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A Study of Vedolizumab in Children and Teenagers With Moderate to Severe Crohn's Disease (CD)
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.
Study details:
The drug being tested in this study is called vedolizumab. Vedolizumab is being tested to treat pediatric participants who have moderately to severely active CD. The drug is tested and approved in adults in approximately 70 countries.
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 CD including exclusive and/or partial enteral nutrition therapy, immunomodulators (e. g. , azathioprine \[AZA\], 6-mercaptopurine \[6-MP\], methotrexate \[MTX\]), and tumor necrosis factor-alpha (TNF-α) antagonists.
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 as:. * Participants 10 to 15 kg, Vedolizumab 150 mg.
* Participants \>15 to \<30 kg, Vedolizumab 200 mg. * Participants ≥30 kg, Vedolizumab 300 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 by weight groups.
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) 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 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 to the high dose in their weight group 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, participants may be eligible to continue receiving vedolizumab in extension study MLN0002-3029. Participants who do not maintain corticosteroid-free clinical response at week 54 will undergo an end-of-study (EOS) or ET visit, and a safety visit 18 weeks after the last dose of vedolizumab followed by 2 years of long term follow-up (up to 104 weeks), in addition these participants will then be eligible to enter study MLN0002-3029 for an observational LTFU period of 2 years after the last dose of study drug.
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
Inclusion criteria
Exclusion criteria
Eligibility
Age eligible for study : 2 and older
Healthy volunteers accepted : No
Gender eligible for study: All
Things to know
Study dates
Study start: 2022-04-30
Primary completion: 2026-05-22
Study completion finish: 2026-05-22
Study type
TREATMENT
Phase
PHASE3
Trial ID
NCT04779320
Intervention or treatment
DRUG: Vedolizumab IV
Conditions
- • Crohn's Disease (CD)
Find a site
Closest Location:
Children's Hospital at Westmead
Research sites nearby
Select from list below to view details:
Children's Hospital at Westmead
Westmead, New South Wales, Australia
Queensland Childrens Hospital
South Brisbane, Queensland, Australia
Monash Health, Monash Medical Centre
Clayton, Victoria, Australia
Royal Children's Hospital Melbourne - PIN
Parkville, Victoria, Australia
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Participant Group/Arm | Intervention/Treatment |
---|---|
EXPERIMENTAL: Induction Period: 10 to 15 kg, Vedolizumab 150 mg
| DRUG: Vedolizumab IV
|
EXPERIMENTAL: Induction Period: >15 to <30 kg, Vedolizumab 200 mg
| DRUG: Vedolizumab IV
|
EXPERIMENTAL: Induction Period: ≥30 kg, Vedolizumab 300 mg
| DRUG: Vedolizumab IV
|
EXPERIMENTAL: Maintenance Period: 10 to 15 kg Vedolizumab 150 mg
| DRUG: Vedolizumab IV
|
EXPERIMENTAL: Maintenance Period: 10 to 15 kg Vedolizumab 100 mg
| DRUG: Vedolizumab IV
|
EXPERIMENTAL: Maintenance Period: >15 to <30 kg, Vedolizumab 200 mg
| DRUG: Vedolizumab IV
|
EXPERIMENTAL: Maintenance Period: >15 to <30 kg Vedolizumab 100 mg
| DRUG: Vedolizumab IV
|
EXPERIMENTAL: Maintenance Period: ≥30 kg, Vedolizumab 300 mg
| DRUG: Vedolizumab IV
|
EXPERIMENTAL: Maintenance Period: ≥30 kg: Vedolizumab 150 mg
| DRUG: Vedolizumab IV
|
What is the study measuring?
Primary outcome
Primary Outcome Measure | Primary Outcome Description | Primary Outcome Time Frame |
---|---|---|
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. | Week 54 |
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. | Week 54 |
Secondary outcome
Secondary Outcome Measure | Secondary Outcome Description | Secondary Outcome Time Frame |
---|---|---|
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. | Week 14 |
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. | Week 54 |
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. | Week 54 |
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. | Week 54 |
Percentage of Participants with Sustained Endoscopic Remission Based on SES-CD Score | Sustained endoscopic remission is where participants achieves endoscopic remission based on SES-CD ≤4 with at least a 2-point reduction from Baseline and no sub-score \>1. The SES-CD evaluates 4 endoscopic variables (Size of ulcers, Ulcerated surface, Affected surface and Presence of narrowing). The score for each endoscopic variable is sum of values obtained for each segment. The SES-CD total is the sum of the four endoscopic variable scores from 0 to 56, where higher scores indicate more severe disease. | Week 14 |
Percentage of Participants with Sustained Endoscopic Remission Based on SES-CD Score | Sustained endoscopic remission is where participants achieves endoscopic remission based on SES-CD ≤4 with at least a 2-point reduction from Baseline and no sub-score \>1. The SES-CD evaluates 4 endoscopic variables (Size of ulcers, Ulcerated surface, Affected surface and Presence of narrowing). The score for each endoscopic variable is sum of values obtained for each segment. The SES-CD total is the sum of the four endoscopic variable scores from 0 to 56, where higher scores indicate more severe disease. | Week 54 |
Percentage of Participants with Sustained Clinical Remission at Week 14 Based on PCDAI Score | Sustained Clinical Remission is where participants will achieve clinical remission based on PCDAI at Weeks 14 and 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 will range from 0 to 100, with higher scores indicating more active disease. | Week 14 |
Percentage of Participants with Sustained Clinical Remission at Week 54 Based on PCDAI Score | Sustained Clinical Remission is where participants will achieve clinical remission based on PCDAI at Weeks 14 and 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 will range from 0 to 100, with higher scores indicating more active disease. | Week 54 |
Serum Trough Concentrations of Vedolizumab Over Time | Not Specified | Predose and postdose at multiple time points (up to 54 weeks) |
Percentage of Participants With Positive Antivedolizumab Antibodies | Not Specified | Pre-dose (up to 54 weeks) |
Percentage of Participants With Positive Neutralizing Antivedolizumab Antibody Titers | Not Specified | Pre-dose (up to 54 weeks) |
Sustained Clinical Response at Week 14 Based on PCDAI Score | Sustained clinical response is where a participant achieve clinical response based on PCDAI score ≤30 and reduction of the PCDAI by ≥15 points from Baseline. 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 will range from 0 to 100, with higher scores indicating more active disease. | Week 14 |
Sustained Clinical Response at Week 54 Based on PCDAI Score | Sustained clinical response is where a participant achieve clinical response based on PCDAI score ≤30 and reduction of the PCDAI by ≥15 points from Baseline. 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 will range from 0 to 100, with higher scores indicating more active disease. | Week 54 |
Percentage of Participants with Clinical Remission at Weeks 2, 6, 10, 14, 22, 30, 38, 46, and 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: HCT (adjusted for age and sex), ESR, and albumin level. The PCDAI score will range from 0 to 100, with higher scores indicating more active disease. | Weeks 2, 6, 10, 14, 22, 30, 38, 46, and 54 |
Percentage of Participants with Change in Baseline in Clinical Response at Weeks 2, 6, 10, 14, 22, 30, 38, 46, and 54 | Clinical Response is where participants achieves clinical response if PCDAI ≤30 with reduction in the PCDAI of ≥15 points from Baseline. 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 will range from 0 to 100, with higher scores indicating more active disease. | Baseline, weeks 2, 6, 10, 14, 22, 30, 38, 46, and 54 |
Percentage of Participants with at Least One Adverse Event (AE), Serious Adverse Event (SAE), and AE of special interest (AESI) | An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have causal relationship with this treatment. AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a drug whether it is considered related to drug. SAE is any untoward medical occurrence that at any dose: results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, leads to congenital anomaly/birth defect and/or is important medical event. An AESI (serious or non-serious) is one of scientific and medical concern specific to compound or program, for which ongoing monitoring and rapid communication by investigator. AESIs include- opportunistic infection, such as progressive multifocal leukoencephalopathy (PML), liver injury, malignancies, infusion-related reactions, hypersensitivity. | From first dose of study drug before each dose on dosing days through the Week 72 |
Change from Baseline in Weight | Change from in Baseline in weight will be calculated as: Weight at each study visit (up to Week 54) - Weight at Baseline. | Baseline up to Week 54 |
Change from Baseline in Linear Growth Z-score | Linear growth Z-score will be calculated as: Z-score = (observed value - median value of the reference population)/ standard deviation value of reference population. | Baseline up to Week 54 |
Change from Baseline in Tanner Stages at Week 54 | Tanner Stage is used to define physical measurements of sexual development based on external primary and secondary sex characteristics. Female and male participants are evaluated for breast development and genital development respectively and both genders for pubic hair distribution based on a 5-stage scale ranging from Stage I (prepubertal/preadolescent characteristics) to Stage V (mature or adult characteristics). | Week 54 |
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