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

Crohn's Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02531113
• Other study ID #: RPC01-2201
• Status: Completed
• Phase: Phase 2
• Start date: October 9, 2015
• Est. completion date: November 28, 2019

Study information

• Verified date: December 2020
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 69
• Est. completion date: November 28, 2019
• Est. primary completion date: September 12, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Crohn Disease
• Crohn's Disease

Intervention

Drug:
• RPC1063

Locations

Country	Name	City	State
Canada	LHSC Victoria Hospital	London	Ontario
Hungary	Szent Margit Korhaz	Budapest
Hungary	Tolna Megyei Balassa Janos Korhaz	Szekszárd
Poland	Santa Familia Centrum Badan, Profilaktyki i Leczenia	Lodz
Poland	GASTROMED Sp.zo.o.	Lublin
Poland	Centralny Szpital Kliniczny MSWIA	Warsaw
Poland	Centrum Zdrowia Matki, Dziecka i Mlodziezy	Warsaw
Poland	Nzoz Vivamed	Warsaw
Ukraine	Si Institute Of Gastroenterology Of Namsu Dept Of Stomach And Duodenum Diseases	Dnipropetrovsk
Ukraine	Kharkiv City Clinical Hospital 2	Kharkiv
Ukraine	Kyiv CCH #18 Dept of Proctology O. O. Bogomolets NMU	Kyiv
Ukraine	Municipal Institution of Kyiv Regional Council Kyiv Regional Clinical Hospital	Kyiv
Ukraine	Lviv Regional Clinical Hospital	Lviv
Ukraine	Vinnytsia Regional Clinical	Vinnytsia
Ukraine	CI City Hospital #1	Zaporizhia
United States	Gastroenterology Associates LLC	Baton Rouge	Louisiana
United States	Ehrhardt Clinical Research LLC	Belton	Missouri
United States	Chevy Chase Clinical Research	Chevy Chase	Maryland
United States	UC Health Clinical Trials Office	Cincinnati	Ohio
United States	Ohio State University Clinical Trials Management Office	Columbus	Ohio
United States	Gastro One	Germantown	Tennessee
United States	Florida Center for Gastroenterology	Largo	Florida
United States	DM Clinical Research	Oak Lawn	Illinois
United States	Gastroenterology Associates of Orangeburg	Orangeburg	South Carolina
United States	IMIC, Inc.	Palmetto Bay	Florida
United States	San Antonio Gastroenterology	San Antonio	Texas
United States	Atlanta Gastroenterology Specialists PC	Suwanee	Georgia
United States	Adobe Clinical Research LLC	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Celgene

Countries where clinical trial is conducted

United States,  Canada,  Hungary,  Poland,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in the Crohn's Disease Activity Index (CDAI) Score From Baseline at 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.	Baseline to Week 12
Other	Percentage of Participants With Clinical Remission Based on the Crohn's Disease Activity Index (CDAI) at 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.	Week 12
Other	Percentage of Participants Who Achieved a Clinical Response Based on Crohn's Disease Activity Index (CDAI) at 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.	Week 12
Other	Percentage of Participants Who Achieved Clinical Remission Based on Patient-Reported Outcome (PRO2) Measure Definitions at 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.	Week 12
Other	Percentage of Participants Who Achieved a Clinical Response Based on Patient Reported Outcome (PRO2) Measures From Baseline at 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.	Week 12
Other	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)	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.	Week 12
Other	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	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.	Week 12
Other	Change in Roberts Intestinal Histopathology Index From Baseline (Paired Segments) at 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.	Week 12
Other	Improvement in Perianal and Enterocutaneous Fistulas	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.	Week 12
Other	Percentage of Participants Who Achieved Endoscopic Remission Based on Simple Endoscopic Score for Crohn's Disease (SES-CD) Definitions at Week 52 - Observed Cases	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.	Week 52
Other	Percentage of Participants Who Achieved an Endoscopic Response-50 Based on Simple Endoscopic Score for Crohn's Disease (SES-CD) Definitions at 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..	Week 52
Other	Percentage of Participants Who Achieved Clinical Remission Based on the Crohn's Disease Activity Index (CDAI) at 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.	Week 52
Other	Percentage of Participants Who Achieved a Clinical Response Based on CDAI at 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.	Week 52
Other	Percentage of Participants Who Achieved Clinical Remission Based on Patient-Reported Outcome (PRO2) Measure Definitions at 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.	Week 52
Other	Percentage of Participants Who Achieved a Clinical Response Based on Patient Reported Outcome (PRO2) Measures From Baseline at 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.	Week 52
Other	Percentage of Participants in Clinical Remission Based on CDAI and PRO2 Definitions Who Were Off Corticosteroids at Week 52 of Those on Corticosteroids	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.	Week 52
Other	Percentage of Participants With Clinical Remission Based on the Crohn's Disease Activity Index (CDAI) at 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.	Weeks 4 and 8
Other	Percentage of Participants Who Achieved a Clinical Response Based on CDAI at 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.	Weeks 4 and 8
Other	Percentage of Participants Who Achieved Clinical Remission Based on Patient-Reported Outcome (PRO2) Measure Definitions at 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.	Weeks 4 and 8
Other	Percentage of Participants Who Achieved a Clinical Response Based on Patient Reported Outcome (PRO2) Measures at Weeks 4 and 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.	Weeks 4 and Week 8
Other	Percentage of Participants With RHI Healing at 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.	Week 52
Other	Change in Fecal Calprotectin (Observed Cases) at Weeks 12 and 52	Change in fecal calprotectin (observed cases) determined by comparing measurements at weeks 12 and 52 to baseline measurement.	Baseline to Weeks 12 and Week 52
Other	Change in Serum C-Reactive Protein (CRP) Levels From Baseline (Observed Cases) at Weeks 12 and 52	Change in Serum C-Reactive Protein was determined by comparing to baseline.	Baseline to Weeks 12 and 52
Other	Changes in Biomarkers: Percentage of Participants With CRP Response-10 - Non-responder Imputation	The percentage of participants with a CRP Response-10 was assessed.; CRP Response-10 is defined as C-reactive protein < 10 mg/L.	Week 12, Week 52
Other	Changes in Biomarkers: Percentage of Participants With FCP Response-250 - Non-responder Imputation	The percentage of participants with a FCP Response-250 was assessed.; FCP Response-250 is defined as Fecal calprotectin < 250 ug/g.	Week 12, Week 52
Other	Improvement in Perianal and Enterocutaneous Fistulas in Participants With Fistula's From Baseline at Weeks 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.	Baseline to Week 4 and 8
Other	Pharmacokinetic Plasma Concentration of Ozanimod	Summary of concentrations of Ozanimod in RPC01-2201 by scheduled visit.	From Day 1 to Week 52
Other	PK Plasma Concentration of Active Metabolite CC-112273	Summary of concentrations of CC-112273 in RPC01-2201 by scheduled visit.	From Day 1 to Week 52
Other	Change From Baseline in Absolute Lymphocyte Count (ALC) Derived From Hematology Laboratory Results at Weeks 4, 8 and 12	Change in Absolute Lymphocyte Count (ALC) from baseline was determined by comparied to baseline.	Baseline up to Weeks 4, 8 and 12
Primary	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.	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.	Baseline to Week 12
Secondary	The Number of Participants With Treatment Emergent Adverse Events (TEAE) During the Induction and Extension Period	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	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