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Induction Study #1 of Oral Ozanimod as Induction Therapy for Moderately to Severely Active Crohn's Disease

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ClinicalTrials.gov Identifier: NCT03440372
Recruitment Status : Recruiting
First Posted : February 21, 2018
Last Update Posted : October 8, 2019
Sponsor:
Information provided by (Responsible Party):
Celgene

Tracking Information
First Submitted Date  ICMJE February 14, 2018
First Posted Date  ICMJE February 21, 2018
Last Update Posted Date October 8, 2019
Actual Study Start Date  ICMJE February 27, 2018
Estimated Primary Completion Date February 20, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 4, 2019)
Proportion of subjects with a CDAI score < 150 [ Time Frame: Week 12 ]
The Crohn's Disease Activity Index (CDAI) is a composite score that is used to measure the clinical activity of CD.
Original Primary Outcome Measures  ICMJE
 (submitted: February 14, 2018)
Proportion of subjects with a CDAI score < 150 at Week 12 [ Time Frame: Up to approximately week 12 ]
The Crohn's Disease Activity Index (CDAI) is a composite score that is used to measure the clinical activity of CD.
Change History Complete list of historical versions of study NCT03440372 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 4, 2019)
  • 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 [ Time Frame: Week 12 ]
    Abdominal pain scores and stool frequency scores are patient reported outcomes collected from the patient diary.
  • Proportion of subjects with a Simple Endoscopic Score for Crohn's Disease (SES-CD) score decrease from baseline of ≥ 50% [ Time Frame: Week 12 ]
    The SES-CD assesses the degree of inflammation. The SES-CD assesses the following 4 components: size of ulcers, ulcerated surface, affected surface, and presence of narrowing.
  • Proportion of subjects with CDAI reduction from baseline of ≥ 100 points or CDAI score < 150 [ Time Frame: Week 12 ]
    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 CDAI reduction from baseline of ≥ 100 points or CDAI score < 150 and SES-CD decrease from baseline of ≥ 50% [ Time Frame: Week 12 ]
    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 inflammation.
  • Proportion of subjects with CDAI score < 150 at Week 12 and SES-CD decrease from baseline of ≥ 50% [ Time Frame: Week 12 ]
    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 inflammation.
  • Proportion of subjects with an average daily abdominal pain score ≤ 1 point, and average daily stool frequency score ≤ 3 points and both no worse than baseline AND an SES-CD ≤ 4 points and decrease ≥2 points at week 12 [ Time Frame: Up to approximately week 12 ]
    Abdominal pain scores and stool frequency scores are patient reported outcomes collected from the patient diary. The SES-CD assesses the degree of inflammation.
  • Proportion of subjects with an average daily abdominal pain score ≤ 1 point, and average daily stool frequency score ≤ 3 points and both no worse than baseline AND an SES-CD decrease from baseline of ≥ 50% at week 12. [ Time Frame: Up to approximately week 12 ]
    Abdominal pain scores and stool frequency scores are patient reported outcomes collected from the patient diary. The SES-CD assesses the degree of inflammation.
  • Histologic Improvement based on differences between ozanimod and placebo in histologic disease activity scores (ie, Global Histologic Disease Activity Score changes (Geboes, 2000) [ Time Frame: Week 12 ]
    Global Histologic Disease Activity score is a measure of histologic inflammation.
  • Proportion of subjects with CDAI reduction from baseline of ≥ 70 points [ Time Frame: Week 12 ]
    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: Week 12 ]
    Ulcer size will be measured during endoscopy, and assesses the degree of endoscopic inflammation.
  • Proportion of subjects with a Crohn's Disease Endoscopic Index of Severity (CDEIS) decrease from baseline of ≥ 50% [ Time Frame: Week 12 ]
    The CDEIS assesses the degree of endoscopic inflammation.
  • Proportion of adolescent subjects with clinical remission, defined as Pediatric Crohn's Disease Activity Index (PCDAI) ≤ 10 points at week 12 [ Time Frame: Up to approximately week 12 ]
    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 clinical response, defined as a decrease in PCDAI ≥ 15 points from baseline [ Time Frame: Up to approximately week 12 ]
    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 in Inflammatory Bowel Disease Questionnaire (IBDQ) scores (adult subjects only) [ Time Frame: Up approximately Week 12 ]
    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.
  • Change from baseline in 36-Item Short Form-36 Survey (SF-36) scores (adult subjects only) [ Time Frame: Up to approximately week 12 ]
    The medical outcomes SF-36 questionnaire provides a measure of the subject's health status.
  • Change from baseline in Work Productivity and Activity Impairment questionnaire for Crohn's disease (WPAI-CD) scores (adult subjects only) [ Time Frame: Up to approximately week 12 ]
    The WPAI-CD is a validated, reliable and responsive instrument that assesses the impact of CD on work and activity.
  • Change from baseline in EuroQol 5 dimensions questionnaire (EQ- 5D) scores [ Time Frame: Up to approximately week 12 ]
    The EQ-5D is a validated, 6-item, self-administered instrument designed to measure generic health status.
  • Differences in CD-related hospitalizations, procedures, and surgery [ Time Frame: Week 12 ]
    Healthcare Resource Utilization (HRU) 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).
  • Assessment of circulating lymphocyte concentration [ Time Frame: Up to approximately week 12 ]
    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 12 ]
    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 12 ]
    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 12 ]
    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: February 14, 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 12. [ Time Frame: Up to approximately week 12 ]
    Abdominal pain scores and stool frequency scores are patient reported outcomes collected from the patient diary.
  • Proportion of subjects with a Simple Endoscopic Score for Crohn's Disease (SES-CD) decrease from baseline of ≥ 50% at Week 12 [ Time Frame: Up to approximately week 12 ]
    The SES-CD assesses the degree of endoscopic inflammation.
  • Proportion of subjects with CDAI reduction from baseline of ≥ 100 points or CDAI score < 150 at Week 12 [ Time Frame: Up to approximately week 12 ]
    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 CDAI reduction from baseline of ≥ 100 points with SES-CD decrease from baseline of ≥ 50% at Week 12 [ Time Frame: Up to approximately week 12 ]
    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 with SES-CD decrease from baseline of ≥ 50% at Week 12 [ Time Frame: Up to approximately week 12 ]
    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% at Week 12 [ Time Frame: Up to approximately week 12 ]
    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 histological improvement (ie. as measured by Global Histologic Disease Activity score changes (Geboes, 2000) at Week 12 [ Time Frame: Up to approximately week 12 ]
    Global Histologic Disease Activity score is a measure of histologic inflammation.
  • Proportion of subjects with CDAI reduction from baseline of ≥ 70 points at Week 12 [ Time Frame: Up to approximately week 12 ]
    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 12 [ Time Frame: Up to approximately week 12 ]
    Ulcer size will be measured during endoscopy, and assesses the degree of endoscopic inflammation.
  • Proportion of subjects with a Crohn's Disease Endoscopic Index of Severity (CDEIS) decrease from baseline of ≥ 50% at Week 12 [ Time Frame: Up to approximately week 12 ]
    The CDEIS assesses the degree of endoscopic inflammation.
  • Improvement in Inflammatory Bowel Disease Questionnaire (IBDQ) scores [ Time Frame: Up to approximately week 12 ]
    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 12 ]
    The medical outcomes SF-36 questionnaire provides a measure of the subject's health status.
  • Improvement in Work Productivity and Activity Impairment Questionnaire (WPAI)-CD scores [ Time Frame: Up to approximately week 12 ]
    The WPAI-CD is a validated, reliable and responsive instrument that assesses the impact of CD on work and activity.
  • Improvement in EuroQol 5 dimensions questionnaire (EQ-5D) scores [ Time Frame: Up to approximately week 12 ]
    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 12 ]
    Healthcare Resource Utilization (HRU) will be evaluated in this study to assess the impact of CD on healthcare utilization.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Induction Study #1 of Oral Ozanimod as Induction Therapy for Moderately to Severely Active Crohn's Disease
Official Title  ICMJE Induction Study #1 - A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of Oral Ozanimod as Induction Therapy for Moderately to Severely Active Crohn's Disease
Brief Summary This is a Phase 3, randomized, double-blind, placebo-controlled study to explore the effect of oral ozanimod as an induction treatment for 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
    Subjects will receive ozanimod 0.92 mg capsule orally starting with a 7-day dose escalation
    Intervention: Drug: Ozanimod
  • Placebo Comparator: Administration of Placebo
    Subjects will receive placebo capsule orally starting with a 7-day dose escalation
    Intervention: Other: Placebo
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 4, 2019)
675
Original Estimated Enrollment  ICMJE
 (submitted: February 14, 2018)
600
Estimated Study Completion Date  ICMJE April 29, 2022
Estimated Primary Completion Date February 20, 2020   (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. Aged 12-75 years 2. Crohn's disease for ≥ 3 months on endoscopy and on histological exam 3. Inadequate response or loss of response to corticosteroids, immunomodulators, and/or biologic therapy 4. Patient has met each of the following clinical and endoscopic criteria:

