Crohn's Disease
Conditions
Keywords
Crohn's Disease, E6011, Inflammatory Bowel Diseases, Gastroenteritis, Gastrointestinal tract
Brief summary
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
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.
Interventions
DRUGE6011
E6011, infusion, intravenously.
DRUGPlacebo
Placebo, infusion, intravenously.
Sponsors
EA Pharma Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Clinical Response (CR) 100 (CR100) at Week 12 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Below 150 CDAI Points | At Weeks 2, 4, 8, 12, 14, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60 and 64 | 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. |
| Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | At Weeks 2, 4, 8, 12, 14, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60 and 64 | 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. |
| Percentage of Participants With Below 8 Points in PRO2 | At Weeks 2, 4, 8, 12, 14, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60 and 64 | 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. |
| 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 | 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. |
| Percentage of Participants With Less Than or Equal to (<=) 2 (Endoscopic Remission) SES-CD Score at Week 12 | 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. |
| Change From Baseline in CDAI Score | Baseline, at Weeks 2, 4, 8, 12, 14, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60 and 64 | 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. |
| Percent Change From Baseline in CDAI Score | Baseline, at Weeks 2, 4, 8, 12, 14, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60 and 64 | 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. |
| Percentage of Participants With CR70 and CR100 | At Weeks 2, 4, 8, 12, 14, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60 and 64 | 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. |
| Percent Change From Baseline in PRO2 | At Weeks 2, 4, 8, 12, 14, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60 and 64 | 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. |
| Change From Baseline in SES-CD Score at Week 12 | Baseline, 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. |
| Percent Change From Baseline in SES-CD Score at Week 12 | Baseline, 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. |
| Percentage of Participants Who Achieved Steroid-free Remission up to Week 64 | 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. |
| Percentage of Participants Who Achieved Steroid-free Improvement up to Week 64 | 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. |
| Change From Baseline in Steroid Dosage in Participants Concomitantly Using Adrenocorticosteroids up to Week 64 | Baseline up to Week 64 | Change from baseline in steroid dosage in participants concomitantly using adrenocorticosteroids up to Week 64 was reported. |
| Percent Change From Baseline in Steroid Dosage in Participants Concomitantly Using Adrenocorticosteroids up to Week 64 | Baseline up to Week 64 | Percent change from baseline in steroid dosage in participants concomitantly using adrenocorticosteroids up to Week 64 was reported. |
| Change From Baseline in PRO2 | Baseline, at Weeks 2, 4, 8, 12, 14, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60 and 64 | 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. |
Countries
Czechia, Hungary, Japan, Poland, Russia
Participant flow
Recruitment details
Participants took part in the study at 49 investigative sites in Japan, Czech Republic, Hungary, Poland, and Russia from 25 April 2019 to 03 April 2024.
Pre-assignment details
A total of 65 participants were screened, of which 40 were screen failures and 25 were enrolled to receive study treatment.
Participants by arm
| Arm | Count |
|---|---|
| E6011 10 mg/kg Participants with moderate to severe active Crohn's disease received E6011 10 milligram per kilogram (mg/kg), intravenous (IV) infusion once, at Weeks 0, 1, 2 then every 2 weeks up Week 10 during the Remission Induction Period, thereafter, non-responder participants continued E6011 treatment at Weeks 12, 13, 14 then every 2 weeks up to Week 22 during the Rescue Period. Responder participants at Week 12 continued E6011 treatment, every 4 weeks from Week 12 to Week 48 and responders at Week 24 continued E6011 treatment, every 4 weeks, from Week 24 to Week 60 during the Extension Period. | 12 |
| Placebo Then E6011 10 mg/kg Participants with moderate to severe active Crohn's disease received placebo, IV infusion once, at Weeks 0, 1, 2 then every 2 weeks up Week 10 during the Remission Induction Period, thereafter, non-responder participants received E6011 10 mg/kg, IV infusion once, at Weeks 12, 13, 14 then every 2 weeks up to Week 22 during the Rescue Period. Responder participants at Week 12 continued E6011 treatment, every 4 weeks from Week 12 to Week 48 and responders at Week 24 continued E6011 treatment, every 4 weeks, from Week 24 to Week 60 during the Extension Period. | 13 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Extension Period:(Week 12-52/Week 24-64) | Lack of Efficacy | 1 | 1 |
| Extension Period:(Week 12-52/Week 24-64) | Other | 3 | 2 |
| Extension Period:(Week 12-52/Week 24-64) | Progressive Disease | 1 | 0 |
| Remission-induction Period: (Weeks 0-12) | Withdrawal by Subject | 2 | 0 |
| Rescue Period: (Weeks 12 to 24) | Progressive disease | 0 | 2 |
| Rescue Period: (Weeks 12 to 24) | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Placebo Then E6011 10 mg/kg | Total | E6011 10 mg/kg |
|---|---|---|---|
| Age, Continuous | 33.2 years STANDARD_DEVIATION 12 | 31.5 years STANDARD_DEVIATION 10.5 | 29.8 years STANDARD_DEVIATION 8.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants | 25 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 9 Participants | 20 Participants | 11 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 5 Participants | 1 Participants |
| Sex: Female, Male Female | 5 Participants | 7 Participants | 2 Participants |
| Sex: Female, Male Male | 8 Participants | 18 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 13 | 0 / 5 | 0 / 7 | 0 / 7 | 0 / 8 | 0 / 12 | 0 / 13 |
| other Total, other adverse events | 6 / 12 | 5 / 13 | 3 / 5 | 4 / 7 | 1 / 7 | 5 / 8 | 2 / 12 | 1 / 13 |
| serious Total, serious adverse events | 0 / 12 | 1 / 13 | 0 / 5 | 2 / 7 | 0 / 7 | 0 / 8 | 0 / 12 | 1 / 13 |
Outcome results
Primary
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
