A Study of E6011 in Participants With Active Crohn's Disease

EA Pharma Co., Ltd.25 enrolled

Overview

The primary purpose of this study is to examine the efficacy and safety of E6011 at 12 weeks after administration by means of double-blind placebo-controlled trial.

Participants with moderate to severe Crohn's disease will be enrolled in this study. The study will include screening period, remission-induction period (double-blind), rescue period (open-label), extension period (open-label), post-observation period, and a follow-up period. At the end of remission-induction period, participants with reduction in Crohn's disease activity index (CDAI) score of 70 points or more when compared to baseline will move on to the open-label extension period, and participants with less than 70 points reduction in CDAI score will move on to the rescue period. At the end of the rescue period, participants with a reduction in the CDAI of 70 points or more will move on to the open-label extension period and with less than 70 points reduction in the CDAI score will be discontinued. The post-observation period will include in-person assessment after the completion or discontinuation of the extension period, and participants will be contacted by telephone, etc. after the last dose of study drug administration. Participants will be contacted over phone after the last dose of study drug administration for follow up assessments.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Crohn's Disease

Interventions

E6011DRUG

E6011, infusion, intravenously.

PlaceboDRUG

Placebo, infusion, intravenously.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 64 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Has diagnosed on basis of clinical findings, endoscopic findings, etc. with small intestine-type, small and large-intestine type, or large-intestine type Crohn's disease at least 12 weeks before giving consent. 2. With a baseline (at week 0 before the start of investigational medicinal product \[IMP\] administration) disease severity ranging from moderate to severe. CDAI score between 220 and 450, and a PRO2 score between 14 and 34. 3. With a SES-CD \>=7 (or for participants with isolated ileal disease, \>=4 in ileum segment) in the screening period, with one or more ulcers (in SES-CD score, ulcer presence subscore \>=1 in any segment) assessed by colonoscopy and confirmed by a centralised review. 4. Who received adrenocorticosteroids or immunomodulators in the past, but showed no therapeutic response (insufficient response) or the drugs were not tolerated (intolerance). Alternatively, participants who cannot taper adrenocorticosteroids (dependence). Alternatively, participants who showed no therapeutic response after administering biologic(s) (primary nonresponse), participants who initially showed therapeutic response but it lessened or disappeared afterwards (secondary nonresponse), or participants who did not tolerate the drug (intolerance). 5. If the participants are taking aminosalicylic acid (5-ASA), salazosulfapyridine, or antibiotics for the treatment of Crohn's disease (metronidazole, ciprofloxacin, etc.), the dosage and administration have not changed for at least 4 weeks prior to the start of the IMP administration. 6. If the participants are taking under 30 milligram per day (mg/day) of oral prednisolone (or equivalent adrenocorticosteroid) or 9 mg/day or less of oral budesonide, the dosage and administration have not changed for at least 4 weeks prior to the start of the IMP administration. 7. If the participants are taking azathioprine (AZP), 6-mercaptopurine (6-MP) or methotrexate (MTX), the dosage and administration have not changed for at least 8 weeks prior to the start of the IMP administration. Exclusion Criteria: 1. Diagnosed with ulcerative colitis or indeterminate colitis. 2. Diagnosed with gastrointestinal epithelial dysplasia. 3. Who have an abscess or are suspected to have one. 4. With an artificial anus, ileo-anal pouch or fistula. 5. With symptomatic or high-grade gastrointestinal stenosis (participants who require expansion by endoscopy or who require have SES-CD score stenosis sub-score of 3, etc.). 6. Who, after undergoing small bowel resection, have been diagnosed with a short bowel syndrome, which makes maintaining caloric intake difficult.

Locations (46)

Outcomes

Primary Outcomes

Percentage of Participants With Clinical Response (CR) 100 (CR100) at Week 12

CR100 was defined as clinical response with a reduction of greater than or equal to (\>=) 100 points in CDAI score from baseline. The CDAI system was a composite index of 8 disease activity variables: severity of abdominal pain, general well-being, very soft/liquid stool frequency, extra-intestinal symptoms, need for antidiarrheal drugs, presence of an abdominal mass, body weight and hematocrit. The sub scores of abdominal pain (0-3), general well-being (0-4, higher values mean worse well-being), and number of very soft or liquid stools were then summed. Additionally, the remaining predictors were also noted and weighted to create the total CDAI score which ranged from 0-600 with a higher score indicating a worse outcome.