  1. Crohn's Disease Activity Index (CDAI) score ≥ 220 and ≤ 450.
  2. Average daily stool frequency ≥ 4 points and/or an abdominal pain of ≥ 2 points.
  3. SES-CD score of ≥ 6 (or SES-CD ≥ 4 in subjects with isolated ileal disease).

Exclusion Criteria:

The presence of any of the following will exclude a subject from enrollment or at the time point specified in the following criteria:

  1. Subject has a diagnosis of UC, indeterminate colitis, radiation colitis, or ischemic colitis, or has strictures with prestenotic dilatation, requiring procedural intervention, or with obstructive symptoms. In addition, subjects with colonic or ileal strictures that are not passable with an age-appropriate colonoscope that the endoscopist normally uses in clinical practice, or strictures in the ileum or ileocecal valve that are fibrotic in nature, will be excluded.
  2. Current stoma, ileal-anal pouch anastomosis, fistula that is likely to require, in the physician's judgement, surgical or medical intervention within 12 weeks of entry into the study, or need for ileostomy or colostomy.
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,   Belarus,   Belgium,   Bosnia and Herzegovina,   Brazil,   Bulgaria,   Canada,   Croatia,   Czechia,   Denmark,   Germany,   Ireland,   Israel,   Italy,   Korea, Republic of,   Latvia,   Mexico,   Moldova, Republic of,   Norway,   Poland,   Romania,   Russian Federation,   Saudi Arabia,   Spain,   Switzerland,   Taiwan,   Turkey,   Ukraine,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03440372
Other Study ID Numbers  ICMJE RPC01-3201
U1111-1203-7225 ( Registry Identifier: WHO )
2017-004292-31 ( 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