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

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ClinicalTrials.gov Identifier: NCT02531113
Recruitment Status : Completed
First Posted : August 24, 2015
Results First Posted : October 8, 2020
Last Update Posted : January 22, 2021
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 (SES-CD) (Paired Segments) From Baseline at Week 12 as Determined by a Blinded Central Reader. [ Time Frame: Baseline to 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. The range of SES-CD scores is 0 - 12 for each segment, and 0 - 56 for the overall SES-CD score, with larger scores indicating greater severity of disease.


Secondary Outcome Measures :
  1. The Number of Participants With Treatment Emergent Adverse Events (TEAE) During the Induction and Extension Period [ Time Frame: From the first day of ozanimod up to 90 days after the last dose of ozanimod; mean duration of exposure of study drug was 1.305 years ]

    A TEAE = any event with an onset date on or after the first dose date, or any ongoing event on the first dose date that worsens in severity or after the first dose date and until 90 days following the last dose of study drug treatment. An AE = 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. An AE can be any unfavorable or unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product, whether or not considered related to the investigational medicinal product.

    A serious AE (experience) or reaction is any untoward medical occurrence that at any dose

    • Results in death
    • Is life-threatening
    • Requires inpatient hospitalization or prolongation of existing hospitalization
    • Results in persistent or significant disability/incapacity, or
    • Is a congenital abnormality/birth defect


Other Outcome Measures:
  1. Change in the Crohn's Disease Activity Index (CDAI) Score From Baseline at Week 12 [ Time Frame: Baseline to Week 12 ]
    The Crohn's Disease Activity Index is a composite score that is used to measure the clinical activity of Crohn's disease. The CDAI includes uses 8 components: Number of liquid or soft stools for 7 days, Abdominal pain for 7 days, General well-being for 7 days, Presence of complications, Taking diarrhea medication, Abdominal mass, Hematocrit and Percentage deviation from standard weight. Scores range from 0 to approximately 600, with higher scores indicating greater disease activity. Baseline was defined as the last non-missing record on or before the first dose of study drug.

  2. Percentage of Participants With Clinical Remission Based on the Crohn's Disease Activity Index (CDAI) at Week 12 [ Time Frame: Week 12 ]
    Clinical Remission is defined as a CDAI score of < 150. The Crohn's Disease Activity Index is a composite score that is used to measure the clinical activity of Crohn's disease. The CDAI includes uses 8 components: Number of liquid or soft stools for 7 days, Abdominal pain for 7 days, General well-being for 7 days, Presence of complications, Taking diarrhea medication, Abdominal mass, Hematocrit and Percentage deviation from standard weight. Scores range from 0 to approximately 600, with higher scores indicating greater disease activity. 95% confidence interval (CI) was created using the Clopper-Pearson Exact Method.

  3. Percentage of Participants Who Achieved a Clinical Response Based on Crohn's Disease Activity Index (CDAI) at Week 12 [ Time Frame: Week 12 ]
    Clinical Response is defined as a CDAI reduction from baseline of ≥ 100 points. The Crohn's Disease Activity Index is a composite score that is used to measure the clinical activity of Crohn's disease. The CDAI includes uses 8 components: Number of liquid or soft stools for 7 days, Abdominal pain for 7 days, General well-being for 7 days, Presence of complications, Taking diarrhea medication, Abdominal mass, Hematocrit and Percentage deviation from standard weight. Scores range from 0 to approximately 600, with higher scores indicating greater disease activity. 95% confidence interval (CI) was created using the Clopper-Pearson Exact Method.

  4. Percentage of Participants Who Achieved Clinical Remission Based on Patient-Reported Outcome (PRO2) Measure Definitions at Week 12 [ 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, stool frequency (SF) and abdominal pain (AP) (rated on a scale of 0-3) assessed for 7 days. Clinical Remission (SF and AP remission) was defined as the average daily stool score ≤3 points AND average daily abdominal pain score ≤1 point. 95% confidence interval (CI) was created using the Clopper-Pearson Exact Method.

  5. Percentage of Participants Who Achieved a Clinical Response Based on Patient Reported Outcome (PRO2) Measures From Baseline at Week 12 [ Time Frame: Week 12 ]
    Clinical response based on PRO2 was defined as PRO2 decrease of ≥50% from baseline. The PRO2 is a composite score based on 2 components of the Crohn's Disease Activity Index, 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. 95% confidence interval (CI) was created using the Clopper-Pearson Exact Method.

  6. Percentage of Participants of Participants Who Achieved Endoscopic Remission Based on Simple Endoscopic Score for Crohn's Disease (SES-CD) Definitions at Week 12 (Paired Segments) [ 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. 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. 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. The range of SES-CD scores is 0 - 12 for each segment, and 0 - 56 for the overall SES-CD score, with larger scores indicating greater severity of disease. 95% confidence interval (CI) was created using the Clopper-Pearson Exact Method.