Time frame: At Week 12

Secondary Outcomes

Percentage of Participants With CR70 and CR100

CR70 was defined as CR with a reduction of \>=70 points in CDAI score from baseline. CR100 was defined as clinical response with a reduction of \>=100 points in CDAI score from baseline. The CDAI system was a composite index of 8 disease activity variables: severity of abdominal pain, general well-being, very soft/liquid stool frequency, extra-intestinal symptoms, need for antidiarrheal drugs, presence of an abdominal mass, body weight and hematocrit. The sub scores of abdominal pain (0-3), general well-being (0-4, higher values mean worse well-being), and number of very soft or liquid stools were then summed. Additionally, the remaining predictors were also noted and weighted to create the total CDAI score which ranged from 0-600 with a higher score indicating a worse outcome.

Time frame: At Weeks 2, 4, 8, 12, 14, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60 and 64

Percentage of Participants With Below 150 CDAI Points

CDAI remission was defined as CDAI score below (\<) 150 points. The CDAI system was a composite index of 8 disease activity variables: severity of abdominal pain, general well-being, very soft/liquid stool frequency, extra-intestinal symptoms, need for antidiarrheal drugs, presence of an abdominal mass, body weight and hematocrit. The sub scores of abdominal pain (0-3), general well-being (0-4, higher values mean worse well-being), and number of very soft or liquid stools were then summed. Additionally, the remaining predictors were also noted and weighted to create the total CDAI score which ranged from 0-600 with a higher score indicating a worse outcome.

Data from ClinicalTrials.gov

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49, CCR Ostrava, s.r.o

Ostrava, Czechia

15, University of Debrecen Clinical Centre

Debrecen, Hungary

19, Semmelweis university

Győr, Hungary

Nagoya, Aichi-ken, Japan

Toyota, Aichi-ken, Japan

Abiko, Chiba, Japan

Kashiwa, Chiba, Japan

Kitakyushu, Fukuoka, Japan

Kasamatsuchō, Gifu, Japan

...and 36 more locations

Time frame: At Weeks 2, 4, 8, 12, 14, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60 and 64

Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2)

Patient reported outcome 2-clinical response 5 (PRO2-CR5) was defined as CR with a reduction of 5 or more points in PRO2 score from baseline. Patient reported outcome 2-clinical response 8 (PRO2-CR8) was defined as CR with a reduction of 8 or more points in PRO2 score from baseline. The PRO2 scale is a patient-reported outcome measure specifically used to assess the severity of Crohn's disease. It is derived from the CDAI and focuses on two main symptoms: abdominal pain and stool frequency. Participants rate their abdominal pain on a scale from 0 (none) to 3 (severe) and report the number of soft or liquid stools they have per day, which are then multiplied by a factor of 2 and 5, respectively. The scores from these two components are combined to give an overall PRO2 score ranging from 0 to no upper limit, with a higher score=worse outcome.

Time frame: At Weeks 2, 4, 8, 12, 14, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60 and 64

Percentage of Participants With Below 8 Points in PRO2

The PRO2 scale is a patient-reported outcome measure specifically used to assess the severity of Crohn's disease. It is derived from the CDAI and focuses on two main symptoms: abdominal pain and stool frequency. Participants rate their abdominal pain on a scale from 0 (none) to 3 (severe) and report the number of soft or liquid stools they have per day, which are then multiplied by a factor of 2 and 5, respectively. The scores from these two components are combined to give an overall PRO2 score ranging from 0 to no upper limit, with a higher score=worse outcome.

Time frame: At Weeks 2, 4, 8, 12, 14, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60 and 64

Percentage of Participants With at Least 50 Percent (%) Improvement in (Endoscopic Response) Simple Endoscopic Score for Crohn's Disease (SES-CD) Score at Week 12

Endoscopic response was defined as a improvement in SES-CD of at least 50% from baseline. The SES-CD assesses the following 4 components: size of ulcers, ulcerated surface, affected surface, and presence of narrowing. Each of these components was scored on a scale of 0 (none/unaffected) to 3 (worst). In the SES-CD, each of these 4 components are assessed in the five segments: terminal ileum, right colon, transverse colon, left colon, and rectum. The SES-CD was the sum of the individual scores of each of the components across the five segments. The range of SES-CD scores was 0 - 12 for each segment, and 0 - 60 for the overall SES-CD score, with larger scores indicating greater severity of disease.

Time frame: At Week 12

Percentage of Participants With Less Than or Equal to (<=) 2 (Endoscopic Remission) SES-CD Score at Week 12

Endoscopic remission was defined as 2 or less points on SES-CD. The SES-CD assesses following 4 components: size of ulcers, ulcerated surface, affected surface, and presence of narrowing. Each of these components was scored on scale of 0 (none/unaffected) to 3 (worst). In SES-CD, each of these 4 components are assessed in 5 segments: terminal ileum, right colon, transverse colon, left colon, and rectum. The SES-CD was the sum of the individual scores of each of the components across the five segments. The range of SES-CD scores was 0 - 12 for each segment, and 0 - 60 for the overall SES-CD score, with larger scores indicating greater severity of disease.