Population: The FAS included participants to whom the IMP has been administered after randomization, and who had 1 or more evaluable, post-IMP administration primary efficacy endpoint (that is, to have an evaluable (CDAI) value at baseline and any other post baseline).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| E6011 10 mg/kg | Percentage of Participants With Clinical Response (CR) 100 (CR100) at Week 12 | 33.3 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With Clinical Response (CR) 100 (CR100) at Week 12 | 23.1 percentage of participants |
95% CI: [-24.9, 45.4]
Secondary
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
Population: FAS was used for analysis. Here n = participants who were evaluable for outcome measure at given time points. As planned, combined data for all the periods (remission-induction, rescue and extension periods) was collected and reported in outcome measure due to same dosing of E6011. From Week 14-24, participants data analyzed simultaneously for rescue and extension period and reported collectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| E6011 10 mg/kg | Change From Baseline in CDAI Score | Change at Week 32 | -97.3 score on a scale | Standard Deviation 95.1 |
| E6011 10 mg/kg | Change From Baseline in CDAI Score | Change at Week 28 | -160.7 score on a scale | Standard Deviation 28.1 |
| E6011 10 mg/kg | Change From Baseline in CDAI Score | Change at Week 36 | -136.0 score on a scale | Standard Deviation 44.2 |
| E6011 10 mg/kg | Change From Baseline in CDAI Score | Change at Week 8 | -92.8 score on a scale | Standard Deviation 109.8 |
| E6011 10 mg/kg | Change From Baseline in CDAI Score | Change at Week 40 | -173.7 score on a scale | Standard Deviation 49 |
| E6011 10 mg/kg | Change From Baseline in CDAI Score | Change at Week 2 | -38.0 score on a scale | Standard Deviation 96.1 |
| E6011 10 mg/kg | Change From Baseline in CDAI Score | Change at Week 44 | -147.3 score on a scale | Standard Deviation 75.8 |
| E6011 10 mg/kg | Change From Baseline in CDAI Score | Change at Week 12 | -92.4 score on a scale | Standard Deviation 109 |
| E6011 10 mg/kg | Change From Baseline in CDAI Score | Change at Week 48 | -127.3 score on a scale | Standard Deviation 56.1 |
| E6011 10 mg/kg | Change From Baseline in CDAI Score | Change at Week 20 | -115.4 score on a scale | Standard Deviation 66.1 |
| E6011 10 mg/kg | Change From Baseline in CDAI Score | Change at Week 52 | -103.7 score on a scale | Standard Deviation 102.8 |
| E6011 10 mg/kg | Change From Baseline in CDAI Score | Change at Week 14 | -22.0 score on a scale | Standard Deviation 78.1 |
| E6011 10 mg/kg | Change From Baseline in CDAI Score | Change at Week 4 | -60.5 score on a scale | Standard Deviation 102.7 |
| E6011 10 mg/kg | Change From Baseline in CDAI Score | Change at Week 16 | -102.8 score on a scale | Standard Deviation 95.2 |
| E6011 10 mg/kg | Change From Baseline in CDAI Score | Change at Week 24 | -115.5 score on a scale | Standard Deviation 90.1 |
| Placebo Then E6011 10 mg/kg | Change From Baseline in CDAI Score | Change at Week 52 | -171.3 score on a scale | Standard Deviation 162.4 |
| Placebo Then E6011 10 mg/kg | Change From Baseline in CDAI Score | Change at Week 56 | -211.0 score on a scale | — |
| Placebo Then E6011 10 mg/kg | Change From Baseline in CDAI Score | Change at Week 60 | -145.0 score on a scale | Standard Deviation 97.6 |
| Placebo Then E6011 10 mg/kg | Change From Baseline in CDAI Score | Change at Week 64 | -240.0 score on a scale | — |
| Placebo Then E6011 10 mg/kg | Change From Baseline in CDAI Score | Change at Week 24 | -100.0 score on a scale | Standard Deviation 120.3 |
| Placebo Then E6011 10 mg/kg | Change From Baseline in CDAI Score | Change at Week 28 | -153.1 score on a scale | Standard Deviation 93.5 |
| Placebo Then E6011 10 mg/kg | Change From Baseline in CDAI Score | Change at Week 16 | -89.3 score on a scale | Standard Deviation 120.1 |
| Placebo Then E6011 10 mg/kg | Change From Baseline in CDAI Score | Change at Week 20 | -119.1 score on a scale | Standard Deviation 136.4 |
| Placebo Then E6011 10 mg/kg | Change From Baseline in CDAI Score | Change at Week 2 | -50.3 score on a scale | Standard Deviation 56.7 |
| Placebo Then E6011 10 mg/kg | Change From Baseline in CDAI Score | Change at Week 4 | -64.5 score on a scale | Standard Deviation 91 |
| Placebo Then E6011 10 mg/kg | Change From Baseline in CDAI Score | Change at Week 8 | -70.5 score on a scale | Standard Deviation 113.3 |
| Placebo Then E6011 10 mg/kg | Change From Baseline in CDAI Score | Change at Week 12 | -69.6 score on a scale | Standard Deviation 107 |
| Placebo Then E6011 10 mg/kg | Change From Baseline in CDAI Score | Change at Week 14 | -25.8 score on a scale | Standard Deviation 100.8 |
| Placebo Then E6011 10 mg/kg | Change From Baseline in CDAI Score | Change at Week 32 | -183.7 score on a scale | Standard Deviation 79.1 |
| Placebo Then E6011 10 mg/kg | Change From Baseline in CDAI Score | Change at Week 36 | -143.0 score on a scale | Standard Deviation 109.8 |
| Placebo Then E6011 10 mg/kg | Change From Baseline in CDAI Score | Change at Week 40 | -157.0 score on a scale | Standard Deviation 84 |
| Placebo Then E6011 10 mg/kg | Change From Baseline in CDAI Score | Change at Week 44 | -185.2 score on a scale | Standard Deviation 102.9 |
| Placebo Then E6011 10 mg/kg | Change From Baseline in CDAI Score | Change at Week 48 | -209.8 score on a scale | Standard Deviation 99.2 |
Secondary
Change From Baseline 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: Baseline, at Weeks 2, 4, 8, 12, 14, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60 and 64
Population: FAS was used for analysis. Here n = participants who were evaluable for outcome measure at given time points. As planned, combined data for all the periods (remission-induction, rescue and extension periods) was collected and reported in outcome measure due to same dosing of E6011. From Week 14-24, participants data analyzed simultaneously for rescue and extension period and reported collectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| E6011 10 mg/kg | Change From Baseline in PRO2 | Change at Week 52 | -8.3 score on a scale | Standard Deviation 3.1 |
| E6011 10 mg/kg | Change From Baseline in PRO2 | Change at Week 2 | -3.1 score on a scale | Standard Deviation 6.5 |
| E6011 10 mg/kg | Change From Baseline in PRO2 | Change at Week 4 | -5.3 score on a scale | Standard Deviation 6.6 |
| E6011 10 mg/kg | Change From Baseline in PRO2 | Change at Week 8 | -6.9 score on a scale | Standard Deviation 7.3 |
| E6011 10 mg/kg | Change From Baseline in PRO2 | Change at Week 12 | -6.5 score on a scale | Standard Deviation 6.2 |
| E6011 10 mg/kg | Change From Baseline in PRO2 | Change at Week 14 | -3.0 score on a scale | Standard Deviation 6.7 |
| E6011 10 mg/kg | Change From Baseline in PRO2 | Change at Week 16 | -8.1 score on a scale | Standard Deviation 5.7 |
| E6011 10 mg/kg | Change From Baseline in PRO2 | Change at Week 20 | -7.9 score on a scale | Standard Deviation 4.2 |
| E6011 10 mg/kg | Change From Baseline in PRO2 | Change at Week 24 | -6.5 score on a scale | Standard Deviation 6.4 |
| E6011 10 mg/kg | Change From Baseline in PRO2 | Change at Week 28 | -9.0 score on a scale | Standard Deviation 1 |
| E6011 10 mg/kg | Change From Baseline in PRO2 | Change at Week 32 | -5.5 score on a scale | Standard Deviation 6.1 |
| E6011 10 mg/kg | Change From Baseline in PRO2 | Change at Week 36 | -9.0 score on a scale | Standard Deviation 7 |
| E6011 10 mg/kg | Change From Baseline in PRO2 | Change at Week 40 | -13.0 score on a scale | Standard Deviation 1.7 |
| E6011 10 mg/kg | Change From Baseline in PRO2 | Change at Week 44 | -11.0 score on a scale | Standard Deviation 2 |
| E6011 10 mg/kg | Change From Baseline in PRO2 | Change at Week 48 | -8.7 score on a scale | Standard Deviation 0.6 |
| Placebo Then E6011 10 mg/kg | Change From Baseline in PRO2 | Change at Week 20 | -8.3 score on a scale | Standard Deviation 9.2 |
| Placebo Then E6011 10 mg/kg | Change From Baseline in PRO2 | Change at Week 60 | -9.5 score on a scale | Standard Deviation 6.4 |
| Placebo Then E6011 10 mg/kg | Change From Baseline in PRO2 | Change at Week 24 | -6.9 score on a scale | Standard Deviation 7.4 |
| Placebo Then E6011 10 mg/kg | Change From Baseline in PRO2 | Change at Week 44 | -9.4 score on a scale | Standard Deviation 7.7 |
| Placebo Then E6011 10 mg/kg | Change From Baseline in PRO2 | Change at Week 52 | -11.0 score on a scale | Standard Deviation 8.5 |
| Placebo Then E6011 10 mg/kg | Change From Baseline in PRO2 | Change at Week 28 | -9.6 score on a scale | Standard Deviation 5.7 |
| Placebo Then E6011 10 mg/kg | Change From Baseline in PRO2 | Change at Week 2 | -4.3 score on a scale | Standard Deviation 4 |
| Placebo Then E6011 10 mg/kg | Change From Baseline in PRO2 | Change at Week 64 | -15.0 score on a scale | — |
| Placebo Then E6011 10 mg/kg | Change From Baseline in PRO2 | Change at Week 4 | -4.9 score on a scale | Standard Deviation 6.5 |
| Placebo Then E6011 10 mg/kg | Change From Baseline in PRO2 | Change at Week 32 | -12.0 score on a scale | Standard Deviation 6.2 |
| Placebo Then E6011 10 mg/kg | Change From Baseline in PRO2 | Change at Week 8 | -5.8 score on a scale | Standard Deviation 7.1 |
| Placebo Then E6011 10 mg/kg | Change From Baseline in PRO2 | Change at Week 48 | -11.8 score on a scale | Standard Deviation 6.6 |
| Placebo Then E6011 10 mg/kg | Change From Baseline in PRO2 | Change at Week 12 | -5.5 score on a scale | Standard Deviation 6.7 |
| Placebo Then E6011 10 mg/kg | Change From Baseline in PRO2 | Change at Week 36 | -9.0 score on a scale | Standard Deviation 6.1 |
| Placebo Then E6011 10 mg/kg | Change From Baseline in PRO2 | Change at Week 14 | -2.7 score on a scale | Standard Deviation 5.4 |
| Placebo Then E6011 10 mg/kg | Change From Baseline in PRO2 | Change at Week 56 | -13.0 score on a scale | — |
| Placebo Then E6011 10 mg/kg | Change From Baseline in PRO2 | Change at Week 16 | -6.1 score on a scale | Standard Deviation 7.6 |
| Placebo Then E6011 10 mg/kg | Change From Baseline in PRO2 | Change at Week 40 | -6.3 score on a scale | Standard Deviation 6.8 |
Secondary
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
Population: FAS was used for analysis. Here, overall number of participants analyzed ('N') = participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| E6011 10 mg/kg | Change From Baseline in SES-CD Score at Week 12 | 1.4 score on a scale | Standard Deviation 4.9 |
| Placebo Then E6011 10 mg/kg | Change From Baseline in SES-CD Score at Week 12 | -3.5 score on a scale | Standard Deviation 4.9 |
Secondary
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
Population: FAS was used for analysis. Here, N = participants who were evaluable for this outcome measure. As planned, combined data for all the periods (remission-induction, rescue, extension and post observation periods) was collected and reported in outcome measure due to same dosing of E6011.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| E6011 10 mg/kg | Change From Baseline in Steroid Dosage in Participants Concomitantly Using Adrenocorticosteroids up to Week 64 | 0 milligram per day (mg/day) | Standard Deviation 0 |
| Placebo Then E6011 10 mg/kg | Change From Baseline in Steroid Dosage in Participants Concomitantly Using Adrenocorticosteroids up to Week 64 | 0 milligram per day (mg/day) | Standard Deviation 0 |
Secondary
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
Population: FAS was used for analysis. Here, overall number of participants analyzed ('N') = participants who were evaluable for this outcome measure. As planned, combined data for all the periods (remission-induction, rescue and extension periods) was collected and reported in outcome measure due to same dosing of E6011. Steroid-free improvement was assessed in participants who were concomitantly taking adrenocorticosteroid.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| E6011 10 mg/kg | Percentage of Participants Who Achieved Steroid-free Improvement up to Week 64 | 0 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants Who Achieved Steroid-free Improvement up to Week 64 | 0 percentage of participants |
Secondary
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
Population: FAS was used for analysis. Here, overall number of participants analyzed ('N') = participants who were evaluable for this outcome measure. As planned, combined data for all the periods (remission-induction, rescue and extension periods) was collected and reported in outcome measure due to same dosing of E6011. Steroid-free remission was assessed in participants who were concomitantly taking adrenocorticosteroid.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| E6011 10 mg/kg | Percentage of Participants Who Achieved Steroid-free Remission up to Week 64 | 0 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants Who Achieved Steroid-free Remission up to Week 64 | 0 percentage of participants |
Secondary
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
Population: The FAS included participants to whom the IMP has been administered after randomization, and who had 1 or more evaluable, post-IMP administration primary efficacy endpoint (that is, to have an evaluable (CDAI) value at baseline and any other post baseline).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| E6011 10 mg/kg | 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 | 8.3 percentage of participants |
