory parameters, data on weight gain/loss, and height velocity.
  • Proportion of adolescent subjects with decrease from baseline in PCDAI score ≥15 points [ Time Frame: Up to approximately week 52 ]
    The PCDAI is an instrument that was developed and validated for numerical assessment of disease activity in children and adolescents with CD (Hyams, 1991). The PCDAI includes subjective patient historical information, physical examination findings, objective laboratory parameters, data on weight gain/loss, and height velocity.
  • Change from baseline (Induction) in Inflammatory Bowel Disease Questionnaire (IBDQ) scores (adult subjects only) [ Time Frame: Up to approximately week 52 ]
    The IBDQ is a self-administered, 32-item questionnaire concerning 4 dimensions of quality of life (Hlavaty, 2006).
  • Change from baseline (Induction) in 36-Item Short Form-36 Survey (SF-36) scores (adult subjects only) [ Time Frame: Up to approximately week 52 ]
    The medical outcomes SF-36 questionnaire provides a measure of the subject's health status. The SF-36 consists of either scaled scores, which are the weighted sums of the questions in their section.
  • Change from baseline (Induction) in Work Productivity and Activity Impairment questionnaire for Crohn's disease (WPAI-CD) scores (adult subjects only) [ Time Frame: Up to approximately week 52 ]
    The WPAI-CD (Reilly, 1993) is a validated, reliable and responsive instrument that assesses the impact of CD on work and activity during the past 7 days (Reilly, 2008).
  • Change from baseline (Induction) in EuroQol 5 dimensions questionnaire (EQ-5D) scores [ Time Frame: Up to approximately week 52 ]
    The EQ-5D (The EuroQol Group, 1990) is a validated, 6-item, self-administered instrument designed to measure generic health status.
  • Patient Global Impression of Change (PGIC) scores (adult subjects only) [ Time Frame: Up to approximately week 52 ]
    The PGIC scale evaluates all aspects of patient's health and assesses if there has been an improvement or decline in clinical status. The self-report measure PGIC reflects a patient's belief about the efficacy of treatment.
  • Differences in CD-related hospitalizations, procedures, and surgery [ Time Frame: Up to approximately week 52 ]
    Healthcare resource utilization will be evaluated in this study to assess the impact of CD and health-related outcomes (hospitalizations, emergency department or urgent care clinic visits, procedures, and physician visits).
  • Proportion of subjects with CDAI reduction from baseline of ≥ 100 points at Week 52 or CDAI score < 150 in subjects who had previously received biologic treatment. [ Time Frame: Up to approximately week 52 ]
    The Crohn's Disease Activity Index (CDAI) is a composite score that is used to measure the clinical activity of CD.
  • Assessment of circulating lymphocyte concentration [ Time Frame: Up to approximately week 52 ]
    T and B cell panels consisting of Treg cells, naïve T and B cells, memory cells and plasmablasts are evaluated for assessment of immune status.
  • Assessment of gene expression [ Time Frame: Up to approximately week 52 ]
    Interferon signature are assessed in the blood and in colon biopsies to evaluate differences based on disease activity.
  • Assessment of protein biomarker concentration [ Time Frame: Up to approximately week 52 ]
    Protein biomarkers such as high-density lipoprotein, C-reactive protein, fecal calprotectin, Immunoglobulin A (IgA) are measured in addition to assessing clinical endpoints to help evaluate disease activity.
  • Assessment of pharmacogenetics [ Time Frame: Up to approximately week 52 ]
    Markers such as Interferon Regulatory Factor 5 are evaluated to better understand genetic variations that could lead to differences in response to Ozanimod.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 12, 2018)
  • 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.
  • 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.
  • 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
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • Mucosal healing at Week 40 [ Time Frame: Up to approximately week 40 ]
    Mucosal healing is measured by histologic inflammation
  • Time to relapse [ Time Frame: Up to approximately week 40 ]
    Relapse will be assessed by endoscopy and clinical symptoms
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Placebo-Controlled Study of Oral Ozanimod as Maintenance Therapy for Moderately to Severely Active Crohn's Disease
Official Title  ICMJE A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of Oral Ozanimod as Maintenance Therapy for Moderately to Severely Active Crohn's Disease
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Crohn Disease
Intervention  ICMJE
  • Drug: Ozanimod
    Ozanimod
  • Other: Placebo
    Placebo
Study Arms  ICMJE
  • Experimental: Administration of oral Ozanimod 0.92mg
    Subjects will receive a single 0.92 mg capsule [equivalent to ozanimod HCl 1 mg] once daily x 52 weeks
    Intervention: Drug: Ozanimod
  • Placebo Comparator: Administration of Placebo
    Subjects will receive placebo capsule orally once daily x 52 weeks
    Intervention: Other: Placebo
  • Experimental: Administration of oral Ozanimod 0.46mg
    Subjects will receive a single 0.46 mg capsule [equivalent to ozanimod HCl .5 mg] once daily x 52 weeks
    Intervention: Drug: Ozanimod
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 8, 2019)
535
Original Estimated Enrollment  ICMJE
 (submitted: March 12, 2018)
485
Estimated Study Completion Date  ICMJE August 31, 2021
Estimated Primary Completion Date April 30, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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) and/or clinical remission (CDAI score of < 150 points) and/or has an average daily stool frequency score ≤ 3 and an average abdominal pain score ≤ 1 with abdominal pain and stool frequency no worse than baseline 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 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).

    Exclusions Related to Medications:

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

    a. rectal steroid therapy (ie, steroids administered to the rectum or sigmoid via foam or enema) b. post-baseline initiation of, or increase in, corticosteroids to treat worsening CD to a dose greater than the maximum daily dose taken between the screening and baseline visits c. rectal 5-ASA (ie, 5-ASA steroids administered to the rectum) d. parenteral corticosteroids e. total parenteral nutrition therapy f. antibiotics for the treatment of CD g. immunomodulatory agents (6-MP, azathioprine, including but not limited to cyclosporine, mycophenolate mofetil, tacrolimus, and sirolimus) h. immunomodulatory biologic agents as well as other treatments for CD such asetrasimod, filgotinib, and upadacitinib I. investigational agents j. apheresis

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years to 75 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Associate Director Clinical Trial Disclosure 1-888-260-1599 clinicaltrialdisclosure@celgene.com
Listed Location Countries  ICMJE Argentina,   Australia,   Austria,   Belarus,   Belgium,   Bosnia and Herzegovina,   Brazil,   Bulgaria,   Canada,   China,   Croatia,   Czechia,   Denmark,   Finland,   Georgia,   Germany,   Greece,   Hungary,   Ireland,   Israel,   Italy,   Korea, Republic of,   Latvia,   Lithuania,   Mexico,   Moldova, Republic of,   Netherlands,   Norway,   Poland,   Portugal,   Romania,   Russian Federation,   Saudi Arabia,   Serbia,   Slovakia,   Slovenia,   South Africa,   Spain,   Sweden,   Switzerland,   Taiwan,   Turkey,   Ukraine,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03464097
Other Study ID Numbers  ICMJE RPC01-3203
U1111-1203-8002 ( Registry Identifier: WHO )
2017-004294-14 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Celgene
Study Sponsor  ICMJE Celgene
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Jerry Liu, MD Celgene Corporation
PRS Account Celgene
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP