E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The purpose of the trial is 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 ulcerative colitis (UC). |
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E.1.1.1 | Medical condition in easily understood language |
Moderately or severely active ulcerative colitis (UC). |
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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 moderate or severe UC. |
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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 moderate or severe UC. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
A subject aged 15 to 80 (inclusive) at the time of signing the informed consent. - Subjects with diagnosis of total or left-sided UC based on the Revised Diagnostic Criteria for UC issued by “Research Group for Intractable Inflammatory Bowel Disease” Designated as Specified Disease by the Ministry of Health, Labor and Welfare (MHLW) of Japan (2012) at least 6 months before the start of administration of the study drug. - A subject with moderately or severely active UC as determined by baseline complete Mayo score of 6 to 12 (inclusive) with an endoscopic subscore of ≥2. - Subjects whose complication of colon cancer or dysplasia had to be ruled out by total colonoscopy at the start of the study drug administration (or the results from total colonoscopy performed within 1 year before giving consent are available), if subjects met any of the following criteria; subjects with ≥8-year history of total or left-sided colitis, subjects aged ≥50 years, or subjects with a first-degree family history of colon cancer. - Subjects meeting the following treatment failure criteria with at least one of the following agents within 5 year before the time of signing on the informed consent form: Corticosteroids (steroids) - Resistance - Dependence - Intolerance Immunomodulators [azathioprine (AZA) or 6-mercaptopurine (6-MP)] - Refractory - Intolerance TNF-alfa antagonist - Inadequate response - Loss of response - Intolerance |
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E.4 | Principal exclusion criteria |
Subjects whose partial Mayo score decreased by 3 points or more between screening and the start of the study drug administration. - Subjects having or suspected to have abdominal abscess or toxic megacolon. - Subjects with a history of subtotal or total colectomy. - Subjects with ileostomy, colostomy, fistula or severe intestinal stenosis. - Subjects who started oral 5-aminosalicylic acids (5-ASAs), probiotics, or oral corticosteroids (≤30 mg/day) within 13 days before the first dose of the study drug. Subjects who have used these drugs for at least 14 days before the first dose of the study drug, and who changed dosage of or discontinued these drugs within 13 days before the first dose of the study drug. - Subjects who have used 5-ASAs, corticosteroid enemas/suppositories, corticosteroid IV infusion, oral corticosteroid at >30 mg/day, drugs for diarrhea-predominant irritable bowel syndrome, or Chinese herbal medicine for the treatment of UC (e.g., Daikenchuto) within 13 days before the first dose of the study drug. - Subjects who have used an antidiarrheal drug for 4 or more consecutive days within 13 days before the first dose of the study drug or within 7 days before the first dose of the study drug. - Subjects who have used AZA or 6-MP within 27 days before the first dose of the study drug However, this will not apply to subjects who have used these drugs for 83 or more days before the first dose of the study drug and continued the steady dose administration of the drugs for 27 or more days before the first dose of the study drug. - Subjects who have received cyclosporine, tacrolimus, methotrexate, tofacitinib or any study drugs of low-molecular compound for UC treatment within 27 days before the first dose of the study drug. - Subjects who have received adalimumab within 27 days before the first dose of the study drug or any biologic agents other than adalimumab within 55 days before the first dose of the study drug. However, this will not apply to subjects who have topically received these drugs (e.g., intraocular injection for treatment of age-related macular degeneration). - Subjects who have received any live-vaccinations within 27 days before the first dose of the study drug. - Subjects who have undergone an enterectomy within 27 days before the first dose of the study drug or those anticipated to require the enterectomy during the study. - Subjects who have received leukocytapheresis or granulocyte apheresis within 27 days before the first dose of the study drug. - Subjects with an evidence of adenomatous colonic polyps that need to be removed at the start of the study drug administration. - Subjects with a history or a complication of colonic mucosal dysplasia. |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Clinical response at Week 10 in Induction Phase - Clinical remission at Week 60 in Maintenance Phase |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
- Week 10 in Induction Phase - Week 60 in Maintenance Phase |
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E.5.2 | Secondary end point(s) |
- Clinical remission and mucosal healing in Induction Phase - Durable response, mucosal healing, durable remission, and corticosteroid-free remission in Maintenance Phase |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Week 10 in Induction Phase - Week 60 in Maintenance Phase |
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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 | 3 |
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 will be performed at 16 weeks after the last dose in all subjects who received the study drug. In addition, the follow-up survey will be 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 | 3 |
E.8.9.2 | In all countries concerned by the trial months | 3 |