  7. Percentage of Participants Who Achieved an Endoscopic Response-50 (Paired Segment) Based on Based on Simple Endoscopic Score for Crohn's Disease (SES-CD) Definitions at Week 12 [ Time Frame: Week 12 ]
    Endoscopic Response is defined as a SES-CD decrease from baseline of ≥ 50%. 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. 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. The range of SES-CD scores is 0 - 12 for each segment, and 0 - 56 for the overall SES-CD score, with larger scores indicating greater severity of disease. 95% confidence interval (CI) was created using the Clopper-Pearson Exact Method.

  8. Change in Roberts Intestinal Histopathology Index From Baseline (Paired Segments) at Week 12 [ Time Frame: Week 12 ]
    Changes in intestinal mucosa histopathologic features and disease activity were assessed by blinded pathologists. Robarts Histopathology Index (RHI) had a maximum total score of 165, with higher scores indicating more severe histological disease. Baseline was defined as the last non-missing record on or before the first dose of study drug.

  9. 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 was only on participants that had a fistula at baseline.

  10. Percentage of Participants Who Achieved Endoscopic Remission Based on Simple Endoscopic Score for Crohn's Disease (SES-CD) Definitions at Week 52 - Observed Cases [ 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 >1point. 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. 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. The range of SES-CD scores is 0 - 12 for each segment, and 0 - 56 for the overall SES-CD score, with larger scores indicating greater severity of disease. 95% confidence interval (CI) was created using the Clopper-Pearson Exact Method.

  11. Percentage of Participants Who Achieved an Endoscopic Response-50 Based on Simple Endoscopic Score for Crohn's Disease (SES-CD) Definitions at Week 52 [ Time Frame: Week 52 ]
    Endoscopic Response is defined as a SES-CD decrease from baseline of ≥ 50%. 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. 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. The range of SES-CD scores is 0 - 12 for each segment, and 0 - 56 for the overall SES-CD score, with larger scores indicating greater severity of disease. 95% confidence interval (CI) was created using the Clopper-Pearson Exact Method..

  12. Percentage of Participants Who Achieved Clinical Remission Based on the Crohn's Disease Activity Index (CDAI) at Week 52 [ Time Frame: Week 52 ]
    Clinical Remission is defined as a CDAI score of < 150. The CDAI includes uses 8 components: Number of liquid or soft stools for 7 days, Abdominal pain for 7 days, General well-being for 7 days, Presence of complications, Taking diarrhea medication, Abdominal mass, Hematocrit and Percentage deviation from standard weight. Scores range from 0 to approximately 600, with higher scores indicating greater disease activity. 95% confidence interval (CI) was created using the Clopper-Pearson Exact Method.

  13. Percentage of Participants Who Achieved a Clinical Response Based on CDAI at Week 52 [ Time Frame: Week 52 ]
    Clinical Response is defined as a CDAI reduction from baseline of ≥ 100 points. The CDAI includes uses 8 components: Number of liquid or soft stools for 7 days, Abdominal pain for 7 days, General well-being for 7 days, Presence of complications, Taking diarrhea medication, Abdominal mass, Hematocrit and Percentage deviation from standard weight. Scores range from 0 to approximately 600, with higher scores indicating greater disease activity. 95% confidence interval (CI) was created using the Clopper-Pearson Exact Method.

  14. Percentage of Participants Who Achieved Clinical Remission Based on Patient-Reported Outcome (PRO2) Measure Definitions at Week 52 [ Time Frame: Week 52 ]
    Clinical Remission is defined as the participants with the average daily stool score ≤3 points AND average daily abdominal pain score ≤1 point. 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.

  15. Percentage of Participants Who Achieved a Clinical Response Based on Patient Reported Outcome (PRO2) Measures From Baseline at Week 52 [ Time Frame: Week 52 ]
    Clinical response based on PRO2 was defined as PRO2 decrease of ≥50% from baseline. The PRO2 is a composite score based on 2 components of the Crohn's Disease Activity Index, 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. 95% confidence interval (CI) was created using the Clopper-Pearson Exact Method.

  16. Percentage of Participants in Clinical Remission Based on CDAI and PRO2 Definitions Who Were Off Corticosteroids at Week 52 of Those on Corticosteroids [ Time Frame: Week 52 ]
    Clinical Remission is defined as CDAI score of < 150. The 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. The weighted sum of the 8 components: Number of liquid or soft stools for 7 days, Abdominal pain for 7 days, general well-being for 7 days, presence of complications, taking diarrhea medication, abdominal mass, hematocrit and percentage deviation from standard weight. The typical range of CDAI score is 0 to > 600. 95% confidence interval (CI) was created using the Clopper-Pearson Exact Method.

  17. Percentage of Participants With Clinical Remission Based on the Crohn's Disease Activity Index (CDAI) at Weeks 4 and 8 [ Time Frame: Weeks 4 and 8 ]
    Clinical Remission is defined as a CDAI score of < 150. The CDAI is a composite score that is used to measure the clinical activity of Crohn's disease. The CDAI includes uses 8 components: Number of liquid or soft stools for 7 days, Abdominal pain for 7 days, General well-being for 7 days, Presence of complications, Taking diarrhea medication, Abdominal mass, Hematocrit and Percentage deviation from standard weight. Scores range from 0 to approximately 600, with higher scores indicating greater disease activity. 95% confidence interval (CI) was created using the Clopper-Pearson Exact Method.

