A Study of Vedolizumab in Children and Teenagers With Moderate to Severe Crohn's Disease (CD)
ConditionCrohn's Disease (CD)
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age2-17
SponsorTakeda
About this trial
Vedolizumab is a medicine that helps to reduce inflammation and pain in the digestive system. In this study, children and teenagers with moderate to severe Crohn's disease will be treated with vedolizumab.
The main aim of the study is to check if participants achieve remission after treatment with the vedolizumab. Remission means symptoms improve or disappear and an endoscopy shows no signs of inflammation.
Participants will receive 3 infusions of vedolizumab over 6 weeks. Then, those who have a clinical response will receive either a high dose or low dose of vedolizumab once every 8 weeks. They will receive the same dose every time.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
The participants has moderately to severely active CD, unresponsive or intolerant to their current standard of care (SOC).
The participants weigh ≥10 kg at the time of screening and enrollment into the study.
Participants with Crohn's disease (CD) diagnosed at least 1 month before screening. Participants with moderately to severely active CD defined by a Pediatric Crohn's Disease Activity Index (PCDAI) >30 and an simple endoscopic score for Crohn's Disease (SES-CD) >6 (or an SES-CD ≥4 if disease is confined to terminal ileum) at screening endoscopy.
Participants who have failed, lost response to, or been intolerant to treatment with at least 1 of the following agents: corticosteroids, immunomodulators (eg, azathioprine (AZA), 6-mercaptopurine (6-MP), methotrexate [MTX]), and/or tumor necrosis factor (TNF)-α antagonist therapy (eg, infliximab, adalimumab). This includes participants 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.
Disqualifiers
Participants 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.
Participants 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.
The participants had a clinically significant infection (eg, pneumonia, pyelonephritis, coronavirus disease 2019 [COVID-19]) within 30 days prior to first dose of study drug.
The participants has received any live vaccinations within 30 days prior to first dose.
Trial design
Design model
Parallel
Treatments tested in this trial
Vedolizumab IV
DrugVedolizumab IV
Treatment groups
120 Participants
are divided into 9 treatment groups9
Treatment groupsSee each treatment group below.
Group A: Induction Period: 10 to 15 kg, Vedolizumab 150 mgExperimental treatment 1 intervention
Group B: Induction Period: >15 to <30 kg, Vedolizumab 200 mgExperimental treatment 1 intervention
Group C: Induction Period: ≥30 kg, Vedolizumab 300 mgExperimental treatment 1 intervention
Group D: Maintenance Period: 10 to 15 kg Vedolizumab 150 mgExperimental treatment 1 intervention
Group E: Maintenance Period: 10 to 15 kg Vedolizumab 100 mgExperimental treatment 1 intervention
Group F: Maintenance Period: >15 to <30 kg, Vedolizumab 200 mgExperimental treatment 1 intervention
Group G: Maintenance Period: >15 to <30 kg Vedolizumab 100 mgExperimental treatment 1 intervention
Group H: Maintenance Period: ≥30 kg, Vedolizumab 300 mgExperimental treatment 1 intervention
Group I: Maintenance Period: ≥30 kg: Vedolizumab 150 mgExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Percentage of Participants With Clinical Remission at Week 54 Based on Pediatric Crohn's Disease Activity Index (PCDAI) Score ≤10
Clinical remission is defined by PCDAI score ≤10. The PCDAI was specifically designed for use in children. The PCDAI includes a child-specific item: the height velocity variable as well as three laboratory parameters: hematocrit (HCT) (adjusted for age and sex), erythrocyte sedimentation rate (ESR), and albumin level. The PCDAI score ranges from 0 to 100, with higher scores indicating more active disease. A score of \<10 will be consistent with inactive disease, 11 to 30 will indicate mild disease, and \>30 will indicate moderate to severe disease. A decrease of 12.5 points is taken as evidence of improvement.