| Placebo Then E6011 10 mg/kg | 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 | 15.4 percentage of participants |
95% CI: [-32.1, 18]
Secondary
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
Population: FAS was used for analysis. Here, n = participants who were evaluable for outcome measure at given time points. As planned, combined data for all the periods (remission-induction, rescue and extension periods) was collected and reported in outcome measure due to same dosing of E6011. From Week 14-24, participants data analyzed simultaneously for rescue and extension period and reported collectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=5-point reduction: Week 28 | 100.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=5-point reduction: Week 4 | 45.5 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=5-point reduction: Week 8 | 60.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=5-point reduction: Week 12 | 50.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=5-point reduction: Week 14 | 25.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=5-point reduction: Week 16 | 70.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=5-point reduction: Week 20 | 77.8 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=5-point reduction: Week 24 | 62.5 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=5-point reduction: Week 2 | 25.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=5-point reduction: Week 32 | 50.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=5-point reduction: Week 36 | 75.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=5-point reduction: Week 40 | 100.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=5-point reduction: Week 44 | 100.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=5-point reduction: Week 48 | 100.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=5-point reduction: Week 52 | 100.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=8-point reduction: Week 2 | 16.7 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=8-point reduction: Week 4 | 27.3 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=8-point reduction: Week 8 | 40.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=8-point reduction: Week 12 | 40.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=8-point reduction: Week 14 | 25.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=8-point reduction: Week 16 | 60.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=8-point reduction: Week 20 | 55.6 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=8-point reduction: Week 24 | 50.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=8-point reduction: Week 28 | 100.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=8-point reduction: Week 32 | 50.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=8-point reduction: Week 36 | 75.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=8-point reduction: Week 40 | 100.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=8-point reduction: Week 44 | 100.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=8-point reduction: Week 48 | 100.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=8-point reduction: Week 52 | 66.7 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=5-point reduction: Week 56 | 100.0 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=8-point reduction: Week 14 | 16.7 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=5-point reduction: Week 60 | 100.0 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=5-point reduction: Week 64 | 100.0 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=8-point reduction: Week 48 | 75.0 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=8-point reduction: Week 2 | 15.4 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=8-point reduction: Week 32 | 66.7 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=5-point reduction: Week 2 | 38.5 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=8-point reduction: Week 4 | 30.8 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=5-point reduction: Week 4 | 38.5 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=8-point reduction: Week 64 | 100.0 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=5-point reduction: Week 8 | 53.8 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=8-point reduction: Week 8 | 30.8 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=5-point reduction: Week 12 | 53.8 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=8-point reduction: Week 36 | 33.3 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=5-point reduction: Week 14 | 50.0 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=8-point reduction: Week 12 | 30.8 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=5-point reduction: Week 16 | 60.0 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=8-point reduction: Week 52 | 66.7 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=5-point reduction: Week 20 | 75.0 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=8-point reduction: Week 40 | 50.0 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=5-point reduction: Week 24 | 71.4 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=8-point reduction: Week 16 | 40.0 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=5-point reduction: Week 28 | 85.7 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=8-point reduction: Week 56 | 100.0 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=5-point reduction: Week 32 | 100.0 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=8-point reduction: Week 20 | 62.5 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=5-point reduction: Week 36 | 83.3 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=8-point reduction: Week 44 | 60.0 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=5-point reduction: Week 40 | 50.0 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=8-point reduction: Week 24 | 57.1 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=5-point reduction: Week 44 | 60.0 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=8-point reduction: Week 60 | 50.0 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=5-point reduction: Week 48 | 75.0 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=8-point reduction: Week 28 | 57.1 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With at Least 5-point and 8-point Reduction From Baseline in Patient Reported Outcome 2 (PRO2) | >=5-point reduction: Week 52 | 66.7 percentage of participants |
Secondary
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.
Time frame: At Weeks 2, 4, 8, 12, 14, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60 and 64
Population: FAS was used for analysis. Here, number analyzed n= participants who were evaluable for outcome measure at given time points. As planned, combined data for all the periods (remission-induction, rescue and extension periods) was collected and reported in outcome measure due to same dosing of E6011. From Week 14-24, participants data analyzed simultaneously for rescue and extension period and reported collectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| E6011 10 mg/kg | Percentage of Participants With Below 150 CDAI Points | CDAI <150 points: Week 4 | 0.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With Below 150 CDAI Points | CDAI <150 points: Week 32 | 50.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With Below 150 CDAI Points | CDAI <150 points: Week 2 | 0.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With Below 150 CDAI Points | CDAI <150 points: Week 36 | 25.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With Below 150 CDAI Points | CDAI <150 points: Week 16 | 20.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With Below 150 CDAI Points | CDAI <150 points: Week 40 | 66.7 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With Below 150 CDAI Points | CDAI <150 points: Week 8 | 20.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With Below 150 CDAI Points | CDAI <150 points: Week 44 | 33.3 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With Below 150 CDAI Points | CDAI <150 points: Week 20 | 11.1 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With Below 150 CDAI Points | CDAI <150 points: Week 48 | 0.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With Below 150 CDAI Points | CDAI <150 points: Week 14 | 0.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With Below 150 CDAI Points | CDAI <150 points: Week 52 | 33.3 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With Below 150 CDAI Points | CDAI <150 points: Week 24 | 12.5 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With Below 150 CDAI Points | CDAI <150 points: Week 12 | 10.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With Below 150 CDAI Points | CDAI <150 points: Week 28 | 100.0 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With Below 150 CDAI Points | CDAI <150 points: Week 52 | 66.7 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With Below 150 CDAI Points | CDAI <150 points: Week 60 | 50.0 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With Below 150 CDAI Points | CDAI <150 points: Week 56 | 100.0 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With Below 150 CDAI Points | CDAI <150 points: Week 64 | 100.0 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With Below 150 CDAI Points | CDAI <150 points: Week 2 | 7.7 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With Below 150 CDAI Points | CDAI <150 points: Week 4 | 15.4 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With Below 150 CDAI Points | CDAI <150 points: Week 8 | 30.8 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With Below 150 CDAI Points | CDAI <150 points: Week 12 | 15.4 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With Below 150 CDAI Points | CDAI <150 points: Week 14 | 16.7 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With Below 150 CDAI Points | CDAI <150 points: Week 16 | 30.0 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With Below 150 CDAI Points | CDAI <150 points: Week 20 | 37.5 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With Below 150 CDAI Points | CDAI <150 points: Week 24 | 42.9 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With Below 150 CDAI Points | CDAI <150 points: Week 28 | 42.9 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With Below 150 CDAI Points | CDAI <150 points: Week 32 | 83.3 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With Below 150 CDAI Points | CDAI <150 points: Week 36 | 33.3 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With Below 150 CDAI Points | CDAI <150 points: Week 40 | 50.0 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With Below 150 CDAI Points | CDAI <150 points: Week 44 | 60.0 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With Below 150 CDAI Points | CDAI <150 points: Week 48 | 50.0 percentage of participants |
Secondary
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
Population: FAS was used for analysis. Here, n = participants who were evaluable for outcome measure at given time points. As planned, combined data for all the periods (remission-induction, rescue and extension periods) was collected and reported in outcome measure due to same dosing of E6011. From Week 14-24, participants data analyzed simultaneously for rescue and extension period and reported collectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| E6011 10 mg/kg | Percentage of Participants With Below 8 Points in PRO2 | PRO2 <8 points: Week 2 | 8.3 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With Below 8 Points in PRO2 | PRO2 <8 points: Week 4 | 9.1 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With Below 8 Points in PRO2 | PRO2 <8 points: Week 8 | 20.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With Below 8 Points in PRO2 | PRO2 <8 points: Week 12 | 10.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With Below 8 Points in PRO2 | PRO2 <8 points: Week 14 | 0.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With Below 8 Points in PRO2 | PRO2 <8 points: Week 16 | 10.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With Below 8 Points in PRO2 | PRO2 <8 points: Week 20 | 0.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With Below 8 Points in PRO2 | PRO2 <8 points: Week 24 | 12.5 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With Below 8 Points in PRO2 | PRO2 <8 points: Week 28 | 25.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With Below 8 Points in PRO2 | PRO2 <8 points: Week 32 | 25.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With Below 8 Points in PRO2 | PRO2 <8 points: Week 36 | 0.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With Below 8 Points in PRO2 | PRO2 <8 points: Week 40 | 33.3 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With Below 8 Points in PRO2 | PRO2 <8 points: Week 44 | 0.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With Below 8 Points in PRO2 | PRO2 <8 points: Week 48 | 0.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With Below 8 Points in PRO2 | PRO2 <8 points: Week 52 | 33.3 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With Below 8 Points in PRO2 | PRO2 <8 points: Week 24 | 28.6 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With Below 8 Points in PRO2 | PRO2 <8 points: Week 60 | 50.0 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With Below 8 Points in PRO2 | PRO2 <8 points: Week 28 | 14.3 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With Below 8 Points in PRO2 | PRO2 <8 points: Week 48 | 50.0 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With Below 8 Points in PRO2 | PRO2 <8 points: Week 2 | 7.7 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With Below 8 Points in PRO2 | PRO2 <8 points: Week 32 | 33.3 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With Below 8 Points in PRO2 | PRO2 <8 points: Week 4 | 7.7 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With Below 8 Points in PRO2 | PRO2 <8 points: Week 64 | 100.0 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With Below 8 Points in PRO2 | PRO2 <8 points: Week 8 | 23.1 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With Below 8 Points in PRO2 | PRO2 <8 points: Week 36 | 16.7 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With Below 8 Points in PRO2 | PRO2 <8 points: Week 12 | 15.4 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With Below 8 Points in PRO2 | PRO2 <8 points: Week 52 | 66.7 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With Below 8 Points in PRO2 | PRO2 <8 points: Week 14 | 16.7 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With Below 8 Points in PRO2 | PRO2 <8 points: Week 40 | 25.0 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With Below 8 Points in PRO2 | PRO2 <8 points: Week 16 | 30.0 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With Below 8 Points in PRO2 | PRO2 <8 points: Week 56 | 100.0 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With Below 8 Points in PRO2 | PRO2 <8 points: Week 20 | 37.5 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With Below 8 Points in PRO2 | PRO2 <8 points: Week 44 | 40.0 percentage of participants |
Secondary
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
Population: FAS was used for analysis. Here number analyzed ('n') = participants who were evaluable for outcome measure at given time points. As planned, combined data for all the periods (remission-induction, rescue and extension periods) was collected and reported in outcome measure due to same dosing of E6011. From Week 14-24, participants data analyzed simultaneously for rescue and extension period and reported collectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR100: Week 28 | 100.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR70: Week 4 | 45.5 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR70: Week 8 | 50.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR70: Week 12 | 50.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR70: Week 14 | 25.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR70: Week 16 | 70.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR70: Week 20 | 66.7 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR70: Week 24 | 62.5 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR70: Week 28 | 100.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR70: Week 32 | 50.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR70: Week 36 | 100.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR70: Week 40 | 100.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR70: Week 44 | 100.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR70: Week 48 | 66.7 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR70: Week 52 | 66.7 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR100: Week 2 | 16.7 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR100: Week 4 | 18.2 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR100: Week 8 | 30.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR100: Week 12 | 40.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR100: Week 14 | 25.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR100: Week 16 | 70.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR100: Week 20 | 55.6 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR100: Week 24 | 50.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR70: Week 2 | 16.7 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR100: Week 32 | 50.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR100: Week 36 | 75.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR100: Week 40 | 100.0 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR100: Week 44 | 66.7 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR100: Week 48 | 66.7 percentage of participants |
| E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR100: Week 52 | 66.7 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR70: Week 56 | 100.0 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR70: Week 60 | 100.0 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR70: Week 64 | 100.0 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR100: Week 48 | 75.0 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR100: Week 2 | 15.4 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR100: Week 32 | 83.3 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR100: Week 4 | 23.1 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR70: Week 2 | 23.1 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR100: Week 64 | 100.0 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR70: Week 4 | 23.1 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR100: Week 8 | 30.8 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR70: Week 8 | 38.5 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR100: Week 36 | 50.0 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR70: Week 12 | 46.2 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR100: Week 12 | 23.1 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR70: Week 14 | 33.3 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR100: Week 52 | 66.7 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR70: Week 16 | 60.0 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR100: Week 14 | 33.3 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR70: Week 20 | 62.5 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR100: Week 40 | 75.0 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR70: Week 24 | 71.4 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR100: Week 16 | 50.0 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR70: Week 28 | 85.7 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR100: Week 56 | 100.0 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR70: Week 32 | 83.3 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR100: Week 20 | 50.0 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR70: Week 36 | 83.3 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR100: Week 44 | 80.0 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR70: Week 40 | 75.0 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR100: Week 24 | 57.1 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR70: Week 44 | 80.0 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR100: Week 60 | 50.0 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR70: Week 48 | 100.0 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR100: Week 28 | 71.4 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With CR70 and CR100 | CR70: Week 52 | 66.7 percentage of participants |
