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Safety and Efficacy Trial of RPC1063 for Moderate to Severe Ulcerative Colitis

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: NCT02435992
Recruitment Status : Completed
First Posted : May 6, 2015
Last Update Posted : March 2, 2021
Sponsor:
Information provided by (Responsible Party):
Celgene

Tracking Information
First Submitted Date  ICMJE April 24, 2015
First Posted Date  ICMJE May 6, 2015
Last Update Posted Date March 2, 2021
Actual Study Start Date  ICMJE June 17, 2015
Actual Primary Completion Date March 27, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 26, 2021)
  • The proportion of patients in clinical remission at Week 10 (Induction Period) [ Time Frame: 10 weeks ]
    Clinical remission was defined as a Rectal Bleeding subscore (RBS) = 0 (no blood seen), a Stool Frequency subscore (SFS) ≤ 1 (and a decrease of ≥ 1 point from the Baseline Stool Frequency subscore) and Endoscopy subscore ≤ 1 (1=mild disease, 0=normal or inactive disease)
  • The proportion of patients in clinical remission at 52 weeks (Maintenance Period) [ Time Frame: 52 weeks ]
    Clinical remission was defined as a RBS = 0 (no blood seen), a ( SFS ≤ 1 (and a decrease of ≥ 1 point from the Baseline SFS) and Endoscopy subscore ≤ 1 (1=mild disease, 0=normal or inactive disease)
Original Primary Outcome Measures  ICMJE
 (submitted: May 1, 2015)
  • Clinical remission assessed by Mayo component sub-scores [ Time Frame: Week 10 ]
    Induction Period
  • Clinical remission assessed by Mayo component sub-scores [ Time Frame: Week 52 ]
    Maintenance Period
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 26, 2021)
  • The proportion of patients with a clinical response at Week 10 [ Time Frame: 10 weeks ]
    Clinical response was defined as a reduction from Baseline in the 9-point Mayo score of ≥ 2 points and ≥ 35%, and a reduction from Baseline in the Rectal Bleeding subscore of ≥ 1 point or an absolute Rectal Bleeding subscore of ≤ 1
  • The proportion of patients with endoscopic improvement at Week 10 [ Time Frame: 10 weeks ]
    Endoscopic improvement is the improvement of the appearance of the mucosa that equates to an Endoscopic Mayo subscore of ≤ 1
  • The proportion of patients with mucosal healing at Week 10 [ Time Frame: 10 weeks ]
    Mucosal healing is defined as an Endoscopy Mayo score of ≤ 1 and a Geboes index score <2.0
  • Change in Complete Mayo Score from Baseline to Week 10 [ Time Frame: 10 weeks ]
    The Complete Mayo score consists of 4 subscores (SFS, RBS, endoscopic score, and the Physician's Global Assessment (PGA))
  • Change in Partial Mayo score from Baseline to Week 10 [ Time Frame: 10 weeks ]
    The partial Mayo score is the sum of the SFS,RBS and PGA
  • Change in 9-point Mayo score from Baseline to Week 10 [ Time Frame: 10 weeks ]
    The 9-point Mayo score is sum of the Rectal Bleeding subscore, Stool Frequency subscore, and the Endoscopy subscore.
  • Proportion of patients with histologic remission at Week 10 [ Time Frame: 10 weeks ]
    Histologic remission is defined as a Geboes index score < 2.0
  • Proportion of patients in clinical remission at Week 10 [ Time Frame: 10 weeks ]
    Clinical remission is defined as a Complete Mayo score of ≤2 with no individual subscore of ≤1 at week 10
  • The proportion of patients with a clinical response at Week 10 [ Time Frame: 10 weeks ]
    Clinical response is defined as a reduction from baseline in the total Mayo score of ≥ 3 points and ≥ 30%, and a reduction from baseline in the RBS of ≥ 1point or an absolute RBS of ≤ 1
  • The proportion of patients with clinical response at Week 10 who previously received anti-TNF [ Time Frame: 10 weeks ]
    Clinical response as described above but stratified by prior treatment with 1 or more TNF antagonists at dose approved for treatment of UC
  • The proportion of adult patients with clinical remission at Week 10 who previously received anti-TNF [ Time Frame: 10 weeks ]
    Clinical remission as described above but stratified by prior treatment with 1 or more TNF antagonists at dose approved for treatment of UC
  • The proportion of patients with endoscopic improvement at week 10 who previously received anti-TNF [ Time Frame: 10 weeks ]
    Endoscopic Improvement as described above but stratified by prior treatment with 1 or more TNF antagonists at dose approved for treatment of UC and did not respond initially or responded initially but lost response or were intolerant to medication.
  • Change in the SF-36 from Baseline to Week 10 [ Time Frame: 10 weeks ]
    Questionnaire to assess the Quality of life
  • Change in the EQ-5D from Baseline to Week 10 [ Time Frame: 10 weeks ]
    Quality of life questionnaire
  • Health resource utilization at Week 10 [ Time Frame: 10 weeks ]
    A questionnaire designed to capture the costs associated with the treatment of UC (including hospitalization for UC, colectomy)
  • Work productivity at Week 10 [ Time Frame: 10 weeks ]
    A questionnaire designed to capture the patient's work attendance and productivity
  • The proportion of patients with a clinical response at 52 weeks [ Time Frame: 52 weeks ]
    Clinical response is defined as a reduction from Baseline in the 9-point Mayo score of ≥ 2 points and ≥ 35%, and a reduction from Baseline in the Rectal Bleeding subscore of ≥ 1 point or an absolute Rectal Bleeding subscore of ≤ 1 at 52 weeks
  • The proportion of patients with endoscopic improvement at 52 weeks [ Time Frame: 52 weeks ]
    Endoscopic improvement is the improvement of the appearance of the mucosa that is measured by an Endoscopic Mayo subscore of ≤ 1 at 52 weeks
  • The proportion of patients with durable clinical remission [ Time Frame: 52 weeks ]
    Defined as the proportion of patients who achieve Clinical remission at Week 10 and maintain clinical remission at week 52 in all patients who entered the MP
  • The proportion of patients in clinical remission at 52 weeks in the subset of patients who were in remission at Week 10 [ Time Frame: 52 weeks ]
    Defined as the proportion of patients who maintain clinical remission at week 52 of all patients who achieved clinical remission at week 10
  • The proportion of adult patients with corticosteroid-free remission [ Time Frame: 52 weeks ]
    Defined as clinical remission at 52 weeks while off corticosteroids for ≥ 12 weeks
  • The proportion of adult patients with mucosal healing at 52 weeks [ Time Frame: 52 weeks ]
    Defined as an Endoscopy subscore of ≤ 1 and a Geboes index score <2.0