Time frame
Week 542
Percentage of Participants With Endoscopic Response at Week 54 Based on Simple Endoscopic Score for Crohn's Disease [SES-CD] Score
Endoscopic response is defined as at least a 50% reduction in SES-CD score from Baseline. The overall SES-CD score ranges from 0 to 56 and is the sum of 4 variables (ie, size of ulcers \[cm\], ulcerated surface, affected surface \[%\], and presence of narrowing) across 5 bowel segments (ie, rectum, descending and sigmoid colon, transverse colon, ascending colon, and ileum). Each variable is coded from 0 to 3 based on severity, where 0 is none or not severe and 3 is the most severe case, with the sum of the scores for each variable ranging from 0 to 15, except for presence of narrowing. Presence of narrowing ranges from 0 to 11 since a severity of 3 represents a narrowing which a colonoscope cannot be passed and, thus, can only be observed once among the bowel segments. The segmental SES-CD score is the sum of the 4 variables for each bowel segment and can range from 0 to 12, where each individual variable score ranges from 0 to 3.
Time frame
Week 54Secondary outcomes
1
Percentage of Participants with Clinical and Endoscopic Remission at Week 14 Based on Both PCDAI Score and SES-CD Score
Clinical and endoscopic remission is where participant achieves both clinical and endoscopic remission. Clinical remission is defined by PCDAI score ≤10. Endoscopic remission is defined by SES-CD score of ≤4 with at least a 2-point reduction from Baseline and no sub-score \>1. PCDAI includes child-specific item: height velocity variable as well as three laboratory parameters: HCT, ESR, albumin level. PCDAI score ranges from 0 to 100, with higher scores indicating more active disease. The SES-CD score ranges from 0 to 56 and is the sum of 4 variables, size of ulcers \[cm\], ulcerated surface, affected surface \[%\], and presence of narrowing) across 5 bowel segments (ie, rectum, descending and sigmoid colon, transverse colon, ascending colon, and ileum), where higher scores indicate more severe disease.
Time frame
Week 142
Percentage of Participants with Clinical and Endoscopic Remission at Week 54 Based on Both PCDAI Score and SES-CD Score
Clinical and endoscopic remission is where participant achieves both clinical and endoscopic remission. Clinical remission is defined by PCDAI score ≤10. Endoscopic remission is defined by SES-CD score of ≤4 with at least a 2-point reduction from Baseline and no sub-score \>1. PCDAI includes child-specific item: height velocity variable as well as three laboratory parameters: HCT, ESR, albumin level. PCDAI score ranges from 0 to 100, with higher scores indicating more active disease. The SES-CD score ranges from 0 to 56 and is the sum of 4 variables, size of ulcers \[cm\], ulcerated surface, affected surface \[%\], and presence of narrowing) across 5 bowel segments (ie, rectum, descending and sigmoid colon, transverse colon, ascending colon, and ileum), where higher scores indicate more severe disease.
Time frame
Week 543
Percentage of Participants with Sustained Clinical and Endoscopic Remission at Week 54
Sustained clinical and endoscopic remission is where a participant achieved clinical and endoscopic remission based on PCDAI and SES-CD scores at Weeks 14 and 54. Clinical remission is defined by PCDAI score ≤10. Endoscopic remission is defined as ≤4 with at least a 2-point reduction from Baseline and no sub-score \>1 by SES-CD. The PCDAI includes a child-specific item: the height velocity variable as well as three laboratory parameters: HCT, ESR, and albumin level. The PCDAI score ranges from 0 to 100, with higher scores indicating more active disease. The SES-CD score ranges from 0 to 56 and is the sum of 4 variables, size of ulcers \[cm\], ulcerated surface, affected surface \[%\], and presence of narrowing) across 5 bowel segments (ie, rectum, descending and sigmoid colon, transverse colon, ascending colon, and ileum), where higher scores indicate more severe disease.
Time frame
Week 544
Percentage of Participants with Corticosteroid-free Remission at Week 54 Based on PCDAI Score
Corticosteroid-free clinical remission is where participants achieves corticosteroid-free clinical remission based on PCDAI at Week 54 and has been off corticosteroids at least 12 weeks prior to and at Week 54. Clinical remission is defined by PCDAI score ≤10. The PCDAI includes a child-specific item: the height velocity variable as well as three laboratory parameters: HCT, ESR, and albumin level. The PCDAI score ranges from 0 to 100, with higher scores indicating more active disease.
Time frame
Week 54 Source ClinicalTrials.gov