A study to evaluate efficacy and safety of Vedolizumab in pediatric subjects with moderately to severely active Crohn's disease

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 Crohn’s Disease Who Achieved Clinical Response Following Open–Label Vedolizumab Intravenous Therapy

Status

Not yet recruiting

Phases

Phase 3

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2020-004301-31-LT

Enrollment

120

Registered

2021-04-21

Start date

2021-06-25

Completion date

Unknown

Last updated

2022-08-08

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Moderately to severely active Crohn’s disease (CD) MedDRA version: 20.1 Level: LLT Classification code 10058815 Term: Crohn's disease acute episode System Organ Class: 100000004856

Interventions

Trade Name: ENTYVIO Product Name: Vedolizumab Pharmaceutical Form: Powder for concentrate for solution for infusion INN or Proposed INN: Vedolizumab CAS Number: 943609-66-3 Other descriptive name: MLN

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1. Subjects aged 2 to 17 years, inclusive, who weigh =10 kg at the time of screening and enrollment into the maintenance phase of the study. 2. Subjects with moderately to severely active CD diagnosed at least 1 month before screening, defined by a PCDAI >30 and an SES-CD >6 (or an SES-CD =4 if disease is confined to terminal ileum). 3. Subjects who have failed, lost response to, or been intolerant to treatment with at least 1 of the following agents: corticosteroids, immunomodulators (eg, AZA, 6-mercaptopurine, methotrexate), and/or TNF-a antagonist therapy (eg, infliximab, adalimumab). This includes subjects who are dependent on corticosteroids or exclusive or partial enteral nutrition to control symptoms and who are experiencing worsening of disease in the moderate-to-severe range when attempting to wean off corticosteroids or discontinue exclusive enteral nutrition. 4. 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. 5. 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: 120 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

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 (MAdCAM-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 CD during this study. 7. Subjects who have had subtotal or total colectomy or have a jejunostomy, ileostomy, colostomy, ileo-anal pouch, known fixed stenosis of the intestine, short bowel syndrome, or >3 small intestine resections. 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.

Design outcomes

Primary

Measure	Time frame
Primary end point(s): • Co-primary 1 (based on PCDAI): Clinical remission defined as a PCDAI =10 at Week 54. • Co-primary 2 (based on SES-CD): Endoscopic response at Week 54, where a subject achieves endoscopic response if he or she has at least a 50% reduction in SES-CD score from baseline. ;Main Objective: To evaluate the efficacy of 2 different dose regimens of vedolizumab IV in pediatric subjects with moderately to severely active CD during maintenance therapy, based on clinical and endoscopic assessments at Week 54.;Secondary Objective: To evaluate the efficacy of high and low doses of vedolizumab IV: as measured by clinical and endoscopic remission at W14 and W54;as measured by sustained clinical and endoscopic remission at W54;as measured by sustained clinical response at W54;as measured by sustained endoscopic remission at W54;as measured by sustained clinical remission at W54;To evaluate the effect of high and low doses of vedolizumab IV: on achieving corticosteroid-free remission at W54;on clinical response and clinical remission over time up to W54;To evaluate: vedolizumab PK in pediatric subjects with moderately to severely active CD after IV administration; safety in pediatric subjects on maintenance therapy up to W54; the immunogenicity of vedolizumab in pediatric subjects with moderately to severely active CD treated with vedolizumab IV; the effect of vedolizumab on patterns of growth and pubertal development in pediatric subjects with moderately to severely active CD during their participation in the study.;Timepoint(s) of evaluation of this end point: Week 54	—

Measure

Time frame

Primary end point(s): • Co-primary 1 (based on PCDAI): Clinical remission defined as a PCDAI =10 at Week 54. • Co-primary 2 (based on SES-CD): Endoscopic response at Week 54, where a subject achieves endoscopic response if he or she has at least a 50% reduction in SES-CD score from baseline. ;Main Objective: To evaluate the efficacy of 2 different dose regimens of vedolizumab IV in pediatric subjects with moderately to severely active CD during maintenance therapy, based on clinical and endoscopic assessments at Week 54.;Secondary Objective: To evaluate the efficacy of high and low doses of vedolizumab IV: as measured by clinical and endoscopic remission at W14 and W54;as measured by sustained clinical and endoscopic remission at W54;as measured by sustained clinical response at W54;as measured by sustained endoscopic remission at W54;as measured by sustained clinical remission at W54;To evaluate the effect of high and low doses of vedolizumab IV: on achieving corticosteroid-free remission at W54;on clinical response and clinical remission over time up to W54;To evaluate: vedolizumab PK in pediatric subjects with moderately to severely active CD after IV administration; safety in pediatric subjects on maintenance therapy up to W54; the immunogenicity of vedolizumab in pediatric subjects with moderately to severely active CD treated with vedolizumab IV; the effect of vedolizumab on patterns of growth and pubertal development in pediatric subjects with moderately to severely active CD during their participation in the study.;Timepoint(s) of evaluation of this end point: Week 54

