A study to evaluate efficacy and safety of Vedolizumab in pediatric subjects with moderately to severely active Ulcerative Colitis

• Register: EUCTR
• Last refreshed on: 3 December 2024
• Main ID: EUCTR2020-004300-34-IT
• Date of registration: 30/08/2021
• Prospective Registration: Yes
• Primary sponsor: TAKEDA DEVELOPMENT CENTER AMERICAS INC.
• Public title: A study to evaluate efficacy and safety of Vedolizumab in pediatric subjects with moderately to severely active Ulcerative Colitis
• Scientific title: A Randomized, Double-Blind, Phase 3 Study to Evaluate the Efficacy and Safety of Vedolizumab Intravenous as Maintenance Therapy in Pediatric Subjects with Moderately to Severely Active Ulcerative Colitis Who Achieved Clinical Response Following Open–Label Vedolizumab Intravenous Therapy - NA
• Date of first enrolment: 13/10/2021
• Target sample size: 120
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-004300-34
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: yes Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: Different doses of IMP are used in treatment arms Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Austria, Belgium, Bosnia and Herzegovina, Canada, China, Croatia, Czech Republic, Czechia, France, Germany, Greece, Hungary, Israel, Italy, Japan, Lithuania, New Zealand, Poland, Romania, Russian Federation, Slovakia, Spain, Ukraine, United Kingdom, United States

Contacts

• Name: Director, Clinical Operations
• Affiliation: Takeda Development Center Americas, Inc.

• Name: Director, Clinical Operations
• Affiliation: Takeda Development Center Americas, Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Subjects male or female aged 2 to 17 years, inclusive, who weigh =10 kg at the time of screening and enrollment into the study.
2. 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 (mucosal friability indicates an endoscopic subscore of at least 2).
3. 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-a 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.
4. Subjects with evidence of UC extending proximal to the rectum (ie, not limited to proctitis), at a minimum.
5. 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.
6. Subjects with vaccinations that are up-to-date based on the countrywide, accepted schedule of childhood vaccines.
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Moderately to severely active Ulcerative Colitis (UC)
MedDRA version: 20.1 Level: LLT Classification code 10066678 Term: Acute ulcerative colitis System Organ Class: 100000004856

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Intervention(s)

Trade Name: ENTYVIO - 300 MG - POLVERE PE RCONCENTRATO PER SOLUZIONE PER INFUSIONE - USO ENDOVENOSO - FLACONCINO (VETRO) (20ML) - 1 FLACONCINO
Product Name: Vedolizumab
Product Code: [NA]
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: Vedolizumab
CAS Number: 943609-66-3
Current Sponsor code: NA
Other descriptive name: MLN0002
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 100-300

Primary Outcome(s)

Main Objective: 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 Objective: • To evaluate the efficacy of high and low doses of vedolizumab IV as measured by sustained clinical and endoscopic remission at Weeks 14 and 54.
• To evaluate the effect of high and low doses of vedolizumab IV in each weight group on achieving corticosteroid-free remission at Week 54.
• To evaluate the effect of vedolizumab IV in each weight group on clinical response and clinical remission over time up to Week 54.
• To characterize the exposure of 2 different regimens of vedolizumab in pediatric subjects with moderately to severely active UC after IV administration.
• To evaluate safety in pediatric subjects on maintenance therapy up to Week 54.
• To evaluate the immunogenicity of vedolizumab in pediatric subjects with moderately to severely active UC treated with vedolizumab IV.
• To evaluate the effect of vedolizumab on patterns of growth and pubertal development in pediatric subjects with moderately to severely active UC during their participation in the study.

Timepoint(s) of evaluation of this end point: The end of study is defined as the Week 54 study visit.

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).

Secondary Outcome(s)

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.
• 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 prior to 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.
• Clinical remission based on PUCAI score at Week 54, where a subject achieves clinical remission if he or she has a PUCAI of =10 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:
• Maintenance of a 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; and a =20point decrease from baseline in the PUCAI score for Weeks 2, 6, 10, 14, 22, 30, 38, 46, and 54.
• 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: LSVS

Secondary ID(s)

2020-004300-34-LT

MLN0002-3024

009125

Source(s) of Monetary Support

Takeda Development Center Americas, Inc.

Ethics review

Status: Approved
Approval date: 13/10/2021
Contact: