E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
This is a phase 3, multicenter, randomized, double-blinded, placebo-controlled, parallel-group study to examine the efficacy, safety, and pharmacokinetics of intravenous Vedolizumab (300 mg) infusion in induction and maintenance therapy in Japanese patients with moderately or severely active Crohn's disease. |
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E.1.1.1 | Medical condition in easily understood language |
Moderately or severely active Crohn's disease. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate efficacy of MLN0002 in induction and maintenance therapy in Japanese subjects with moderately or severely active Crohn's disease. |
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E.2.2 | Secondary objectives of the trial |
To evaluate safety of MLN0002 in induction and maintenance therapy in Japanese subjects with moderately or severely active Crohn's disease. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients aged 15 to 80 years (inclusive) at the time of consent 2. Patients with a diagnosis of small-intestinal, large-intestinal,or small-/large-intestinal Crohn's disease established based on the Revised Diagnostic Criteria for Crohn’s disease issued by Research Group for Intractable Inflammatory Bowel Disease Designated as Specified Disease by the Ministry of Health, Labor and Welfare of Japan (2012) at least 3 months before the start of administration of study drug 3. Patients with baseline Crohn's Disease Activity Index (CDAI) score of 220 to 450(inclusive) and meeting at least one of the followings:
・C-reactive protein (CRP) at screening test is above 0.30 mg/dL ・Patients with irregular or semicircular ulcers or multiple aphthae (10 or more) observed over an extensive area of the small or large intestine on endoscopy or imaging test within the 4 months before the start of administration of study drugs ・Patients with longitudinal ulcers or a cobblestone appearance observed in the small or large intestine on endoscopy or imaging test within 4 months before the start of administration of study drugs 4. In case of the patients who meet any of the following criteria; patients with ≥ 8-year history of extensive or limited colitis, patients aged ≥ 50 years, or patients with a first-degree family history of colon cancer, those whom the complication of colon cancer or dysplasia was ruled out by total colonoscopy at the start of study drug administration (Or the results from total colonoscopy performed within 1 year before giving consent are available) 5. Patients meeting the criteria for treatment failure below with at least one of the following agents received within previous 5 year period before giving consent ・Corticosteroids ・ Resistance ・ Dependence ・ Intolerance ・Immunomodulators (azathioprine, 6-mercaptopurine or methotrexate) ・ Refractory ・ Intolerance ・Anti-TNFα antibodies ・ Inadequate response ・Loss of response ・Intolerance |
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E.4 | Principal exclusion criteria |
1. Patients with an evidence of or suspected abdominal abscess 2. Patients with a history of subtotal or total colectomy 3. Patients who have had a resection of the small intestine in at least 3 locations or have a diagnosis of short bowel syndrome 4. Patients with ileostomy,colostomy,or internal fistula, or severe intestinal stenosis 5. Patients who started 5-aminosalicylic acid oral drug or probiotics treatment, antimicrobials to treat Crohn’s disease, or 30 mg/day or less of oral corticosteroids within 13 days before initiation of study drug administration. If these drugs were used within 14 days before initiation of study drug administration, the dosage must have been changed or their use discontinued within 13 days before the initiation of study drug administration 6. Patients who have received 5-aminosalicylic acid or corticosteroid enemas/suppositories, intravenous corticosteroid injections, or more than 30 mg/day of oral corticosteroids, medications for diarrhea-predominant irritable bowel syndrome, or Chinese herbal medicine for the treatment of Crohn’s disease (e.g., Daikenchuto) within 13 days before initiation of study drug administration 7. Patients who have received azathioprine, 6-mercaptopurine, or methotrexate within 27 days before initiation of study drug administration. However, this shall not apply to patients who have received these drugs for 83 or more days before initiation of the study drug administration and continued the steady dose administration of the drugs for 27 or more days before initiation of the study drug administration 8. Patients who have received cyclosporin, tacrolimus, tofacitinib or any study drugs for treatment of ulcerative colitis within 27 days before initiation of the study drug administration 9. Patients who have received adalimumab within 27 days before initiation of study drug administration or any biological drugs other than adalimumab within 55 days before initiation of study drug administration.Topical administration (such as intraocular implantation for treatment of age-related maculopacy) is allowed 10. Patients who have received any live vaccinations within 27 days before initiation of study drug administration 11. Patients who have undergone intestinal resection within 27 days before initiation of study drug administration or those anticipated to require intestinal resection during the study 12. Patients who have received leukocytapheresis or granulocyte apheresis within 27 days before initiation of the study drug administration 13. Patients who have received intravenous hyperalimentation or total enteral nutrition within the 20 days before initiation of the study drug administration. Or patients who are fasted 14. Patients who have received enteral nutrition at > 900 kcal/day or started enteral nutrition at <= 900 kcal/day within the 20 days before initiation of the study drug administration. Patients receiving 900 kcal/day or less of enteral nutrition for at least 21 days before initiation of the study drug administration whom these dosage was changed or the medications were discontinued within 20 days before initiation of the study drug administration 15. Patients with evidence of adenomatous colonic polyps that need to be removed at the start of study drug administration 16. Patients with a history or an an complication of dysplasia of the small or large intestine |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Induction phase: Crohn's Disease Activity Index (CDAI)-100 response at Week 10 - Maintenance Phase: Clinical remission at Week 60 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
- Induction phase: 10 weeks - Maintenance phase: 60 weeks |
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E.5.2 | Secondary end point(s) |
- Induction phase: Clinical remission at Week 10 - Induction phase: Changes in C-reactive protein (CRP) values - Maintenance Phase: Crohn's Disease Activity Index (CDAI)-100 response at Week 60 - Maintenance Phase: Durable clinical remission - Maintenance Phase: Corticosteroid-free clinical remission at Week 60 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Induction phase respectively: - Week 10 - From baseline to Week 10
Maintenance phase respectively: - Week 60 - From Week 14 to Week 60 - From baseline to 16 weeks after the last dose of study drug |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end-of-study examination performed at 16 weeks after the last dose in all subjects who received the study drug. In addition, the follow-up survey performed every 6 months from the last dose of the study drug up to 2 years or until the date of marketing approval of the study drug, whichever comes earlier. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 5 |