  18. Percentage of Participants Who Achieved a Clinical Response Based on CDAI at Weeks 4 and 8 [ Time Frame: Weeks 4 and 8 ]
    Clinical Response is defined as a CDAI reduction from baseline of ≥ 100 points. The CDAI includes uses 8 components: Number of liquid or soft stools for 7 days, Abdominal pain for 7 days, General well-being for 7 days, Presence of complications, Taking diarrhea medication, Abdominal mass, Hematocrit and Percentage deviation from standard weight. Scores range from 0 to approximately 600, with higher scores indicating greater disease activity. 95% CI was created using the Clopper-Pearson Exact Method.

  19. Percentage of Participants Who Achieved Clinical Remission Based on Patient-Reported Outcome (PRO2) Measure Definitions at Weeks 4 and 8 [ Time Frame: Weeks 4 and 8 ]
    The PRO2 is a composite score based on 2 components of the CDAI, the number of liquid or soft stools/day for 7 days, stool frequency (SF) and abdominal pain (AP) (rated on a scale of 0-3) assessed for 7 days. Clinical Remission (SF and AP remission) was defined as the average daily stool score ≤3 points AND average daily abdominal pain score ≤1 point. 95% confidence interval (CI) was created using the Clopper-Pearson Exact Method.

  20. Percentage of Participants Who Achieved a Clinical Response Based on Patient Reported Outcome (PRO2) Measures at Weeks 4 and 8 [ Time Frame: Weeks 4 and Week 8 ]
    Clinical response based on PRO2 was defined as PRO2 decrease of ≥50%. The PRO2 is a composite score based on 2 components of the Crohn's Disease Activity Index, 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. 95% confidence interval (CI) was created using the Clopper-Pearson Exact Method.

  21. Percentage of Participants With RHI Healing at Week 52 [ Time Frame: Week 52 ]

    Changes from baseline in intestinal mucosa histopathologic features and disease activity were assessed by blinded pathologists. Robarts Histopathology Index (RHI) had a maximum total score of 165, with higher scores indicating more severe histological disease. Baseline was defined as the last non-missing record on or before the first dose of study drug.

    The Robarts Histopathology Index (RHI) is a recently validated instrument that measures histological disease activity in ulcerative colitis.

    RHI Mucosal Healing was defined as a composite endpoint of being a responder for endoscopic remission and RHI remission.


  22. Change in Fecal Calprotectin (Observed Cases) at Weeks 12 and 52 [ Time Frame: Baseline to Weeks 12 and Week 52 ]
    Change in fecal calprotectin (observed cases) determined by comparing measurements at weeks 12 and 52 to baseline measurement.

  23. Change in Serum C-Reactive Protein (CRP) Levels From Baseline (Observed Cases) at Weeks 12 and 52 [ Time Frame: Baseline to Weeks 12 and 52 ]
    Change in Serum C-Reactive Protein was determined by comparing to baseline.

  24. Changes in Biomarkers: Percentage of Participants With CRP Response-10 - Non-responder Imputation [ Time Frame: Week 12, Week 52 ]

    The percentage of participants with a CRP Response-10 was assessed.

    CRP Response-10 is defined as C-reactive protein < 10 mg/L.


  25. Changes in Biomarkers: Percentage of Participants With FCP Response-250 - Non-responder Imputation [ Time Frame: Week 12, Week 52 ]

    The percentage of participants with a FCP Response-250 was assessed.

    FCP Response-250 is defined as Fecal calprotectin < 250 ug/g.


  26. Improvement in Perianal and Enterocutaneous Fistulas in Participants With Fistula's From Baseline at Weeks 4 and 8 [ Time Frame: Baseline to Week 4 and 8 ]
    The assessment is based on two parameters: whether the fistula is draining and whether it's open or closed. This is assessment was only on participants that had a fistula at baseline.

  27. Pharmacokinetic Plasma Concentration of Ozanimod [ Time Frame: From Day 1 to Week 52 ]
    Summary of concentrations of Ozanimod in RPC01-2201 by scheduled visit.

  28. PK Plasma Concentration of Active Metabolite CC-112273 [ Time Frame: From Day 1 to Week 52 ]
    Summary of concentrations of CC-112273 in RPC01-2201 by scheduled visit.

  29. Change From Baseline in Absolute Lymphocyte Count (ALC) Derived From Hematology Laboratory Results at Weeks 4, 8 and 12 [ Time Frame: Baseline up to Weeks 4, 8 and 12 ]
    Change in Absolute Lymphocyte Count (ALC) from baseline was determined by comparied to baseline.



Information from the National Library of Medicine

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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
  Study Documents (Full-Text)

Documents provided by Celgene:
Study Protocol  [PDF] May 24, 2019
Statistical Analysis Plan  [PDF] January 16, 2020

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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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
Results First Posted: October 8, 2020
Last Update Posted: January 22, 2021
Last Verified: December 2020
Additional relevant MeSH terms:
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Crohn Disease
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Ozanimod
Sphingosine 1 Phosphate Receptor Modulators
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs