|E.1 Medical condition or disease under investigation
|Medical condition(s) being investigated
|Medical condition in easily understood language
|Presence of a type of inflammatory bowel disease, called Crohn’s disease
|Diseases [C] - Digestive System Diseases [C06]
|E.1.2 Medical condition or disease under investigation
|System Organ Class
|10017947 - Gastrointestinal disorders
|Condition being studied is a rare disease
|E.2 Objective of the trial
|Main objective of the trial
|To examine the efficacy and safety of E6011 at 12 weeks after administration by means of double-blind placebo-controlled trial
|Secondary objectives of the trial
|To examine the efficacy and safety of a long-term administration of E6011.
To evaluate the pharmacokinetics and immunogenicity of E6011.
|Trial contains a sub-study
|Principal inclusion criteria
|Subjects who meet all of the following criteria are eligible to participate in this clinical trial.
(1) Crohn’s disease patients aged 18 or over and under 65 on the date of consent.
(2) Patients 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.
(3) Patients with a baseline (at Week 0 before the start of IMP administration) disease severity ranging from moderate to severe. CDAI score between 220 and 450, and a PRO2 score between 14 and 34.
(4) Patients with a Simple Endoscopic Score for Crohn’s Disease (SES-CD) ≥ 7 (or for patients 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.
(5) Patients who received adrenocorticosteroids or immunomodulators in the past, but showed no therapeutic response (insufficient response) or the drugs were not tolerated (intolerance). Alternatively, patients who cannot taper adrenocorticosteroids (dependence). Alternatively, patients who showed no therapeutic response after administering biologic(s) (primary nonresponse), patients who initially showed therapeutic response but it lessened or disappeared afterwards (secondary nonresponse), or patients who did not tolerate the drug (intolerance). (Detailed criteria are described in Attachment 7 and Attachment 8).
(6) If the patients are taking 1,200 kcal/day or less enteral nutrition, the dosage and administration have not changed for at least 4 weeks prior to the start of the IMP administration.
(7) If the patients 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.
(8) If the patients are taking under 30 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.
(9) If the patients 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.
(10) Patients who have received a sufficient explanation about the compliance rules of this clinical trial, who are willing to comply with them, and who are able to do so.
(11) Patients who voluntarily gave a written consent to participate in this clinical trial.
|Principal exclusion criteria
|Patients diagnosed with ulcerative colitis or indeterminate colitis
Patients diagnosed with gastrointestinal epithelial dysplasia
Patients who have an abscess or are suspected to have one
Patients with an artificial anus, ileo-anal pouch or fistula
Patients with symptomatic or high-grade gastrointestinal stenosis
Patients who, after undergoing small bowel resection, have been diagnosed with a short bowel syndrome, which makes maintaining caloric intake difficult
Patients who have newly started seton drainage treatment within 12 weeks prior to the start of the IMP
Patients who have undergone bowel resection or a gastrointestinal surgery within 24 weeks prior to the start of the IMP administration
Patients who tested positive for C. difficile toxin test in the screening
Patients who tested positive for HIV, hepatitis B surface antigen, hepatitis B surface antibody, hepatitis B core antibody, hepatitis B virus DNA, hepatitis C virus antibody, or human T cell leukemia virus type 1 antibody in the screening
Patients with positive or repeated indeterminate results on the TB test
Patients with findings showing a history of tuberculosis on a chest X-ray test in the screening period
Patients with findings of neurological symptoms such as motor impairment, cognitive disorder, language disorder or dysphagia in the evaluations during the screening period
Patients with a WBC count of less than 3,000/μL or blood CD4+ cell count under 200/μL in the screening tests
Patients with a medical history of clinically significant vasculitis
Acute myocardial infarction, unstable angina pectoris, cerebral infarction, and symptomatic cerebral haemorrhage patients
Patients whose AST or ALT was more than three times the UNL in the screening period tests or patients whose serum creatinine level was more than 1.5 times the UNL in the screening tests
Patients with a QTcF exceeding 450 ms repeatedly in standard 12-lead ECG tests in the screening period tests
Patients who have undergone cytoapheresis (granulocytapheresis) within 2 weeks prior to the start of the IMP
Hospitalisation within 4 weeks prior to the start of IMP, intravenous treatment of antibiotics, antiviral drugs within 4 weeks prior to the start of IMP or oral treatment of antibiotics, antiviral drugs within 2 weeks prior to the start of IMP. COVID-19: patients required hospitalization within 4 weeks prior to the start of the IMP, any intravenous treatment within 4 weeks prior to the start of the IMP or any oral treatment within 2 weeks prior to the start of IMP
Patients who received total parenteral nutrition, peripheral parenteral nutrition, or enteral nutrition exceeding 1200 kcal/day within 4 weeks prior to the start of the IMP
Patients who received ≥30 mg/day of oral prednisolone (or an equivalent adrenocorticosteroid), adrenocorticosteroid injection, enema or suppository within 4 weeks prior to the start of the IMP
Patients who received cyclosporine, mycophenolate mofetil, or tacrolimus within 8 weeks prior to the start of the IMP
Patients who received adalimumab, infliximab, certolizumab pegol, vedolizumab or ustekinumab within 8 weeks prior to the start of the IMP
Patients vaccinated with live vaccines within 12 weeks prior to the start of the IMP
Patients who received an immunoglobulin preparation or a blood product within 24 weeks prior to the start of the IMP administration
Patients who have received natalizumab or E6011 in the past
Patients with a history of a malignant tumour, lymphoma, leukemia, or lymphoproliferative disorders, or with complications thereof
Patients with immunodeficiency or a history of HIV infection
Patients with a history of severe allergy
Patients currently taking part in another clinical trial (including the post-observation period), or patients who were participating in another trial using an IMP or investigational medical device within 28 days (or within five times the length of the half-life period of the IMP, whichever is longer) prior to giving consent
Patients who received a faecal microbiota transplant, mesenchymal stem cell, etc. within 24 weeks prior to giving consent
Female patients of childbearing potential who had a positive result on the pregnancy test at screening or baseline, as well as lactating patients
Female patients of childbearing potential who:
have not been on a highly effective method of contraception within 28 days prior to the start of IMP administration
Potential male patients with female partners of childbearing potential:
that have not undergone proper vasectomy
patients whose female partner is pregnant and do not agree to use latex or synthetic condoms during the clinical trial and for 70 days after the last administration of the IMP
the patients must not donate sperm during the clinical trial and for 70 days after the last administration of the IMP
Patients who were judged to be unsuitable for participation in this clinical trial by the investigator
|E.5 End points
|Primary end point(s)
|CR100 (CDAI reductions of at least 100 points) response rate
|Timepoint(s) of evaluation of this end point
|Secondary end point(s)
|• CR70 response rate, CR100 response rate (excluding Week 12) and CDAI remission rate (proportion of subjects with below 150 points) at each evaluation time
•proportion of subjects with at least 5-point reduction in PRO2 from baseline (PRO2-CR5 response rate), proportion of subjects with at least 8-point reduction from baseline (PRO2-CR8 response rate), and proportion of subjects with below 8 points (PRO2-resmission rate) at each evaluation time
• Proportion of subjects with at least 50% improvement in SES-CD score from prior to IMP administration (endoscopic response rate) and proportion of subjects with 2 or less in SES-CD score (endoscopic remission rate) at Week 12
• Change and percent change in CDAI score from baseline at each evaluation time
• Change and percent change in PRO2 from baseline at each evaluation time
• Change and percent change in SES-CD score from baseline at Week 12
• In subjects who were concomintantly taking adrenocorticosteroid, proportion of subjects who achieved steroid-free maintenance (steroid-free remission rate, steroid-free improvement rate) through steroid dose reduction and clinical remission (CDAI remission or PRO2 remission) or clinical improvement (CR70 response, CR100 response, PRO2-CR5 response or PRO2-CR8 response)
• In subjects who were concomintantly taking adrenocorticosteroid, dosage, change and percent change of adrenocorticosteroid from baseline
|Timepoint(s) of evaluation of this end point
|Week2, Week4, Week8, Week12, Responders: Week16, Week 20, Week24, Week28, Week32, Week36, Week40, Week44, Week48, Week 52, Non-responders: Week14, Week16, Week20, Week24, Week28, Week32, Week36, Week40, Week44, Week48, Week 52, Week56, Week60, Week64, or at discontinuation in any period
|E.6 and E.7 Scope of the trial
|Scope of the trial
|Trial type and phase
|Human pharmacology (Phase I)
|First administration to humans
|Other trial type description
|Therapeutic exploratory (Phase II)
|Therapeutic confirmatory (Phase III)
|Therapeutic use (Phase IV)
|E.8 Design of the trial
| Comparator of controlled trial
|Other medicinal product(s)
|Number of treatment arms in the trial
The trial involves single site in the Member State concerned
| The trial involves multiple sites in the Member State concerned
|Number of sites anticipated in Member State concerned
|The trial involves multiple Member States
|Number of sites anticipated in the EEA
|E.8.6 Trial involving sites outside the EEA
|Trial being conducted both within and outside the EEA
|Trial being conducted completely outside of the EEA
|If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
|Trial has a data monitoring committee
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|E.8.9 Initial estimate of the duration of the trial
|In the Member State concerned years
|In the Member State concerned months
|In the Member State concerned days
|In all countries concerned by the trial years
|In all countries concerned by the trial months