Induction Study #2 of Oral Ozanimod as Induction Therapy for Moderately to Severely Active Crohn's Disease

• ClinicalTrials.gov Identifier: NCT03440385
• Recruitment Status: Recruiting
• First Posted: February 21, 2018
• Last Update Posted: October 22, 2019
• Sponsor: Celgene
• Information provided by (Responsible Party): Celgene

Study Description

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.

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 675 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official 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
• Actual Study Start Date: March 7, 2018
• Estimated Primary Completion Date: March 31, 2020
• Estimated Study Completion Date: March 31, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Administration of oral Ozanimod; Subjects will receive ozanimod 0.92 mg capsule orally starting with a 7-day dose escalation	Drug: Ozanimod; Ozanimod
Placebo Comparator: Administration of Placebo; Subjects will receive placebo capsule orally starting with a 7-day dose escalation	Other: Placebo; Placebo

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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 [ 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.
7. 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% [ 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.
8. 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.
9. 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.
10. 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.
11. 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.
12. Proportion of adolescent subjects with clinical remission, defined as Pediatric Crohn's Disease Activity Index (PCDAI) ≤ 10 points [ 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.
13. 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.
14. Change from baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) scores (adult subjects only) [ 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.
15. 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.
16. 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.
17. 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.
18. 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).
19. 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.
20. 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.
21. 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.
22. 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.

Eligibility Criteria

• Ages Eligible for Study: 12 Years to 75 Years (Child, 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. 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.

Contacts and Locations

Contacts

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

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Sponsors and Collaborators

Celgene

Investigators

• Study Director: Jerry Liu, MD; Celgene Corporation

More Information

Additional Information:

Related Info 

• Responsible Party: Celgene
• ClinicalTrials.gov Identifier: NCT03440385 History of Changes
• Other Study ID Numbers: RPC01-3202; U1111-1203-7949 ( Registry Identifier: WHO ); 2017-004293-33 ( EudraCT Number )
• First Posted: February 21, 2018
• Last Update Posted: October 22, 2019
• Last Verified: October 2019

• 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; RPC01-3202

Additional relevant MeSH terms:

Crohn Disease; Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases