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A Study of Vedolizumab in Children and Teenagers With Moderate to Severe Ulcerative Colitis (UC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04779307
Recruitment Status : Recruiting
First Posted : March 3, 2021
Last Update Posted : June 3, 2022
Sponsor:
Information provided by (Responsible Party):
Takeda

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.

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.


Condition or disease Intervention/treatment Phase
Colitis, Ulcerative Drug: Vedolizumab Phase 3

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 CD including exclusive and/or partial enteral nutrition therapy, immunomodulators (eg, 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:

  • 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 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 group. 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)
  • Participants ≥30 kg, Vedolizumab 150 mg (Low dose)
  • Participants >15 to <30 kg, Vedolizumab 200 mg (High dose)
  • Participants >15 to <30 kg, Vedolizumab 100 mg (Low dose)
  • Participants 10 to 15 kg, Vedolizumab 150 mg (High dose)
  • Participants 10 to 15 kg, Vedolizumab 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 based on the weight at the time of the worsening of disease. In addition one-time rescue therapy with corticosteroids is allowed.

This multi-center trial will be conducted worldwide. After the Week 54, participants may be eligible to participate in extension study. Participants who do not roll over in the extension study will undergo a safety visit 18 weeks after the last dose of vedolizumab followed by 2 years of long term follow-up (up to 104 weeks). During this period a safety survey by telephone will be performed every 6 months for 2 years after the last dose of study drug.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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 Ulcerative Colitis Who Achieved Clinical Response Following Open-Label Vedolizumab Intravenous Therapy
Actual Study Start Date : October 19, 2021
Estimated Primary Completion Date : May 30, 2024
Estimated Study Completion Date : May 30, 2024

Resource links provided by the National Library of Medicine

Drug Information available for: Vedolizumab

Arm Intervention/treatment
Experimental: Induction Period: Participants ≥30 kg, Vedolizumab 300 mg
Vedolizumab 300 mg, intravenous (IV) infusion, at Day 1, Weeks 2 and 6 in the Induction Period. Participants with UC having Baseline weight of ≥30 kg were included in this arm.
Drug: Vedolizumab
Vedolizumab IV infusion.
Other Names:
  • MLN0002
  • ENTYVIO
  • KYNTELES

Experimental: Induction Period: Participants >15 to <30 kg, Vedolizumab 200 mg
Vedolizumab 200 mg, IV infusion, at Day 1, Weeks 2 and 6 in the Induction Period. Participants with UC having Baseline weight of >15 to <30 kg were included in this arm.
Drug: Vedolizumab
Vedolizumab IV infusion.
Other Names:
  • MLN0002
  • ENTYVIO
  • KYNTELES

Experimental: Induction Period: Participants 10 to 15 kg, Vedolizumab 150 mg
Vedolizumab 150 mg, IV infusion, at Day 1, Weeks 2 and 6 in the Induction Period. Participants with UC having Baseline weight of 10 to 15 kg were included in this arm.
Drug: Vedolizumab
Vedolizumab IV infusion.
Other Names:
  • MLN0002
  • ENTYVIO
  • KYNTELES

Experimental: Maintenance Period: Participants ≥30 kg, Vedolizumab 300 mg
Vedolizumab 300 mg, IV infusion, once every 8 weeks (Q8W) from Week 14 up to Week 46 in the Maintenance Period. Participants with Week 14 weight of ≥30 kg who achieved clinical response at Week 14 randomized to this high dose arm group will receive vedolizumab 300 mg.
Drug: Vedolizumab
Vedolizumab IV infusion.
Other Names:
  • MLN0002
  • ENTYVIO
  • KYNTELES

Experimental: Maintenance Period: Participants ≥30 kg, Vedolizumab 150 mg
Vedolizumab 150 mg, IV infusion, Q8W from Week 14 up to Week 46 in the Maintenance Period. Participants with Week 14 weight of ≥30 kg who achieved clinical response at Week 14 randomized to this low dose arm group will receive vedolizumab 150 mg.
Drug: Vedolizumab
Vedolizumab IV infusion.
Other Names:
  • MLN0002
  • ENTYVIO
  • KYNTELES

Experimental: Maintenance Period: Participants >15 to <30 kg, Vedolizumab 200 mg
Vedolizumab 200 mg, IV infusion, Q8W from Week 14 up to Week 46 in the Maintenance Period. Participants with Week 14 weight of >15 to <30 kg who achieved clinical response at Week 14 randomized to this high dose arm group will receive vedolizumab 200 mg.
Drug: Vedolizumab
Vedolizumab IV infusion.
Other Names:
  • MLN0002
  • ENTYVIO
  • KYNTELES

Experimental: Maintenance Period: Participants >15 to <30 kg, Vedolizumab 100 mg
Vedolizumab 100 mg, IV infusion, Q8W from Week 14 up to Week 46 in the Maintenance Period. Participants with Week 14 weight of >15 to <30 kg who achieved clinical response at Week 14 randomized to this low dose arm group will receive vedolizumab 100 mg.
Drug: Vedolizumab
Vedolizumab IV infusion.
Other Names:
  • MLN0002
  • ENTYVIO
  • KYNTELES

Experimental: Maintenance Period: Participants 10 to 15 kg, Vedolizumab 150 mg
Vedolizumab 150 mg, IV infusion, Q8W from Week 14 up to Week 46 in the Maintenance Period. Participants with Week 14 weight of 10 to 15 kg who achieved clinical response at Week 14 randomized to this high dose arm group will receive vedolizumab 150 mg.
Drug: Vedolizumab
Vedolizumab IV infusion.
Other Names:
  • MLN0002
  • ENTYVIO
  • KYNTELES

Experimental: Maintenance Period: Participants 10 to 15 kg, Vedolizumab 100 mg
Vedolizumab 100 mg, IV infusion, Q8W from Week 14 up to Week 46 in the Maintenance Period. Participants with Week 14 weight of 10 to 15 kg who achieved clinical response at Week 14 randomized to this low dose arm group will receive vedolizumab 100 mg.
Drug: Vedolizumab
Vedolizumab IV infusion.
Other Names:
  • MLN0002
  • ENTYVIO
  • KYNTELES




Primary Outcome Measures :
  1. Percentage of Participants with Clinical Remission at Week 54 Based on Modified Mayo Score [ Time Frame: Week 54 ]
    Clinical remission based on the modified Mayo score is defined as stool frequency subscore 0 to 1 and a decrease of 1 or more from Baseline; rectal bleeding subscore of 0; and, endoscopy subscore 0 to 1 (modified so that a score of 1 does not include friability). Mayo score is an instrument designed to measure disease activity of UC. Modified Mayo score consists of 3 sub-scores: stool frequency, rectal bleeding, and Mayo endoscopic subscore (findings on endoscopy). Each subscale is graded from 0 to 3 with higher scores indicating more severe disease. These scores are summed to give a total score range of 0 to 9. Here, higher score indicates more severe disease.


Secondary Outcome Measures :
  1. Percentage of Participants with Clinical Remission at Week 14 Based on Modified Mayo Score [ Time Frame: Week 14 ]
    Clinical remission based on the modified Mayo score is defined as stool frequency subscore 0 to 1 and a decrease of 1 or more from Baseline; rectal bleeding subscore of 0; and, endoscopy subscore 0 to 1 (modified so that a score of 1 does not include friability). Mayo score is an instrument designed to measure disease activity of UC. Modified Mayo score consists of 3 sub-scores: stool frequency, rectal bleeding, and Mayo endoscopic subscore (findings on endoscopy). Each subscale is graded from 0 to 3 with higher scores indicating more severe disease. These scores are summed to give a total score range of 0 to 9. Here, higher score indicates more severe disease.

  2. Percentage of Participants with Sustained Clinical Remission at Week 54 Based on Modified Mayo Score [ Time Frame: Week 54 ]
    Sustained clinical remission is where a participant achieves clinical remission at Weeks 14 and 54, based on the modified Mayo score. It is defined as stool frequency subscore 0 to 1 and a decrease of 1 or more from Baseline; rectal bleeding subscore of 0; and, endoscopy subscore 0 to 1 (modified so that a score of 1 does not include friability). Mayo score is an instrument designed to measure disease activity of UC. Modified Mayo score consists of 3 sub-scores: stool frequency, rectal bleeding, and Mayo endoscopic subscore (findings on endoscopy). Each subscale is graded from 0 to 3 with higher scores indicating more severe disease. These scores are summed to give a total score range of 0 to 9. Here, higher score indicates more severe disease.

  3. Percentage of Participants with Sustained Endoscopic Remission at Weeks 14 and 54 [ Time Frame: Weeks 14 and 54 ]
    Sustained endoscopic remission was defined as Mayo endoscopic score (MES) of ≤1 point. MES is a subscale of the Mayo score, an instrument designed to measure disease activity of UC. The subscale is 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 scores indicate more severe disease.

  4. Percentage of Participants with Endoscopic Response at Weeks 14 and 54 [ Time Frame: Weeks 14 and 54 ]
    Endoscopic response was defined as a decrease in MES by ≥1 grade. MES is a subscale of the Mayo score, an instrument designed to measure disease activity of UC. The subscale is 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 scores indicate more severe disease.

  5. Percentage of Participants with Corticosteroid-free Clinical Remission at Week 54 [ Time Frame: Week 54 ]
    Corticosteroid-free clinical remission is where a participant achieves corticosteroid-free clinical remission at Week 54, and was off corticosteroids at least 12 weeks prior to and at Week 54. Clinical remission based on the modified Mayo score is defined as stool frequency subscore 0 to 1 and a decrease of 1 or more from Baseline; rectal bleeding subscore of 0; and, endoscopy subscore 0 to 1 (modified so that a score of 1 does not include friability). Mayo score is an instrument designed to measure disease activity of UC. Modified Mayo score consists of 3 sub-scores: stool frequency, rectal bleeding, and Mayo endoscopic subscore (findings on endoscopy). Each subscale is graded from 0 to 3 with higher scores indicating more severe disease. These scores are summed to give a total score range of 0 to 9. Here, higher score indicates more severe disease.

  6. Percentage of Participants with Clinical Remission at Week 54 Based on Complete Mayo Score [ Time Frame: Week 54 ]
    Clinical remission based on the complete Mayo score is where a participant achieved a complete Mayo score ≤2 points with no individual subscore >1 at Week 54. Mayo score is an instrument designed to measure disease activity of UC. Complete Mayo score consists of 4 sub-scores: stool frequency, rectal bleeding, Mayo endoscopic subscore (findings on endoscopy), and Physician's global assessment. Each subscale is graded from 0 to 3 with higher scores indicating more severe disease. These scores are summed to give a total score range of 0 to 12. Here, higher score indicates more severe disease.

  7. Serum Trough Concentrations of Vedolizumab over Time [ Time Frame: Predose and at multiple time points (up to 72 weeks) postdose ]
  8. Percentage of Participants with Positive Anti-vedolizumab Antibodies (AVA) [ Time Frame: Predose and at multiple time points (up to 72 weeks) postdose ]
  9. Percentage of Participants with Positive Neutralizing AVA Titers [ Time Frame: Predose and at multiple time points (up to 72 weeks) postdose ]
  10. Percentage of Participants with Sustained Clinical Response at Weeks 14 and 54 Based on Complete Mayo Score [ Time Frame: Weeks 14 and 54 ]
    Clinical response is where a participant has a reduction in complete Mayo score of ≥3 points and ≥30% from Baseline with an accompanying decrease in rectal bleeding subscore of ≥1 point or absolute rectal bleeding subscore of ≤1 point. Mayo score is an instrument designed to measure disease activity of UC. Complete Mayo score consists of 4 sub-scores: stool frequency, rectal bleeding, Mayo endoscopic subscore (findings on endoscopy), and Physician's global assessment. Each subscale is graded from 0 to 3 with higher scores indicating more severe disease. These scores are summed to give a total score range of 0 to 12. Here, higher score indicates more severe disease.

