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Efficacy and Safety Trial of RPC1063 for Moderate to Severe Crohn's Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02531113
Recruitment Status : Completed
First Posted : August 24, 2015
Last Update Posted : February 26, 2020
Sponsor:
Information provided by (Responsible Party):
Celgene

Brief Summary:
The purpose is to determine whether RPC1063 is effective in the treatment of Crohn's disease.

Condition or disease Intervention/treatment Phase
Crohn's Disease Drug: RPC1063 Phase 2

Detailed Description:
This open-label trial is composed of two periods: Induction and Extension. All eligible patients will be enrolled into the 12-Week Induction period and receive study medication. Patients who complete the Induction period may then be eligible to enter the 100-Week Extension period where they will continue to receive study medication.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 69 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2, Multi-Center, Open-Label Induction Trial With Extension Period to Access Endoscopic Improvement and Changes in Intestinal and Serum Biomarkers in Patients With Moderately to Severely Active Crohn's Disease Receiving Oral RPC1063 as Induction Therapy
Actual Study Start Date : October 9, 2015
Actual Primary Completion Date : September 12, 2019
Actual Study Completion Date : November 28, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Crohn's Disease

Arm Intervention/treatment
Experimental: RPC1063 (Ozanimod) Drug: RPC1063
Other Name: Ozanimod




Primary Outcome Measures :
  1. Change in Simple Endoscopic Score for Crohn's Disease from baseline [ Time Frame: Week 12 ]
    The simple endoscopy score (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. Each of these components are scored on a scale of 0 to 3. In the SES-CD, each of these 4 components are assessed in the five segments of the ileum and colon: ileum, right, transverse, left (descending and sigmoid), and rectum. The SES-CD is the sum of the individual scores of each of the components across the five segments. Mild CD is defined as an SES-CD≥3 but less than 7 points. Moderate to severely active CD is defined as a SES-CD of ≥7 points.

  2. Change in the Crohn's Disease Activity Index (CDAI) score from baseline [ Time Frame: Week 12 ]
    The Crohn's Disease Activity Index (CDAI) is a composite score that is used to measure the clinical activity of Crohn's disease. The CDAI uses a questionnaire with responses scored numerically and weighted. Scores range from 0 to approximately 600, with higher scores indicating greater disease activity.

  3. Proportion of patients with clinical remission based on CDAI at Week 12 [ Time Frame: Week 12 ]
    Clinical Remission is defined as a CDAI score of < 150

  4. Proportion of patients with clinical response based on CDAI at Week 12 [ Time Frame: Week 12 ]
    Clinical Response is defined as a CDAI reduction from baseline of ≥ 100 points

  5. Proportion of patients with clinical remission based on Patient-Reported Outcome (PRO2) definitions [ Time Frame: Week 12 ]
    The PRO2 is a composite score based on 2 components of the CDAI, the number of liquid or soft stools/day for 7 days and the abdominal pain (rated on a scale of 0-3) assessed for 7 days. Clinical Remission is defined as the average daily stool score ≤3 points AND average daily abdominal pain score ≤1 point

  6. Proportion of patients with clinical response based on PRO2 [ Time Frame: Week 12 ]
    Clinical Response is defined as PRO2 decrease ≥50%

  7. Proportion of patients with endoscopic remission based on SES-CD definitions [ Time Frame: Week 12 ]
    Endoscopic Remission is defined as SES-CD ≤ 4 points and a SES-CD decrease ≥ 2 points with no SES-CD sub-score >1point

  8. Proportion of patients with endoscopic response based on SES-CD definitions [ Time Frame: Week 12 ]
    Endoscopic Response is defined as a SES-CD decrease from baseline of ≥ 50%

  9. Change in intestinal mucosa histopathologic features and disease activity [ Time Frame: Week 12 ]
    Change in intestinal mucosa is determined through a biopsy.

  10. Changes in biomarkers [ Time Frame: Week 12 ]
    Change in immunohistochemistry and/or in situ hybridization (IHC/ISH). Change in Blood biomarkers. Change in Stool Biomarkers.

  11. Improvement in perianal and enterocutaneous fistulas [ Time Frame: Week 12 ]

    The assessment is based on two parameters: whether the fistula is draining and whether it's open or closed.

    This is assessment is only on patients that had a fistula at baseline.



Secondary Outcome Measures :
  1. Proportion of patients in endoscopic remission based on SES-CD definitions [ Time Frame: Week 52 ]
    Endoscopic Remission is defined as SES-CD ≤ 4 points and a SES-CD decrease ≥ 2 points with no SES-CD sub-score > 1 point

  2. Proportion of patients in endoscopic response based on SES-CD definitions [ Time Frame: Week 52 ]
    Endoscopic Response is defined as SES-CD decrease from baseline of ≥ 50%.

