Colitis, Ulcerative
Conditions
Keywords
Drug Therapy
Brief summary
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 ulcerative colitis will be treated with vedolizumab. The main aim of the study is to check if participants achieve remission after treatment with vedolizumab. Remission means symptoms improve or disappear and an endoscopy shows no or limited signs of disease. The study is also evaluating side effects of vedolizumab in the children and teenager with moderately to severely active ulcerative colitis. Participants will receive 3 infusions of vedolizumab over 6 weeks. Then, those who have a clinical response will receive 1 of 3 doses of vedolizumab once every 8 weeks. They will receive the same dose every time.
Detailed description
The drug being tested in this study is called vedolizumab. Vedolizumab is being tested to treat pediatric participants who have moderately to severely active UC. Participants to be enrolled must have failed response to, lost response to, or been intolerant to at least 1 of the current standard of care (SOC) induction and maintenance therapies for UC including immunomodulators (eg, azathioprine \[AZA\], 6-mercaptopurine \[6-MP\], methotrexate \[MTX\]), and tumor necrosis factor-alpha (TNF-α) antagonists (eg, infliximab, adalimumab). The study will enroll approximately 120 patients. During the Induction Period participants will receive 3 doses of vedolizumab IV infusion at Day 1, Week 2, and Week 6 based on their weight at Baseline: * Participants ≥30 kg, Vedolizumab 300 mg * Participants \>15 to \<30 kg, Vedolizumab 200 mg * Participants 10 to 15 kg, Vedolizumab 150 mg At Week 14, participants who achieve clinical response will be randomly assigned (by chance, like flipping a coin) in a 1:1 ratio to one of the 2 double-blind dose groups (high dose and low dose), stratified by previous exposure/failure to TNF-α antagonists therapy or naive to TNF-α antagonists therapy, and weight. Participants will receive vedolizumab IV infusions every 8 weeks (Q8W) up to Week 46 during the Maintenance Period as follows: * Participants ≥30 kg, Vedolizumab 300 mg (High dose) or 150 mg (Low dose) * Participants \>15 to \<30 kg, Vedolizumab 200 mg (High dose) or 100 mg (Low dose) * Participants 10 to 15 kg, Vedolizumab 150 mg (High dose) or 100 mg (Low dose) The dose will remain blinded to the participant and study doctor and staff during the study (unless there is an urgent medical need). All participants will be administered vedolizumab via IV infusion. In participants who demonstrate lack of maintenance of clinical response during the Maintenance Period the dose will be escalated in a blinded fashion based on the weight at the time of the worsening of disease. In addition one-time rescue therapy with corticosteroids is allowed during Maintenance period. This multi-center trial will be conducted worldwide. After the Week 54 visit, participants who are younger than 18 years may be eligible to continue receiving vedolizumab in extension study MLN0002-3029 (NCT05442567). Participants who do not maintain corticosteroid-free clinical response at Week 54 or who discontinue study drug at any time during the induction or maintenance periods of this study will undergo an end of study (EOS) or early termination (ET) visit, as well as a safety visit 18 weeks after the last dose of vedolizumab, in addition these participants would enter study MLN0002-3029 for an observational long-term follow-up (LTFU) period of 2 years after the last dose of study drug in the current study. During the LTFU period, data will be collected either by clinic visit OR, if site attendance is not feasible, by phone call every 6 months.
Interventions
DRUGVedolizumab
Vedolizumab IV infusion.
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
2 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
1. Has moderately to severely active UC, unresponsive or intolerant to their current standard of care (SOC). 2. Weighs ≥10 kg at the time of screening and enrollment into the study. 3. Participants with UC diagnosed at least 1 month before screening. Participants with moderately to severely active UC based on 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) at screening endoscopy. 4. Has failed, lost response to, or been intolerant to treatment with at least 1 of the following agents: corticosteroids (eg, azathioprine \[AZA\], 6-mercaptopurine \[6-MP\], methotrexate \[MTX\]), immunomodulators, and/or tumor necrosis factor alpha (TNF-α) antagonist therapy (eg, infliximab, adalimumab). This includes participants who are dependent on corticosteroids to control symptoms and who are experiencing worsening of disease in the moderate-to-severe range when attempting to wean off corticosteroids. 5. Has evidence of UC extending proximal to the rectum (i.e., not limited to proctitis), at a minimum. 6. Has 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. Participants with vaccinations that are up-to-date based on the countrywide, accepted schedule of childhood vaccines.
Exclusion criteria
1. Has previous exposure to approved or investigational anti-integrins including, but not limited to natalizumab, efalizumab, etrolizumab, or Abrilumab (AMG 181), or mucosal addressin cell adhesion molecule-1 (MAdCAM-1) antagonists or rituximab. 2. Has received an investigational biologic within 60 days or 5 half-lives before screening (whichever is longer); or an approved biologic or biosimilar agent within 2 weeks before the first dose of study drug or at any time during the screening period. 3. Has 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. 4. Has had clinically significant infection (eg, pneumonia, pyelonephritis, coronavirus disease 2019 \[COVID-19\]) within 30 days prior to first dose of study drug. 5. Has received any live vaccinations within 30 days prior to first dose of study drug. 6. Participants who currently require surgical intervention or are anticipated to require surgical intervention for UC during this study. 7. Has had subtotal or total colectomy or have a jejunostomy, ileostomy, colostomy, ileo-anal pouch, or known fixed stenosis of the intestine. 8. Participants with a current diagnosis of indeterminate colitis. 9. Participants with clinical features suggesting monogenic very early onset inflammatory bowel disease. 10. Participant with 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. NOTE: If participants have received Bacillus Calmette-Guérin vaccine then a QuantiFERON TB Gold test should be performed instead of the TB skin test. 11. Participants with evidence of positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb). Hepatitis B virus (HBV) immune participants (ie, 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. Participants with chronic hepatitis C virus (HCV) (ie, positive HCV antibody \[HCVAb\] and HCV RNA). Note: Subjects 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 participant has evidence of dysplasia or history of malignancy other than a successfully treated nonmetastatic cutaneous squamous cell or basal cell carcinoma or localized carcinoma in situ of the cervix. 13. Has positive stool studies for ova and/or parasites or stool culture at screening visit. 14. Has positive Clostridioides difficile (C difficile) stool test at screening visit. Other inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Clinical Remission at Week 54 Based on Modified Mayo Score | At Week 54 | Clinical remission based on the modified Mayo score was defined as stool frequency sub score 0 to 1 and a decrease of 1 or more from baseline, rectal bleeding sub score of 0, and endoscopy sub score 0 to 1 (modified so that a score of 1 does not include friability) and without presence of any intercurrent event. Mayo score was an instrument designed to measure disease activity of UC. Modified Mayo score was a composite index of 3 disease activity variables (stool frequency, rectal bleeding, and endoscopy). Each subscale was graded from 0 to 3 where higher score indicated more severe disease. These scores were summed to give a total score range of 0 to 9 where, higher score indicated more severe disease. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Clinical Remission at Week 14 Based on Modified Mayo Score | At Week 14 | Clinical remission based on the modified Mayo score was defined as stool frequency sub score 0 to 1 and a decrease of 1 or more from baseline, rectal bleeding sub score of 0, and endoscopy sub score 0 to 1 (modified so that a score of 1 does not include friability) and without presence of any intercurrent event. Mayo score was an instrument designed to measure disease activity of UC. Modified Mayo score was a composite index of 3 disease activity variables (stool frequency, rectal bleeding, and endoscopy. Each subscale was graded from 0 to 3 where higher score indicated more severe disease. These scores were summed to give a total score range of 0 to 9 where, higher score indicated more severe disease. |
| Percentage of Participants With Sustained Clinical Remission at Week 54 Based on Modified Mayo Score | At Week 54 | Participants who had clinical remission at Week 14 were analyzed for sustained clinical remission at Week 54. Clinical remission based on the modified Mayo score was defined as stool frequency sub score 0 to 1 and a decrease of 1 or more from baseline, rectal bleeding sub score of 0, and endoscopy sub score 0 to 1 (modified so that a score of 1 does not include friability) and without presence of any intercurrent event. Mayo score was an instrument designed to measure disease activity of UC. Modified Mayo score was a composite index of 3 disease activity variables (stool frequency, rectal bleeding, and endoscopy. Each subscale was graded from 0 to 3 where higher score indicated more severe disease. These scores were summed to give a total score range of 0 to 9 where, higher score indicated more severe disease. |
| Percentage of Participants With Sustained Endoscopic Remission at Week 54 | At Week 54 | Participants who had endoscopic remission at Week 14 were analyzed for sustained endoscopic remission at Week 54. Mayo endoscopic sub score (MES) was a subscale of the Mayo score, an instrument designed to measure disease activity of UC. The subscale was graded from 0 to 3 based on the findings on endoscopy where 0=normal or inactive disease, 1=mild disease (erythema, decreased vascular pattern), 2=moderate disease (marked erythema, lack of vascular pattern, friability, erosions), 3=severe disease (spontaneous bleeding, ulceration). Higher score indicated more severe disease. |
| Percentage of Participants With Endoscopic Response at Week 14 | At Week 14 | Endoscopic response was defined as a decrease from baseline in the MES \>=1 point. MES was a subscale of the Mayo score, an instrument designed to measure disease activity of UC. The subscale was graded from 0 to 3 based on the findings on endoscopy where 0=normal or inactive disease, 1=mild disease (erythema, decreased vascular pattern), 2=moderate disease (marked erythema, lack of vascular pattern, friability, erosions), 3=severe disease (spontaneous bleeding, ulceration). Higher score indicated more severe disease. |
| Percentage of Participants With Endoscopic Response at Week 54 | At Week 54 | Endoscopic response was defined as a decrease from baseline in the MES \>=1 point. MES was a subscale of the Mayo score, an instrument designed to measure disease activity of UC. The subscale was graded from 0 to 3 based on the findings on endoscopy where 0=normal or inactive disease, 1=mild disease (erythema, decreased vascular pattern), 2=moderate disease (marked erythema, lack of vascular pattern, friability, erosions), 3=severe disease (spontaneous bleeding, ulceration). Higher score indicated more severe disease. |
| Percentage of Participants With Corticosteroid-free Clinical Remission at Week 54 | At Week 54 | Corticosteroid-free clinical remission based on the modified Mayo score was defined as when a participant meets the definition described in the primary endpoint and was off corticosteroids at least 12 weeks prior to and at Week 54 and without presence of any intercurrent event. Modified Mayo score was a composite index of 3 disease activity variables (stool frequency, rectal bleeding, and endoscopy. Each subscale was graded from 0 to 3 where higher score indicated more severe disease. These scores were summed to give a total score range of 0 to 9 where, higher score indicated more severe disease. |
| Percentage of Participants With Clinical Remission at Week 54 Based on Complete Mayo Score | At Week 54 | Clinical remission based on complete Mayo score was a score (inclusive of physician global assessment \[PGA\]) of \<=2 points with no individual sub score \>1 and without presence of any intercurrent event. Mayo score was an instrument designed to measure disease activity of UC. Complete Mayo score was a composite index of 4 disease activity variables (stool frequency, rectal bleeding, endoscopy \[modified so that a score of 1 does not include friability\], and PGA sub scores) ranging from 0-12. Higher score indicated more severe disease. |
| Serum Trough Concentrations of Vedolizumab Over Time | Predose at Week 14 and post dose at Week 54 | Serum trough concentration of vedolizumab was reported. |
| Percentage of Participants With Positive Anti-vedolizumab Antibodies (AVA) | Up to Week 54 | AVA positive was defined as a confirmed AVA positive result. |
| Percentage of Participants With Positive Neutralizing AVA | Up to Week 54 | Positive Neutralizing AVA was defined as a positive result in the neutralizing AVA assay at any visit. |
| Percentage of Participants With Sustained Clinical Response at Week 54 Based on Complete Mayo Score | At Week 54 | Participants who had clinical response at Week 14 were analyzed for sustained clinical response at Week 54. Sustained refers to meeting the specific endpoint criteria at both Week 14 and Week 54. Sustained clinical response is defined as meeting the following criteria at both Week 14 and Week 54: reduction in complete Mayo score of \>=3 points and \>=30% from baseline with an accompanying decrease in rectal bleeding sub score of \>=1 point or absolute rectal bleeding sub score of \<=1 point. Mayo score was an instrument designed to measure disease activity of UC. Complete Mayo score was a composite index of 4 disease activity variables (stool frequency, rectal bleeding, endoscopy \[modified so that a score of 1 does not include friability\], and PGA sub scores) ranging from 0-12. Higher score indicated more severe disease. |
| Percentage of Participants With Clinical Response up to Week 54 Based on Partial Mayo Score | At Weeks 2, 6, 10, 14, 22, 30, 38, 46, and 54 | Clinical response was where a participant achieved clinical response if they had a reduction of \>=2 points and \>=25% from the baseline partial Mayo score, including a \>=1 point decrease in the Mayo stool frequency sub score and a \>=1 point reduction in the rectal bleeding sub score or absolute rectal bleeding sub score of \<=1 point. Mayo score was an instrument designed to measure disease activity of UC. A partial Mayo score was defined as composite index of 3 disease activity variables (stool frequency, rectal bleeding, and PGA sub scores) that ranged from 0-9 and excluded the endoscopy sub score. Higher score indicates more severe disease. |
| Percentage of Participants With Clinical Remission up to Week 54 Based on Partial Mayo Score | At Weeks 2, 6, 10, 14, 22, 30, 38, 46, and 54 | Clinical remission based on partial Mayo score was defined as a partial Mayo score of \<=2 points and no individual sub score \>1 point. Mayo score was an instrument designed to measure disease activity of UC. A partial Mayo score was defined as composite index of 3 disease activity variables (stool frequency, rectal bleeding, and PGA sub scores) that ranged from 0-9 and excluded the endoscopy sub score. Higher score indicates more severe disease. |
| Percentage of Participants With at Least One Treatment Emergent Adverse Event (TEAE), Treatment Emergent Serious Adverse Event (TESAE), and Adverse Event of Special Interest (AESI) | From first dose of study drug up to end of follow up (up to 3.7 years) | A TEAE was defined as an AE whose date of onset occurred on or after the first dose of study drug through Week 54 for participants entering the extension study or the final safety visit 18 weeks after their last dose of study drug for those who do not enter the extension study or those who early terminate. A TESAE was defined as an undesirable event that was not present prior to medical treatment or an already present event that worsened either in intensity or frequency following the first dose of study drug, that occurred from the first dose of study drug to the day of last dose of study drug + 126 days. AESI was defined as an AE (serious or nonserious) of medical concern specific to the compound or program, for which ongoing monitoring and rapid communication by the investigator to the sponsor was appropriate. AESIs include infusion-related reactions and hypersensitivity, serious infection, malignancy, or other (liver injury and progressive multifocal leukoencephalopathy \[PML\]). |
| Change From Baseline in Weight | At Weeks 2, 6, 10, 14, 22, 30, 38, 46, and 54 | Change from baseline in weight was reported. |
| Change From Baseline in Weight Z-score | At Weeks 2, 6, 10, 14, 22, 30, 38, 46, and 54 | Change from baseline in weight Z-score was reported. Weight z-score expresses how an individual's measured weight compares to the expected weight of a reference population of the same age and sex, standardized using population growth charts. It represents the number of standard deviations (SDs) an individual's weight is above or below the mean of the reference population. Z-score was calculated as: Z-score = (observed value - median value of the reference population) / standard deviation value of reference population. A Z-score of 0 represents the mean of the reference population. A negative Z-score indicates that the observed value is below (lower than) the reference mean, while a positive Z-score indicates that the observed value is above (higher than) the reference mean. |
| Change From Baseline in Height | At Weeks 2, 6, 10, 14, 22, 30, 38, 46, and 54 | Change from baseline in height was reported. |
| Change From Baseline in Linear Growth Z-score | At Weeks 2, 6, 10, 14, 22, 30, 38, 46, and 54 | Change from baseline in linear growth Z-score were reported. Linear growth Z-score is a standardized measure that describes how far a measured height deviates from the median height of a reference population of the same age and sex based on established growth charts. It is expressed in units of standard deviations (SD). Z-score was calculated as: Z-score = (observed value - median value of the reference population) / standard deviation value of reference population. A Z-score of 0 represents the mean of the reference population. A negative Z-score indicates that the observed value is below (lower than) the reference mean, while a positive Z-score indicates that the observed value is above (higher than) the reference mean. |
| Number of Participants With Change From Baseline in Tanner Stage at Week 54 | At Week 54 | Tanner stages are used to evaluate growth parameters. They are standardized for age, sex, and pubertal development, with Stage 1 representing the prepubertal stage and Stage 5 representing the fully mature adult stage. It measures Female pubertal development staged by pubic hair development and breast size; male pubertal development staged by size of the genitalia and development of pubic hair. Rated in 5 stages: stage 1 (no development) to 5 (adult-like development in quantity and size). The data reported shows shifts in participants' Tanner stages from baseline to Week 54. |
Countries
Australia, Belgium, Canada, China, Croatia, Greece, Hungary, Israel, Italy, Japan, Poland, South Korea, United Kingdom, United States
Participant flow
Recruitment details
The study was conducted across 43 investigative sites in the United States, Asia/Australia, Europe, and Israel from 19 October 2021 to 1 July 2025.
Pre-assignment details
A total of 121 participants with ulcerative colitis (UC) were enrolled. Study has two periods: a 14-week induction phase and a 40-week maintenance phase. Participants who achieved a clinical response at Week 14 were stratified by previous exposure/failure to tumor necrosis factor -alpha (TNF-α) or naive TNF-α antagonist therapy and by weight group (greater than or equal to \[\>=\]30kg; less than \[\>\]15 kg to \<30 kg; 10 kg to 15 kg) were randomized to receive vedolizumab in maintenance period.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 11.9 years STANDARD_DEVIATION 4.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 26 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 26 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 80 Participants |
| Sex: Female, Male Female | 63 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 27 | 0 / 90 | 0 / 47 | 0 / 46 |
| other Total, other adverse events | 3 / 3 | 16 / 27 | 34 / 90 | 28 / 47 | 22 / 46 |
| serious Total, serious adverse events | 0 / 3 | 4 / 27 | 9 / 90 | 3 / 47 | 5 / 46 |
Outcome results
None listed