Secondary
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
Population: The FAS included participants to whom the IMP has been administered after randomization, and who had 1 or more evaluable, post-IMP administration primary efficacy endpoint (that is, to have an evaluable (CDAI) value at baseline and any other post baseline).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| E6011 10 mg/kg | Percentage of Participants With Less Than or Equal to (<=) 2 (Endoscopic Remission) SES-CD Score at Week 12 | 8.3 percentage of participants |
| Placebo Then E6011 10 mg/kg | Percentage of Participants With Less Than or Equal to (<=) 2 (Endoscopic Remission) SES-CD Score at Week 12 | 0.0 percentage of participants |
95% CI: [-7.3, 24]
Secondary
Percent 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
Population: FAS was used for analysis. Here n = participants who were evaluable for outcome measure at given time points. As planned, combined data for all the periods (remission-induction, rescue and extension periods) was collected and reported in outcome measure due to same dosing of E6011. From Week 14-24, participants data analyzed simultaneously for rescue and extension period and reported collectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| E6011 10 mg/kg | Percent Change From Baseline in CDAI Score | Percent Change at Week 2 | -8.9 percent change | Standard Deviation 24.6 |
| E6011 10 mg/kg | Percent Change From Baseline in CDAI Score | Percent Change at Week 4 | -16.0 percent change | Standard Deviation 26.1 |
| E6011 10 mg/kg | Percent Change From Baseline in CDAI Score | Percent Change at Week 8 | -25.8 percent change | Standard Deviation 27.7 |
| E6011 10 mg/kg | Percent Change From Baseline in CDAI Score | Percent Change at Week 12 | -25.3 percent change | Standard Deviation 27.1 |
| E6011 10 mg/kg | Percent Change From Baseline in CDAI Score | Percent Change at Week 14 | -8.3 percent change | Standard Deviation 28.4 |
| E6011 10 mg/kg | Percent Change From Baseline in CDAI Score | Percent Change at Week 16 | -29.3 percent change | Standard Deviation 23.6 |
| E6011 10 mg/kg | Percent Change From Baseline in CDAI Score | Percent Change at Week 20 | -34.5 percent change | Standard Deviation 17.5 |
| E6011 10 mg/kg | Percent Change From Baseline in CDAI Score | Percent Change at Week 24 | -34.8 percent change | Standard Deviation 25.3 |
| E6011 10 mg/kg | Percent Change From Baseline in CDAI Score | Percent Change at Week 28 | -53.6 percent change | Standard Deviation 3.4 |
| E6011 10 mg/kg | Percent Change From Baseline in CDAI Score | Percent Change at Week 32 | -31.4 percent change | Standard Deviation 29.3 |
| E6011 10 mg/kg | Percent Change From Baseline in CDAI Score | Percent Change at Week 36 | -43.3 percent change | Standard Deviation 10.3 |
| E6011 10 mg/kg | Percent Change From Baseline in CDAI Score | Percent Change at Week 40 | -53.9 percent change | Standard Deviation 15.7 |
| E6011 10 mg/kg | Percent Change From Baseline in CDAI Score | Percent Change at Week 44 | -45.7 percent change | Standard Deviation 23.1 |
| E6011 10 mg/kg | Percent Change From Baseline in CDAI Score | Percent Change at Week 48 | -39.6 percent change | Standard Deviation 17.8 |
| E6011 10 mg/kg | Percent Change From Baseline in CDAI Score | Percent Change at Week 52 | -33.0 percent change | Standard Deviation 32.4 |
| Placebo Then E6011 10 mg/kg | Percent Change From Baseline in CDAI Score | Percent Change at Week 24 | -32.6 percent change | Standard Deviation 44.1 |
| Placebo Then E6011 10 mg/kg | Percent Change From Baseline in CDAI Score | Percent Change at Week 60 | -51.9 percent change | Standard Deviation 37.1 |
| Placebo Then E6011 10 mg/kg | Percent Change From Baseline in CDAI Score | Percent Change at Week 28 | -48.3 percent change | Standard Deviation 26.2 |
| Placebo Then E6011 10 mg/kg | Percent Change From Baseline in CDAI Score | Percent Change at Week 48 | -63.7 percent change | Standard Deviation 25.5 |
| Placebo Then E6011 10 mg/kg | Percent Change From Baseline in CDAI Score | Percent Change at Week 2 | -16.7 percent change | Standard Deviation 21.1 |
| Placebo Then E6011 10 mg/kg | Percent Change From Baseline in CDAI Score | Percent Change at Week 32 | -60.1 percent change | Standard Deviation 28.3 |
| Placebo Then E6011 10 mg/kg | Percent Change From Baseline in CDAI Score | Percent Change at Week 4 | -20.6 percent change | Standard Deviation 26.6 |
| Placebo Then E6011 10 mg/kg | Percent Change From Baseline in CDAI Score | Percent Change at Week 64 | -87.6 percent change | — |
| Placebo Then E6011 10 mg/kg | Percent Change From Baseline in CDAI Score | Percent Change at Week 8 | -23.1 percent change | Standard Deviation 37.1 |
| Placebo Then E6011 10 mg/kg | Percent Change From Baseline in CDAI Score | Percent Change at Week 36 | -43.5 percent change | Standard Deviation 30.2 |
| Placebo Then E6011 10 mg/kg | Percent Change From Baseline in CDAI Score | Percent Change at Week 12 | -21.8 percent change | Standard Deviation 33.9 |
| Placebo Then E6011 10 mg/kg | Percent Change From Baseline in CDAI Score | Percent Change at Week 52 | -53.8 percent change | Standard Deviation 48.2 |
| Placebo Then E6011 10 mg/kg | Percent Change From Baseline in CDAI Score | Percent Change at Week 14 | -9.3 percent change | Standard Deviation 36.6 |
| Placebo Then E6011 10 mg/kg | Percent Change From Baseline in CDAI Score | Percent Change at Week 40 | -50.2 percent change | Standard Deviation 23.7 |
| Placebo Then E6011 10 mg/kg | Percent Change From Baseline in CDAI Score | Percent Change at Week 16 | -27.5 percent change | Standard Deviation 37 |
| Placebo Then E6011 10 mg/kg | Percent Change From Baseline in CDAI Score | Percent Change at Week 56 | -77.0 percent change | — |
| Placebo Then E6011 10 mg/kg | Percent Change From Baseline in CDAI Score | Percent Change at Week 20 | -36.6 percent change | Standard Deviation 45.4 |
| Placebo Then E6011 10 mg/kg | Percent Change From Baseline in CDAI Score | Percent Change at Week 44 | -56.8 percent change | Standard Deviation 27.1 |
Secondary
Percent Change From Baseline 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
Population: FAS was used for analysis. Here n = participants who were evaluable for outcome measure at given time points. As planned, combined data for all the periods (remission-induction, rescue and extension periods) was collected and reported in outcome measure due to same dosing of E6011. From Week 14-24, participants data analyzed simultaneously for rescue and extension period and reported collectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| E6011 10 mg/kg | Percent Change From Baseline in PRO2 | Percent Change at Week 32 | -25.1 percent change | Standard Deviation 32.7 |
| E6011 10 mg/kg | Percent Change From Baseline in PRO2 | Percent Change at Week 8 | -30.1 percent change | Standard Deviation 33 |
| E6011 10 mg/kg | Percent Change From Baseline in PRO2 | Percent Change at Week 36 | -37.1 percent change | Standard Deviation 25.5 |
| E6011 10 mg/kg | Percent Change From Baseline in PRO2 | Percent Change at Week 16 | -36.8 percent change | Standard Deviation 25 |
| E6011 10 mg/kg | Percent Change From Baseline in PRO2 | Percent Change at Week 40 | -56.4 percent change | Standard Deviation 14.3 |
| E6011 10 mg/kg | Percent Change From Baseline in PRO2 | Percent Change at Week 4 | -23.0 percent change | Standard Deviation 29.8 |
| E6011 10 mg/kg | Percent Change From Baseline in PRO2 | Percent Change at Week 44 | -46.9 percent change | Standard Deviation 9.1 |
| E6011 10 mg/kg | Percent Change From Baseline in PRO2 | Percent Change at Week 20 | -36.2 percent change | Standard Deviation 16.8 |
| E6011 10 mg/kg | Percent Change From Baseline in PRO2 | Percent Change at Week 48 | -37.3 percent change | Standard Deviation 7.2 |
| E6011 10 mg/kg | Percent Change From Baseline in PRO2 | Percent Change at Week 12 | -29.4 percent change | Standard Deviation 28 |
| E6011 10 mg/kg | Percent Change From Baseline in PRO2 | Percent Change at Week 52 | -38.4 percent change | Standard Deviation 22.2 |
| E6011 10 mg/kg | Percent Change From Baseline in PRO2 | Percent Change at Week 24 | -30.0 percent change | Standard Deviation 28 |
| E6011 10 mg/kg | Percent Change From Baseline in PRO2 | Percent Change at Week 2 | -13.5 percent change | Standard Deviation 31.3 |
| E6011 10 mg/kg | Percent Change From Baseline in PRO2 | Percent Change at Week 28 | -47.7 percent change | Standard Deviation 9.2 |
| E6011 10 mg/kg | Percent Change From Baseline in PRO2 | Percent Change at Week 14 | -13.4 percent change | Standard Deviation 28.6 |
| Placebo Then E6011 10 mg/kg | Percent Change From Baseline in PRO2 | Percent Change at Week 56 | -81.3 percent change | — |
| Placebo Then E6011 10 mg/kg | Percent Change From Baseline in PRO2 | Percent Change at Week 60 | -59.4 percent change | Standard Deviation 39.8 |
| Placebo Then E6011 10 mg/kg | Percent Change From Baseline in PRO2 | Percent Change at Week 2 | -20.9 percent change | Standard Deviation 20 |
| Placebo Then E6011 10 mg/kg | Percent Change From Baseline in PRO2 | Percent Change at Week 64 | -93.8 percent change | — |
| Placebo Then E6011 10 mg/kg | Percent Change From Baseline in PRO2 | Percent Change at Week 4 | -22.9 percent change | Standard Deviation 28.4 |
| Placebo Then E6011 10 mg/kg | Percent Change From Baseline in PRO2 | Percent Change at Week 8 | -29.2 percent change | Standard Deviation 34.6 |
| Placebo Then E6011 10 mg/kg | Percent Change From Baseline in PRO2 | Percent Change at Week 12 | -25.8 percent change | Standard Deviation 31 |
| Placebo Then E6011 10 mg/kg | Percent Change From Baseline in PRO2 | Percent Change at Week 14 | -17.6 percent change | Standard Deviation 32.7 |
| Placebo Then E6011 10 mg/kg | Percent Change From Baseline in PRO2 | Percent Change at Week 16 | -27.9 percent change | Standard Deviation 34.4 |
| Placebo Then E6011 10 mg/kg | Percent Change From Baseline in PRO2 | Percent Change at Week 20 | -37.6 percent change | Standard Deviation 46.7 |
| Placebo Then E6011 10 mg/kg | Percent Change From Baseline in PRO2 | Percent Change at Week 24 | -35.9 percent change | Standard Deviation 41.1 |
| Placebo Then E6011 10 mg/kg | Percent Change From Baseline in PRO2 | Percent Change at Week 28 | -46.2 percent change | Standard Deviation 23.7 |
| Placebo Then E6011 10 mg/kg | Percent Change From Baseline in PRO2 | Percent Change at Week 32 | -58.3 percent change | Standard Deviation 30.3 |
| Placebo Then E6011 10 mg/kg | Percent Change From Baseline in PRO2 | Percent Change at Week 36 | -42.9 percent change | Standard Deviation 24.6 |
| Placebo Then E6011 10 mg/kg | Percent Change From Baseline in PRO2 | Percent Change at Week 40 | -31.2 percent change | Standard Deviation 32.6 |
| Placebo Then E6011 10 mg/kg | Percent Change From Baseline in PRO2 | Percent Change at Week 44 | -45.3 percent change | Standard Deviation 32.5 |
| Placebo Then E6011 10 mg/kg | Percent Change From Baseline in PRO2 | Percent Change at Week 48 | -57.2 percent change | Standard Deviation 26.7 |
| Placebo Then E6011 10 mg/kg | Percent Change From Baseline in PRO2 | Percent Change at Week 52 | -56.1 percent change | Standard Deviation 34.6 |
Secondary
Percent 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
Population: FAS was used for analysis. Here overall number of participants analyzed ('N') = participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| E6011 10 mg/kg | Percent Change From Baseline in SES-CD Score at Week 12 | -0.3 percent change | Standard Deviation 45.6 |
| Placebo Then E6011 10 mg/kg | Percent Change From Baseline in SES-CD Score at Week 12 | -19.2 percent change | Standard Deviation 33.2 |
Secondary
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
Population: FAS was used for analysis. Here, N = participants who were evaluable for this outcome measure. As planned, combined data for all the periods (remission-induction, rescue, extension and post observation periods) was collected and reported in outcome measure due to same dosing of E6011.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| E6011 10 mg/kg | Percent Change From Baseline in Steroid Dosage in Participants Concomitantly Using Adrenocorticosteroids up to Week 64 | 0 percent change | Standard Deviation 0 |
| Placebo Then E6011 10 mg/kg | Percent Change From Baseline in Steroid Dosage in Participants Concomitantly Using Adrenocorticosteroids up to Week 64 | 0 percent change | Standard Deviation 0 |