  3. Proportion of patients in clinical remission based on CDAI definitions [ Time Frame: Week 52 ]
    Clinical Remission is defined as CDAI score of < 150

  4. Proportion of patients in clinical remission based on PRO2 definitions [ Time Frame: Week 52 ]
    Clinical Remission is defined as Average daily stool score ≤3 points AND average daily abdominal pain score ≤ 1 point

  5. Proportion of patients in clinical response based on PRO2 definitions [ Time Frame: Week 52 ]
    Clinical Response is defined as PRO2 decrease ≥ 50%

  6. Proportion of patients in clinical remission based on CDAI and PRO2 definitions who are off corticosteroids of those on corticosteroids at baseline [ Time Frame: Week 52 ]
    Clinical Remission is defined as CDAI score of < 150. Clinical Remission is defined as Average daily stool score ≤3 points AND average daily abdominal pain score ≤1 point

  7. Proportion of patients in clinical remission based on CDAI [ Time Frame: Over time ]
    Clinical Remission is defined as CDAI score of < 150

  8. Proportion of patients in clinical response based on CDAI [ Time Frame: Over time ]
    Clinical Response is defined as CDAI reduction from baseline of ≥ 100 points

  9. Proportion of patients in clinical remission based on PRO2 definitions [ Time Frame: Over time ]
    Clinical Remission is defined as average daily stool score ≤3 points AND average daily abdominal pain score ≤1point

  10. Proportion of patients in clinical response based on PRO2 definitions [ Time Frame: Over time ]
    Clinical Response is defined as PRO2 decrease ≥ 50%

  11. Change in intestinal mucosa histopathologic features, histologic disease activity, and biomarkers [ Time Frame: Over time ]

    Histopathological features and disease activity are evaluated through a biopsy and compared to baseline.

    Here is the list of biomarkers that are measured in the mucosa, blood and stool and are compared to previous measurements and to baseline.

    Intestinal mucosa: immunohistochemistry and/or in situ hybridization (IHC/ISH) for example CD20, CD4, CD8, Foxp3, a4b7, CCR7, IFNa, IL17 Intestinal mucosa: transcript profiling (mRNA) for example IFN signature, T cell exhaustion signature, outcome signature, S1PR pathway Blood biomarkers for example C-reactive protein, d-dimer, IFNa, fibrin, collagen, elastin, and glycan fragments, fibrolysis and fibrogenesis markers Stool biomarkers for example fecal calprotectin and fibrolysis and fibrogenesis markers


  12. Change in fecal calprotectin and serum C-reactive protein (CRP) levels [ Time Frame: Over time ]
    Change is determined by comparing to previous measurements and to baseline.

  13. Improvement in perianal and enterocutaneous fistulas in those patients with fistulas at baseline [ Time Frame: Over time ]
    The assessment is based on two parameters: whether the fistula is draining and whether it's open or closed.

  14. Plasma concentration of RPC1063 and active metabolites at scheduled assessments during the treatment period [ Time Frame: Day 1, Week 4, Week 8, Week 12, Week 24, week 52, Week 160, early termination and safety follow-up ]
    PK structure and variability parameters estimated using the population modeling approach

  15. Absolute lymphocyte count (ALC) derived from hematology laboratory results [ Time Frame: Day 1, Week 4, Week 8, Week 12, Week 24, week 52, Week 160, early termination and safety follow-up ]
    PD structure and variability parameters estimated using the population modeling approach

  16. Peripheral immune cell phenotype determined by Flow cytometry [ Time Frame: Day 1 and Week 12. ]
    Changes in the levels of specific lymphocyte subsets in the circulation in response to Ozanimod are evaluated to better understand what lymphocyte subsets account for the decline in ALC

  17. Number of treatment emergent adverse events during induction and extension [ Time Frame: Up to Week 52 ]
    An AE is any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product, which that does not necessarily have a causal relationship with the investigational treatment

  18. Proportion of patients in clinical response based on CDAI definitions [ Time Frame: Week 52 ]
    Clinical Response is defined as CDAI reduction from baseline of ≥ 100 points


Other Outcome Measures:
  1. Proportion of patients in clinical response based on CDAI definitions [ Time Frame: Week 52 ]
    Clinical Response is defined as CDAI reduction from baseline of ≥ 100 points



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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

Key Inclusion Criteria:

  • Crohn's disease (CD) confirmed by endoscopy and histology
  • Active disease as evaluated by Crohn's Disease Activity Index Score and Simple Endoscopic Score for CD
  • Inadequate response to aminosalicylates, corticosteroids, immunomodulators or biologic therapy

Key Exclusion Criteria:

  • Diagnosis of ulcerative colitis or indeterminate colitis
  • Known strictures/stenosis leading to symptoms of obstruction
  • Current stoma or need for ileostomy or colostomy
  • Clinically relevant cardiovascular conditions or other relevant diseases that could impact the implementation or interpretation of the trial, or put the patient at risk
  • History of uveitis or known macular edema
  • History of colonic dysplasia

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): NCT02531113


Locations
Show Show 28 study locations
Sponsors and Collaborators
Celgene
Investigators
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Study Director: Kanthi Kollengode, MD Celgene Corporation

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Responsible Party: Celgene
ClinicalTrials.gov Identifier: NCT02531113    
Other Study ID Numbers: RPC01-2201
First Posted: August 24, 2015    Key Record Dates
Last Update Posted: February 26, 2020
Last Verified: February 2020
Additional relevant MeSH terms:
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Crohn Disease
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases