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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Early Phase 2 Clinical Trial of E6011 in Patients With Active Crohn's Disease

Conditions
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Crohn's Disease

Intervention / Treatment
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* Drug: E6011
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. 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. 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. 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). 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. 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. 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: Diagnosed with ulcerative colitis or indeterminate colitis. Diagnosed with gastrointestinal epithelial dysplasia. Who have an abscess or are suspected to have one. With an artificial anus, ileo-anal pouch or fistula. 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.). Who, after undergoing small bowel resection, have been diagnosed with a short bowel syndrome, which makes maintaining caloric intake difficult.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: E6011<br> | Drug: E6011<br>* E6011, infusion, intravenously.<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo, infusion, intravenously.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Clinical Response (CR) 100 (CR100) | CR100 is defined as clinical response with a decrease of greater than or equal to (>=) 100 points in CDAI score from Baseline. CDAI is a composite index consisting of weighted scoring of 8 disease variables: number of liquid stools, extent of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, haematocrit, and body weight. CDAI scores range from 0 to approximately 600, higher score indicates higher disease activity. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with CR70 and CR100 | CR70 is defined as CR with a decrease of >=70 points in CDAI score from baseline. CR100 is defined as clinical response with a decrease of >=100 points in CDAI score from baseline. CDAI is a composite index consisting of weighted scoring of 8 disease variables: number of liquid stools, extent of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, haematocrit, and body weight. CDAI scores range from 0 to approximately 600, higher score indicates higher disease activity. | Up to Week 64 | 
| Percentage of Participants With Below 150 Points (CDAI Remission Rate) | CDAI remission is defined as CDAI score below 150 points. CDAI is a composite index consisting of weighted scoring of 8 disease variables: number of liquid stools, extent of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, haematocrit, and body weight. CDAI scores range from 0 to approximately 600, higher score indicates higher disease activity. | Up to Week 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) is defined as CR with a decrease of 5 or more points in PRO2 score from baseline. Patient reported outcome 2-clinical response 8 (PRO2-CR8) is defined as CR with a decrease of 8 or more points in PRO2 score from baseline. PRO2 is a composite index consisting of weighted scoring of 2 disease variables: number of liquid stools, extent of abdominal pain. PRO2 scores range from 0 to approximately 45, higher score indicates higher disease activity. | Up to Week 64 | 
| Percentage of Participants With Below 8 Points (PRO2-remission Rate) | PRO2-remission is defined as PRO2 below 8 points. PRO2 is a composite index consisting of weighted scoring of 2 disease variables: number of liquid stools, extent of abdominal pain. PRO2 scores range from 0 to approximately 45, higher score indicates higher disease activity. | Up to Week 64 | 
| Percentage of Participants With Endoscopic Response Based on Simple Endoscopic Score for Crohn's Disease (SES-CD) Score | Endoscopic response is defined as a decrease in SES-CD of at least 50 percent (%) from baseline. SES-CD scores will be calculated by totaling the points for: size of ulcers, ulcerated surface, affected surface, and presence of stenosis. It will be graded on a 4-point scale (0-3) in each of the five segments: rectum, left colon, transverse colon, right colon, and terminal ileum. Scale goes from 0 to 60 with a higher score indicating greater severity of disease. | Week 12 | 
| Percentage of Participants With Endoscopic Remission Based on SES-CD Score | Endoscopic remission is defined as 2 or less points on SES-CD. SES-CD scores are calculated by totaling the points for: size of ulcers, ulcerated surface, affected surface, and presence of stenosis. It will be graded on a 4-point scale (0-3) in each of the five segments: Rectum, left colon, transverse colon, right colon, and terminal ileum. Scale goes from 0 to 60 with a higher score indicating greater severity of disease. | Week 12 | 
| Change From Baseline in CDAI Score | CDAI is a composite index consisting of weighted scoring of 8 disease variables: number of liquid stools, extent of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, haematocrit, and body weight. CDAI scores range from 0 to approximately 600, higher score indicates higher disease activity. | Up to Week 64 | 
| Percent Change From Baseline in CDAI score | CDAI is a composite index consisting of weighted scoring of 8 disease variables: number of liquid stools, extent of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, haematocrit, and body weight. CDAI scores range from 0 to approximately 600, higher score indicates higher disease activity. | Up to Week 64 | 
| Change From Baseline in PRO2 | PRO2 is a composite index consisting of weighted scoring of 2 disease variables: number of liquid stools, extent of abdominal pain. PRO2 scores range from 0 to approximately 45, higher score indicates higher disease activity. | Up to Week 64 | 
| Percent Change From Baseline in PRO2 | PRO2 is a composite index consisting of weighted scoring of 2 disease variables: number of liquid stools, extent of abdominal pain. PRO2 scores range from 0 to approximately 45, higher score indicates higher disease activity. | Up to Week 64 | 
| Change From Baseline in SES-CD Score | SES-CD scores will be calculated by totaling the points for: size of ulcers, ulcerated surface, affected surface, and presence of stenosis. It will be graded on a 4-point scale (0-3) in each of the five segments: rectum, left colon, transverse colon, right colon, and terminal ileum. Scale goes from 0 to 60 with a higher score indicating greater severity of disease. | Week 12 | 
| Percent Change From Baseline in SES-CD Score | SES-CD scores will be calculated by totaling the points for: size of ulcers, ulcerated surface, affected surface, and presence of stenosis. It will be graded on a 4-point scale (0-3) in each of the five segments: rectum, left colon, transverse colon, right colon, and terminal ileum. Scale goes from 0 to 60 with a higher score indicating greater severity of disease. | Week 12 | 
| Percentage of Participants who Achieved Steroid-free Remission | Steroid-free remission will be achieved through steroid dose reduction and clinical remission (CDAI remission or PRO2-remission). CDAI remission is defined as CDAI score below 150 points. PRO2-remission is defined as PRO2- score less than 8-points. CDAI is a composite index consisting of weighted scoring of 8 disease variables: number of liquid stools, extent of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, haematocrit, and body weight. CDAI scores range from 0 to approximately 600, higher score indicates higher disease activity. PRO2 is a composite index consisting of weighted scoring of 2 disease variables: number of liquid stools, extent of abdominal pain. PRO2 scores range from 0 to approximately 45, higher score indicates higher disease activity. | Up to Week 64 | 
| Percentage of Participants who Achieved Steroid-Free Improvement | Steroid-free improvement will be achieved by steroid dose reduction and CR of CR70, CR100, PRO2-CR5 or PRO2-CR8. CR70 is CR with decrease of >=70 points and CR100 is CR with decrease >=100 points in CDAI from Baseline. PRO2-CR5 is CR with decrease of >=5 points and PRO2-CR8 is CR with decrease of >=8 points from baseline. CDAI consisting of 8 disease variables: number of liquid stools, extent of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, haematocrit, and body weight. CDAI scores range from 0 to 600, higher score indicates higher disease activity. PRO2 is a composite index consisting of weighted scoring of 2 disease variables: number of liquid stools, extent of abdominal pain. PRO2 scores range from 0 to approximately 45, higher score indicates higher disease activity. | Up to Week 64 | 
| Percent Change From Baseline in Steroid Dosage in Participants Concomitantly Using Adrenocorticosteroids |  | Up to Week 64 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Crohn's Disease, E6011, Inflammatory Bowel Diseases, Gastroenteritis, Gastrointestinal tract