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Secondary

Measure	Time frame
Timepoint(s) of evaluation of this end point: Timepoints of evaluation of secondary endpoints are provided in E.5.2.;Secondary end point(s): •Clinical and endoscopic remission at Week 14, where a subject achieves both clinical and endoscopic remission if he or she meets the following definition: PCDAI =10 and SES-CD =4 with at least a 2-point reduction from baseline and no subscore >1. • Clinical and endoscopic remission at Week 54, where a subject achieves both clinical and endoscopic remission if he or she meets the following definition: PCDAI =10 and SES-CD =4 with at least a 2-point reduction from baseline and no subscore >1. • Sustained clinical and endoscopic remission at Week 54, where a subject achieves sustained clinical and endoscopic remission if he or she achieved clinical and endoscopic remission (based on PCDAI and SES-CD) at Week 14 and at Week 54. • Corticosteroid-free remission at Week 54, where a subject achieves corticosteroid-free clinical remission based on PCDAI at Week 54 and he or she has been off corticosteroids at least 12 weeks before Week 54. • Sustained endoscopic remission, where a subject achieves sustained endoscopic remission if he or she meets the following definition: SES-CD =4 with at least a 2 point reduction from baseline and no subscore >1, achieved at both Weeks 14 and 54. • Sustained clinical remission at Week 54, where a subject achieves sustained clinical remission if he or she achieved clinical remission (based on PCDAI) at Week 14 and at Week 54. • Serum trough concentrations of vedolizumab over time. • Positive antivedolizumab antibody (AVA) and positive neutralizing AVA titers during the study. • Sustained clinical response of subjects at Weeks 14 and 54, where a subject meets clinical response of if he or she has a PCDAI score =30 and reduction of the PCDAI by =15 points from baseline. •Clinical remission at Weeks 2, 6, 10, 14, 22, 30, 38, 46, and 54 where a subject achieves clinical remission if he or she meets the f	—

Measure

Time frame

Timepoint(s) of evaluation of this end point: Timepoints of evaluation of secondary endpoints are provided in E.5.2.;Secondary end point(s): •Clinical and endoscopic remission at Week 14, where a subject achieves both clinical and endoscopic remission if he or she meets the following definition: PCDAI =10 and SES-CD =4 with at least a 2-point reduction from baseline and no subscore >1. • Clinical and endoscopic remission at Week 54, where a subject achieves both clinical and endoscopic remission if he or she meets the following definition: PCDAI =10 and SES-CD =4 with at least a 2-point reduction from baseline and no subscore >1. • Sustained clinical and endoscopic remission at Week 54, where a subject achieves sustained clinical and endoscopic remission if he or she achieved clinical and endoscopic remission (based on PCDAI and SES-CD) at Week 14 and at Week 54. • Corticosteroid-free remission at Week 54, where a subject achieves corticosteroid-free clinical remission based on PCDAI at Week 54 and he or she has been off corticosteroids at least 12 weeks before Week 54. • Sustained endoscopic remission, where a subject achieves sustained endoscopic remission if he or she meets the following definition: SES-CD =4 with at least a 2 point reduction from baseline and no subscore >1, achieved at both Weeks 14 and 54. • Sustained clinical remission at Week 54, where a subject achieves sustained clinical remission if he or she achieved clinical remission (based on PCDAI) at Week 14 and at Week 54. • Serum trough concentrations of vedolizumab over time. • Positive antivedolizumab antibody (AVA) and positive neutralizing AVA titers during the study. • Sustained clinical response of subjects at Weeks 14 and 54, where a subject meets clinical response of if he or she has a PCDAI score =30 and reduction of the PCDAI by =15 points from baseline. •Clinical remission at Weeks 2, 6, 10, 14, 22, 30, 38, 46, and 54 where a subject achieves clinical remission if he or she meets the f

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Countries

Australia, Belgium, Canada, China, Croatia, Czechia, Czech Republic, Greece, Hungary, Israel, Italy, Japan, Korea, Republic of, Lithuania, Poland, Russian Federation, Slovakia, Spain, Ukraine, United Kingdom, United States

Contacts

Public ContactDirector, Clinical Operations

Takeda Development Center Americas, Inc.

mark.patti@takeda.com+1617.444.1281

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026