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

Crohn's Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03733314
• Other study ID #: E6011-ET2
• Secondary ID: 2018-002109-7018
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: April 25, 2019
• Est. completion date: April 1, 2024

Study information

• Verified date: January 2024
• Source: Eisai Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 25
• Est. completion date: April 1, 2024
• Est. primary completion date: March 16, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 64 Years

Eligibility

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.

Related Conditions & MeSH terms

• Crohn Disease
• Crohn's Disease

Intervention

Drug:
• E6011
E6011, infusion, intravenously.
• Placebo
Placebo, infusion, intravenously.

Locations

Country	Name	City	State
Czechia	49, CCR Ostrava, s.r.o	Ostrava
Hungary	15, University of Debrecen Clinical Centre	Debrecen
Hungary	19, Semmelweis university	Gyor
Japan	10	Abiko	Chiba
Japan	36	Akita
Japan	38	Asahikawa	Hokkaido
Japan	2	Bunkyo	Tokyo
Japan	25	Fukuoka
Japan	35	Fukuoka
Japan	11	Gifu
Japan	33	Hachioji	Tokyo
Japan	51	Hamamatsu	Shizuoka
Japan	42	Hirakata	Osaka
Japan	52	Isehara	Kanagawa
Japan	5	Kagoshima
Japan	32	Kanazawa	Ishikawa
Japan	40	Kanazawa
Japan	29	Kasamatsu	Gifu
Japan	31	Kashiwa	Chiba
Japan	27	Kitakyushu	Fukuoka
Japan	39	Kitakyushu	Fukuoka
Japan	37	Kobe	Hyogo
Japan	34	Kodaira	Tokyo
Japan	41	Kure	Hiroshima
Japan	3	Minato	Tokyo
Japan	6	Mitaka	Tokyo
Japan	4	Nagoya	Aichi
Japan	7	Nishinomiya	Hyogo
Japan	30	Oiso	Kanagawa
Japan	24	Osaka
Japan	26	Sapporo	Hokkaido
Japan	43	Shinagawa-Ku	Tokyo
Japan	1	Shinjuku	Tokyo
Japan	50	Shuntougun	Shizuoka
Japan	8	Takamatsu	Kagawa
Japan	17	Toyota	Aichi
Japan	28	Urasoe	Okinawa
Poland	21, Vitamed Galaj i Cichomski sp.j.	Bydgoszcz
Poland	22, Vita Longa	Katowice
Poland	20, Clinical Research Center sp. z o.o., Medic-R Sp. k.	Poznan
Poland	23, Centrum Badan Klinicznych - Osrodek Badan Wczesnej Fazy	Wroclaw
Russian Federation	45, Federal Siberian Research and Clinical Center	Krasnoyarsk
Russian Federation	44, LLC, Novosibirskiy Gastrocenter	Novosibirsk
Russian Federation	46, Pyatigorsk City Clinical Hospital	Pyatigorsk
Russian Federation	48, LLC Clinic, UZI 4D	Pyatigorsk
Russian Federation	47, City Hospital of Saint Martyr Elizaveth	Saint Petersburg

Sponsors (1)

Lead Sponsor	Collaborator
EA Pharma Co., Ltd.

Countries where clinical trial is conducted

Czechia,  Hungary,  Japan,  Poland,  Russian Federation, 

Outcome

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