  • Change in Complete Mayo score from Baseline to 52 weeks [ Time Frame: 52 weeks ]
    The proportion of patients with Change in Complete Mayo score from Baseline to 52 weeks
  • Change in Partial Mayo score from Baseline to 52 weeks [ Time Frame: 52 weeks ]
    The proportion of patients with Change in Partial Mayo score from Baseline to 52 weeks
  • Change in 3-component Mayo score from Baseline to 52 weeks [ Time Frame: 52 weeks ]
    The proportion of patients with Change in 3-component Mayo score from Baseline to 52 weeks
  • The proportion of patients with histologic remission at 52 weeks [ Time Frame: 52 weeks ]
    Geboes index score < 2.0
  • The proportion of patients in clinical remission (Four-component Mayo, with different definitions) at Week 52 [ Time Frame: 52 weeks ]
    Using the 4-component Mayo score, clinical remission was defined as a RBS = 0 (no blood seen), SFS ≤ 1 and Endoscopy subscore ≤ 1 (1=mild disease, 0=normal or inactive disease) and PGA, other definitions were used
  • The proportion of patients with a clinical response (3-component Mayo with different definitions) at Week 52 [ Time Frame: 52 weeks ]
    Using the 3-component Mayo score, clinical response was defined as a reduction from baseline in the 9-point Mayo score of ≥ 2 points and ≥ 35%, and a reduction from baseline in the RBS ≥ 1 or an absolute RBS of ≤ 1 at week 52
  • The proportion of patients with clinical response at 52 weeks who previously received anti-TNF therapy [ Time Frame: 52 weeks ]
    Clinical response described as above but stratified by prior treatment with 1 or more TNF antagonists at dose approved for treatment of UC
  • The proportion of patients with clinical remission at 52 weeks who previously received anti-TNF therapy [ Time Frame: 52 weeks ]
    Clinical remission described as above but stratified by prior treatment with 1 or more TNF antagonists at dose approved for treatment of UC
  • The proportion of adult patients with endoscopic improvement at 52 weeks who previously received anti-TNF therapy [ Time Frame: 52 weeks ]
    Clinical endoscopic improvement described as above but stratified by prior treatment with 1 or more TNF antagonists at dose approved for treatment of UC
  • The proportion of adult patients in remission at 52 weeks while off corticosteroids for any length of time [ Time Frame: 52 weeks ]
    Defined as clinical remission at 52 weeks while not receiving concomitant corticosteroids.
  • Change in the SF-36 from Baseline to 52 weeks [ Time Frame: 52 weeks ]
    Questionnaire to assess the quality of life
  • Change in EQ-5D from Baseline to 52 weeks [ Time Frame: 52 weeks ]
    Questionnaire to assess the quality of life
  • Health resource utilization at 28 weeks, 40 weeks, and at 52 weeks [ Time Frame: 52 weeks ]
    A questionnaire designed to assess the costs associated with the treatment of UC (including hospitalization for UC, colectomy)
  • Work productivity at 28 weeks, 40 weeks, and at 52 weeks [ Time Frame: 52 weeks ]
    A questionnaire to assess the patient's work attendance and productivity
  • Pharmacokinetic (PK) Assessment [ Time Frame: 52 weeks ]
    To determine plasma concentration of RPC1063 and active metabolites (CC112273 and CC1084037) at scheduled assessments during the treatment period and safety follow-up visits
  • Absolute lymphocyte count (ALC) derived from blinded hematology laboratory results [ Time Frame: 52 weeks ]
    This endpoint will be summarized by Baseline, week 10,18,28,40,52, and last available measurement in Maintenance Period
  • Change in Plasma protein (cytokines, chemokines, and other markers of inflammation) from baseline to 52 weeks [ Time Frame: 52 weeks ]
    This endpoint will be summarized by Baseline, week 10,18,28,40,52, and last available measurement in Maintenance Period
  • Change in CRP from baseline to 52 weeks [ Time Frame: 52 weeks ]
    This endpoint will be summarized by Baseline, week 10,52 and last available measurement in Maintenance Period
  • Change in Fecal calprotectin from baseline to 52 weeks [ Time Frame: 52 Weeks ]
    his endpoint will be summarized by Baseline, week 10,52 and last available measurement in Maintenance Period
  • Assessment of Safety and Tolerability [ Time Frame: 52 weeks ]
    Safety and tolerability as assessed by the incidence, type of adverse events and serious adverse events as well as evaluations of vital signs, laboratory results, electrocardiogram results, and physical examination findings
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy Trial of RPC1063 for Moderate to Severe Ulcerative Colitis
Official Title  ICMJE A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Trial of Oral RPC1063 as Induction and Maintenance Therapy for Moderate to Severe Ulcerative Colitis
Brief Summary The purpose of this study is to determine whether RPC1063 is effective in the treatment of Ulcerative Colitis (UC).
Detailed Description The trial is composed of 2 periods: Induction and Maintenance. In the Induction Period (IP), patients will be entered into the trial in 3 separate cohorts (Cohort 1 and Cohort 2 for adults, Cohort 3 for adolescents). Patients from Cohort 1, 2, and 3 in clinical response at the end of the IP will proceed through to the Maintenance Period (MP). Patients from Cohort 1, 2, and 3 who participate in this trial may also qualify to participate in an optional Open-Label Extension (OLE) trial.
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 Ulcerative Colitis
Intervention  ICMJE
  • Drug: RPC1063
  • Drug: Placebo
Study Arms  ICMJE
  • Experimental: RPC1063 (Ozanimod)
    1mg, daily oral administration during Induction and Maintenance periods.
    Intervention: Drug: RPC1063
  • Placebo Comparator: Placebo
    Daily oral administration during Induction and Maintenance periods.
    Intervention: Drug: 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 Completed
Actual Enrollment  ICMJE
 (submitted: April 29, 2020)
1012
Original Estimated Enrollment  ICMJE
 (submitted: May 1, 2015)
900
Actual Study Completion Date  ICMJE June 17, 2020
Actual Primary Completion Date March 27, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Aged 18 to 75 years (at screening for Cohort 1 and 2)
  • Male or female adolescent patients aged 12 to < 18 years (at screening) with a body weight greater than or equal to 45 kg
  • UC confirmed on endoscopy
  • Moderately to severely active UC (May score 6-12)
  • Currently receiving treatment with aminosalisylate, prednisone, or budesonide
  • Can be receiving azathioprine, mercaptopurine, or methotrexate, but treatment will be stopped prior to randomization

Exclusion Criteria:

  • Have severe extensive colitis as evidence by:
  • Physician judgment that the patient is likely to require colectomy or ileostomy within 12 weeks of baseline.
  • Current or recent (within 3 months) evidence of fulminant colitis, toxic megacolon, or bowel perforation.
  • Diagnosis of CD, indeterminate colitis, or the presence of fistula consistent with CD or microscopic colitis, radiation colitis, or ischemic colitis
  • 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 unknown macular edema
  • Pregnancy, lactation, or a positive serum β-human chorionic gonadotropin (β-hCG) measured during screening
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 information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Austria,   Belarus,   Belgium,   Bulgaria,   Canada,   Croatia,   Czechia,   Georgia,   Germany,   Greece,   Hungary,   Israel,   Italy,   Korea, Republic of,   Latvia,   Moldova, Republic of,   Netherlands,   New Zealand,   Poland,   Romania,   Russian Federation,   Serbia,   Slovakia,   South Africa,   Spain,   Ukraine,   United Kingdom,   United States
Removed Location Countries Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT02435992
Other Study ID Numbers  ICMJE RPC01-3101
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Celgene
Study Sponsor  ICMJE Celgene
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: AnnKatrin Petersen, M.D., MSc. Celgene
PRS Account Celgene
Verification Date February 2021

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