  11. Percentage of Participants with Clinical Response up to Week 54 Based on Partial Mayo Score [ Time Frame: Weeks 2, 6, 10, 14, 22, 30, 38, 46, and 54 ]
    Clinical response is defined as reduction of ≥2 points and ≥25% from the Baseline partial Mayo score, including a ≥1-point decrease in the Mayo stool frequency subscore and a ≥1-point reduction in the rectal bleeding subscore or absolute rectal bleeding subscore of ≤1 point. Partial Mayo score consists of 3 sub-scores: stool frequency, rectal bleeding, and Physician's global assessment. Each subscale is graded from 0 to 3 with higher scores indicating more severe disease. These scores are summed to give a total score range of 0 to 9. Higher score indicates more severe disease.

  12. Percentage of Participants with at least One Adverse Event (AE), Serious Adverse Event (SAE), and Adverse Event of Special Interest (AESI) [ Time Frame: Up to 158 weeks ]
    An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug which does not necessarily have to have a causal relationship with the treatment. An SAE is defined as 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 a congenital anomaly/birth defect and/or is a important medical event. An AESI (serious or non-serious) is one of scientific and medical concern specific to the compound or program, for which ongoing monitoring and rapid communication by the investigator to Takeda may be appropriate. AESIs include: infusion-related reactions and hypersensitivity, serious infection, malignancy, or other (liver injury and progressive multifocal leukoencephalopathy [PML]).

  13. Change from Baseline in Weight [ Time Frame: Baseline, up to Week 54 ]
    Change from in Baseline in weight will be calculated as: Weight at each study visit (up to Week 54) - Weight at Baseline.

  14. Change from Baseline in Linear Growth Z-score [ Time Frame: Baseline, up to Week 54 ]
    Linear growth Z-score will be calculated as: Z-score = (observed value - median value of the reference population) / standard deviation value of reference population.

  15. Percentage of Participants Achieving Tanner Stage V [ Time Frame: Week 54 ]
    Percentage of participants achieving Tanner Stage V at Week 54 based on progression of pubertal changes from Baseline will be reported. Tanner Stage is used to measure pubertal development. Female (F) and male (M) participants are evaluated for breast development and genital development respectively and both genders for pubic hair development. Tanner Stage is based on progression through 5-stages.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   2 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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. Has moderately to severely active UC diagnosed at least 1 month before screening, defined by 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 1 and mandating a score of at least 2).
  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. Has chronic hepatitis B virus (HBV) infection* or chronic hepatitis C virus infection.

    • HBV immune participants (ie, being hepatitis B surface antigen negative and hepatitis B antibody positive) may be included, however.
  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 Clostridium difficile stool test at screening visit.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04779307


Contacts
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Contact: Takeda Contact +1-877-825-3327 medinfoUS@takeda.com

Locations
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Sponsors and Collaborators
Takeda
Additional Information:
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Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT04779307    
Other Study ID Numbers: MLN0002-3024
2020-004300-34 ( EudraCT Number )
jRCT2071210030 ( Registry Identifier: jRCT )
First Posted: March 3, 2021    Key Record Dates
Last Update Posted: June 3, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
URL: https://vivli.org/ourmember/takeda/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Takeda:
Drug Therapy
Additional relevant MeSH terms:
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Colitis
Colitis, Ulcerative
Ulcer
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Pathologic Processes
Inflammatory Bowel Diseases
Vedolizumab
Gastrointestinal Agents