A Study of Vedolizumab in Children and Teenagers With Moderate to Severe Crohn's Disease

Recruiting

• Conditions: Crohn's Disease

• Registration Number: jRCT2071210031
• Lead Sponsor: Takeda Pharmaceutical Company Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-06-01
• Study Start: 2022-04-30
• Last Update Posted: 2025-01-29

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

1. The participants has moderately to severely active CD, unresponsive or intolerant to their current standard of care (SOC).
2. The participants weigh >=10 kg at the time of screening and enrollment into the study.
3. 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.
4. 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)-alfa 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.
5. Participants 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. Participants with vaccinations that are up-to-date based on the countrywide accepted schedule of childhood vaccines.

Exclusion Criteria

1. Participants who have received either (1) an investigational biologic 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.
2. 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.
3. 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.
4. The participants has received any live vaccinations within 30 days prior to first dose.
5. Participants who currently require surgical intervention or are anticipated to require surgical intervention for CD during this study.
6. Participants 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.
7. Participants with a current diagnosis of indeterminate colitis.
8. Participants with clinical features suggesting monogenic very early-onset inflammatory bowel disease.
9. Active or latent tuberculosis (TB), as evidenced by a diagnostic TB test performed within 30 days of screening or during the screening Period that is positive, defined as:

• Positive QuantiFERON test or 2 successive indeterminate QuantiFERON tests, OR
• A TB skin test reaction >=5 mm.

10. Participants with evidence of positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb). Hepatitis B virus (HBV) immune participants (i.e., hepatitis B surface antigen [HBsAg]-negative and hepatitis B antibody-positive) may, however, be included. Note: If a participant tests negative for HBsAg, but positive for HBcAb, the participant would be considered eligible if the absence of HBV DNA is confirmed by HBV DNA polymerase chain reaction reflex testing performed in the central laboratory.
11. Participants with chronic hepatitis C virus (HCV) (ie, positive HCV antibody [HCVAb] and HCV RNA). Note: Participants who are HCVAb-positive without evidence of HCV RNA may be considered eligible (spontaneous viral clearance or previously treated and cured [defined as no evidence of HCV RNA at least 12 weeks before baseline]).
12. The participants has any identified congenital or acquired immunodeficiency (eg, common variable immunodeficiency, human immunodeficiency virus [HIV] infection, organ transplantation).
13. The participant has evidence of dysplasia or history of malignancy other than a successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma or localized carcinoma in situ of the cervix.
14. Participants with positive stool studies for ova and/or parasites or stool culture at screening visit.
15. Participants with positive Clostridioides difficile (C difficile) stool test at screening visit.

Other inclusion/exclusion criteria may apply.

Study & Design

• Study Type: Interventional
• Study Design: parallel assignment

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Clinical Remission at Week 54 Based on Pediatric Crohn's Disease Activity Index (PCDAI) Score =<10	Week 54	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.
Percentage of Participants With Endoscopic Response at Week 54 Based on Simple Endoscopic Score for Crohn's Disease [SES-CD] Score	Week 54	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.