|E.1 Medical condition or disease under investigation
|Medical condition(s) being investigated
|Moderately to severely active Ulcerative Colitis (UC)
|Medical condition in easily understood language
|Moderately to severely active Ulcerative Colitis. UC is a long-term condition that results in inflammation and ulcers of the colon and rectum
|Diseases [C] - Digestive System Diseases [C06]
|E.1.2 Medical condition or disease under investigation
|Acute ulcerative colitis
|System Organ Class
|Condition being studied is a rare disease
|E.2 Objective of the trial
|Main objective of the trial
|To evaluate the efficacy of 2 different dose regimens of vedolizumab IV in pediatric subjects with moderately to severely active UC during maintenance therapy, based on clinical remission at Week 54.
|Secondary objectives of the trial
|To Evaluate Efficacy of high & low doses of vedolizumab IV:
-In paediatric subjects with moderately to severely active UC, based on clinical remission at W14
-As measured by sustained clinical remission at W14&54
-As measured by sustained clinical response at W14&54
-As measured by sustained endoscopic remission at W14&54
-On achieving corticosteroid-free remission at W54
-Effect of high & low doses of vedolizumab IV on clinical response and clinical remission over time up to W54
-Vedolizumab PK in paediatric subjects with moderately to severely active UC after IV admin
-Safety in ped subjects on maintenance therapy up to W54
-The immunogenicity of vedolizumab in paediatric subjects with moderately to severely active UC treated with vedolizumab IV
-The effect of vedolizumab on patterns of growth and pubertal development in paediatric subjects with moderately to severely active UC during their study participation
|Trial contains a sub-study
|Principal inclusion criteria
|1. The subjects aged 2 to 17 years, inclusive, at the time of screening and enrollment into the maintenance phase of the study.
2. The subject weighs ≥10 kg at the time of screening and enrollment into the study.
3. Subjects with moderately to severely active UC diagnosed at least 1 month before screening, defined by a modified Mayo score of 5 to 9 (sum of Mayo endoscopic subscore, stool frequency subscore, and rectal bleeding subscore) with a Mayo endoscopic subscore of ≥2 (with the presence of mucosal friability excluding an endoscopic subscore of 1 and mandating a score of at least 2).
4. Subjects who have failed, lost response to, or been intolerant to treatment with at least 1 of the following agents: corticosteroids, immunomodulators (eg, azathioprine, 6-mercaptopurine, methotrexate), and/or TNF-α antagonist therapy (eg, infliximab, adalimumab). This includes subjects who are dependent on corticosteroids to control symptoms and who are experiencing worsening of disease when attempting to wean off corticosteroids.
5. Subjects with evidence of UC extending proximal to the rectum (ie, not limited to proctitis), at a minimum.
6. Subjects with extensive colitis or pancolitis of >8 years’ duration or left-sided colitis of >12 years’ duration must have documented evidence of a negative surveillance colonoscopy within 12 months before screening.
7. Subjects with vaccinations that are up to date based on the countrywide, accepted schedule of childhood vaccines.
|Principal exclusion criteria
|1. Subjects who have had previous exposure to approved or investigational anti-integrins including, but not limited to natalizumab, efalizumab, etrolizumab, or AMG 181, or mucosal addressin cell adhesion molecule-1 antagonists or rituximab.
2. Subjects who have had prior exposure to vedolizumab.
3. Subjects with hypersensitivity or allergies to any of the vedolizumab excipients.
4. Subjects who have received either (1) an investigational biologic (other than those listed in Exclusion Criterion #1) within 60 days or 5 half-lives before screening (whichever is longer); or (2) an approved biologic or biosimilar agent within 2 weeks before the first dose of study drug or at any time during the screening period.
5. Subjects with active cerebral/meningeal disease, signs/symptoms or history of progressive multifocal leukoencephalopathy (PML) or any other major neurological disorders including stroke, multiple sclerosis, brain tumor or neurodegenerative disease.
6. Subjects who currently require surgical intervention or are anticipated to require surgical intervention for UC during this study.
7. Subjects who have had subtotal or total colectomy or have a jejunostomy, ileostomy, colostomy, ileo-anal pouch, or known fixed stenosis of the intestine.
8. Subjects with a current diagnosis of indeterminate colitis.
9. Subjects with clinical features suggesting monogenic very early onset inflammatory bowel disease.
10. The subject has other serious comorbidities that will limit his or her ability to complete the study
|E.5 End points
|Primary end point(s)
|The primary endpoint is clinical remission at Week 54, where clinical remission based on the modified Mayo score is defined as:
• stool frequency subscore 0 to 1 and a decrease of 1 or more from baseline;
• rectal bleeding subscore of 0;
• endoscopy subscore 0 to 1 (modified so that a score of 1 does not include friability).
|Timepoint(s) of evaluation of this end point
|Secondary end point(s)
|• Clinical remission at Week 14, where a subject achieves clinical remission if he or she meets the definition described in the primary endpoint.
• Sustained clinical remission at Week 54, where a subject achieves sustained clinical remission if he or she achieved clinical remission (as defined by primary endpoint) at Week 14 and at Week 54.
• Sustained endoscopic remission, defined as Mayo endoscopic score (MES) of ≤1 point, at Week 14 and at Week 54.
• Endoscopic response, defined as a decrease in MES ≥1 grade at Week 14 and at Week 54.
• Corticosteroid-free clinical remission at Week 54, where a subject achieves corticosteroid-free clinical remission at Week 54 if he or she meets the definition described in the primary endpoint and was off corticosteroids at least 12 weeks before Week 54.
• Clinical remission based on complete Mayo score at Week 54, where a subject achieves clinical remission if he or she achieved a complete Mayo score ≤2 points with no individual subscore >1 at Week 54.
• Serum trough concentrations of vedolizumab over time.
• Positive antivedolizumab antibodies (AVA) and positive neutralizing AVA during the study.
• Sustained clinical response of subjects at Weeks 14 and 54, where a subject meets clinical response if he or she has a reduction in complete Mayo score (see Appendix G) of ≥3 points and ≥30% from baseline with an accompanying decrease in rectal bleeding subscore of ≥1 point or absolute rectal bleeding subscore of ≤1 point.
• Clinical response at Weeks 2, 6, 10, 14, 22, 30, 38, 46, and 54 where a subject achieves clinical response if he or she meets the following definition:
• Reduction of ≥2 points and ≥25% from the baseline partial Mayo score, including a ≥1-point decrease in the Mayo stool frequency subscore and a ≥1-point reduction in the rectal bleeding subscore or absolute rectal bleeding subscore of ≤1 point;
• Safety assessments: descriptions of adverse events (AEs); serious adverse events (SAEs); and adverse events of special interest (AESIs), including evaluation of opportunistic infection, such as PML, liver injury, malignancies, infusion-related reactions, and hypersensitivity.
• Change from baseline in weight gain and linear growth z-score during the course of dosing with vedolizumab.
• Tanner Stage V at Week 54, where a subject achieves Tanner Stage V at Week 54 based on progression of pubertal changes from baseline.
|Timepoint(s) of evaluation of this end point
|Timepoints of secondary end points are provided in E.5.2.
|E.6 and E.7 Scope of the trial
|Scope of the trial
|Other scope of the trial description
|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)
|Different doses of IMP are used in treatment arms
|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
|Korea, Republic of
|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
|In all countries concerned by the trial days