Time frame: At Week 12

Change From Baseline in CDAI Score

The CDAI system was a composite index of 8 disease activity variables: severity of abdominal pain, general well-being, very soft/liquid stool frequency, extra-intestinal symptoms, need for antidiarrheal drugs, presence of an abdominal mass, body weight and hematocrit. The sub scores of abdominal pain (0-3), general well-being (0-4, higher values mean worse well-being), and number of very soft or liquid stools were then summed. Additionally, the remaining predictors were also noted and weighted to create the total CDAI score which ranged from 0-600 with a higher score indicating a worse outcome.

Time frame: Baseline, at Weeks 2, 4, 8, 12, 14, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60 and 64

Percent Change From Baseline in CDAI Score

Time frame: Baseline, at Weeks 2, 4, 8, 12, 14, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60 and 64

Change From Baseline in PRO2

Time frame: Baseline, at Weeks 2, 4, 8, 12, 14, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60 and 64

Percent Change From Baseline in PRO2

Time frame: At Weeks 2, 4, 8, 12, 14, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60 and 64

Change From Baseline in SES-CD Score at Week 12

The SES-CD assesses the following 4 components: size of ulcers, ulcerated surface, affected surface, and presence of narrowing. Each of these components was scored on a scale of 0 (none/unaffected) to 3 (worst). In the SES-CD, each of these 4 components are assessed in the five segments: terminal ileum, right colon, transverse colon, left colon, and rectum. The SES-CD was the sum of the individual scores of each of the components across the five segments. The range of SES-CD scores was 0 - 12 for each segment, and 0 - 60 for the overall SES-CD score, with larger scores indicating greater severity of disease.

Time frame: Baseline, at Week 12

Percent Change From Baseline in SES-CD Score at Week 12

Time frame: Baseline, at Week 12

Percentage of Participants Who Achieved Steroid-free Remission up to Week 64

Steroid-free remission was defined as clinical remission (CDAI remission or PRO2-remission) in participants who became steroid free through steroid reduction. CDAI remission was defined as CDAI score below 150 points. PRO2-remission was defined as PRO2- score less than 8-points. The CDAI system was a composite index of 8 disease activity variables: severity of abdominal pain, general well-being, very soft/liquid stool frequency, extra-intestinal symptoms, need for antidiarrheal drugs, presence of an abdominal mass, body weight and hematocrit. The total CDAI score ranged from 0-600 with a higher score indicating a worse outcome. Participants for PRO2 scale rate their abdominal pain on scale from 0 (none) to 3 (severe) and report the number of soft or liquid stools they have per day, which are then multiplied by a factor of 2 and 5, respectively. Scores from two components combined to give overall score ranging from 0 to no upper limit, with higher score=worse outcome.

Time frame: Up to Week 64

Percentage of Participants Who Achieved Steroid-free Improvement up to Week 64

Steroid-free clinical improvement = clinical response (CR70 response, CR100 response, PRO2-CR5 and PRO2-CR8 responses) in participants who became steroid free through steroid reduction. CR70 and CR100 = clinical response with decrease of \>=70 point and \>=100 point from baseline, respectively in CDAI. PRO2-CR5 and PRO2-CR8 = clinical response with decrease of \>=5 point and \>=8 point from baseline, respectively in PRO2. CDAI system was composite index of 8 disease activity variables. Total CDAI score ranged 0-600; higher score = worse outcome. Participants for PRO2 scale rate their abdominal pain on scale from 0 (none) to 3 (severe); report number of soft or liquid stools they have per day, which are multiplied by factor of 2 and 5, respectively. The scores from these two components are combined to give an overall PRO2 score ranging from 0 to no upper limit, with a higher score=worse outcome.

Time frame: Up to Week 64

Change From Baseline in Steroid Dosage in Participants Concomitantly Using Adrenocorticosteroids up to Week 64

Change from baseline in steroid dosage in participants concomitantly using adrenocorticosteroids up to Week 64 was reported.

Time frame: Baseline up to Week 64

Percent Change From Baseline in Steroid Dosage in Participants Concomitantly Using Adrenocorticosteroids up to Week 64

Percent change from baseline in steroid dosage in participants concomitantly using adrenocorticosteroids up to Week 64 was reported.

Time frame: Baseline up to Week 64