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

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

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.

Study Overview

• Status: Completed
• Conditions: Colitis, Ulcerative
• Intervention / Treatment: Drug: Vedolizumab

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.

• Study Type: Interventional
• Enrollment (Actual): 121
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Westmead, New South Wales, Australia, 2145
      • Children's Hospital at Westmead
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Queensland Childrens Hospital
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Health, Monash Medical Centre
    • Parkville, Victoria, Australia, 3052
      • Royal Children's Hospital Melbourne - PIN
• Belgium
  • Antwerpen
    • Edegem, Antwerpen, Belgium, 2650
      • UZ Antwerpen
  • Brussels Capital
    • Jette, Brussels Capital, Belgium, 1090
      • Universitair Ziekenhuis Brussel - PIN
  • Vlaams Brabant
    • Leuven, Vlaams Brabant, Belgium, 3000
      • Universitaire Ziekenhuizen(UZ)Leuven-Campus Gasthuisberg
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2S2
      • University of Alberta Hospital
  • British Columbia
    • Vancouver, British Columbia, Canada, V6H 3V4
      • British Columbia Children's Hospital
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • London Health Sciences Centre
• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100045
      • Beijing Children's Hospital, Capital Medical University - PIN
  • Henan
    • Zhengzhou, Henan, China, 450000
      • Henan Children's Hospital Zhengzhou Children's Hospital
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 201102
      • Children's Hospital of Fudan University
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • The Children's Hospital Zhejiang University School of Medicine
• Croatia
  • City of Zagreb
    • Zagreb, City of Zagreb, Croatia, 10000
      • Klinika Za Djecje Bolesti Zagreb
• Greece
  • Thessaloniki, Greece, 546 42
    • Ippokratio General Hospital of Thessaloniki
  • Attica
    • Athens, Attica, Greece, 115 27
      • Children's Hospital "Agia Sofia"
    • Chaïdári, Attica, Greece, 124 62
      • Attikon University General Hospital
• Hungary
  • Budapest, Hungary, 1085
    • Semmelweis Egyetem
  • Budapest, Hungary, 1033
    • Clinexpert Gyogycentrum
  • Miskolc, Hungary, 3526
    • Borsod-Abauj-Zemplen Varmegyei Kozponti Korhaz es Egyetemi Oktatokorhaz
• Israel
  • Haifa, Israel, 3436212
    • Carmel Medical Center
  • Haifa, Israel, 31096
    • Rambam Medical Center - PPDS
  • Petah Tikva, Israel, 49100
    • Schneider Childrens Medical Center of Israel Petah Tikvah PIN
  • Tel Aviv, Israel, 64239
    • Tel Aviv Sourasky Medical Center
  • Jerusalem
    • Jerusalem, Jerusalem, Israel, 91031
      • Shaare Zedek Medical Center
    • Jerusalem, Jerusalem, Israel, 91120
      • Hadassah Medical Center - PPDS
• Italy
  • Naples, Italy, 280138
    • AOU dell'Universita degli Studi della Campania Luigi Vanvitelli - Piazza Luigi Miraglia, 2
  • Campania
    • Naples, Campania, Italy, 80131
      • Azienda Ospedaliera Universitaria Federico II
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40133
      • Azienda USL di Bologna
  • Lazio
    • Rome, Lazio, Italy, 00161
      • Azienda Ospedaliera Universitaria Policlinico Umberto I - Università di Roma La Sapienza
  • Monza E Brianza
    • Monza, Monza E Brianza, Italy, 20900
      • Fondazione IRCCS San Gerardo dei Tintori - ASST di Monza A. O. San Gerardo
  • Tuscany
    • Florence, Tuscany, Italy, 50139
      • Azienda Ospedaliero Universitaria A Meyer - INCIPIT - PIN
• Japan
  • Kumamoto, Japan, 861-8520
    • Japanese Red Cross Kumamoto Hospital
  • Saitama, Japan, 330-8777
    • Saitama Children's Medical Center
  • Hukuoka
    • Kurume, Hukuoka, Japan, 830-0011
      • Kurume University Hospital
  • Tokyo
    • Bunkyo-Ku, Tokyo, Japan, 113-8431
      • Juntendo University Hospital
    • Setagaya-ku, Tokyo, Japan, 157-8535
      • National Center for Child Health and Development
• Poland
  • Lesser Poland Voivodeship
    • Krakow, Lesser Poland Voivodeship, Poland, 30-663
      • Uniwersytecki Szpital Dziecięcy
  • Masovian Voivodeship
    • Warsaw, Masovian Voivodeship, Poland, 00-728
      • WIP Warsaw IBD Point Profesor Kierkus
    • Warsaw, Masovian Voivodeship, Poland, 04-736
      • Instytut 'Pomnik - Centrum Zdrowia Dziecka'
  • Podkarpackie Voivodeship
    • Rzeszów, Podkarpackie Voivodeship, Poland, 35-302
      • Korczowski Bartosz, Gabinet Lekarski
  • Silesian Voivodeship
    • Katowice, Silesian Voivodeship, Poland, 40-752
      • Gornoslaskie Centrum Zdrowia Dziecka Im. Sw. Jana Pawla II Spsk Nr 6 Sum W Katowicach
  • West Pomeranian Voivodeship
    • Szczecin, West Pomeranian Voivodeship, Poland, 71-434
      • Twoja Przychodnia SCM
  • Łódź Voivodeship
    • Lodz, Łódź Voivodeship, Poland, 91-738
      • SPZOZ Centralny Szpital Kliniczny UM w Lodzi - ul. Pomorska 251
    • Lodz, Łódź Voivodeship, Poland, 93-338
      • Instytut Centrum Zdrowia Matki Polki
• South Korea
  • Daegu Gwang'yeogsi
    • Daegu, Daegu Gwang'yeogsi, South Korea, 41404
      • Kyungpook National University Chilgok Hospital
  • Incheon Gwang'yeogsi
    • Seoul, Incheon Gwang'yeogsi, South Korea, 3080
      • Gachon University Gil Medical Center
  • Seoul Teugbyeolsi
    • Seoul, Seoul Teugbyeolsi, South Korea, 06351
      • Samsung Medical Center
    • Seoul, Seoul Teugbyeolsi, South Korea, 21565
      • Seoul National University Hospital
• United Kingdom
  • Cardiff, United Kingdom, CF14 4XW
    • Noahs Ark Childrens Hospital for Wales
  • London, City of
    • London, London, City of, United Kingdom, E1 1BB
      • The Royal London Hospital
    • London, London, City of, United Kingdom, WC1N 3JH
      • Great Ormond Street Hospital
  • West Midlands
    • Birmingham, West Midlands, United Kingdom, B4 6NH
      • Birmingham Women's and Children's NHS Foundation Trust
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016-7710
      • Phoenix Childrens Hospital -1919 E Thompson Rd
  • California
    • San Diego, California, United States, 92123
      • Rady Childrens Hospital San Diego - PIN
  • Georgia
    • Atlanta, Georgia, United States, 30318-4833
      • Childrens Center For Digestive Healthcare
  • Illinois
    • Park Ridge, Illinois, United States, 60068
      • Advocate Children's Hospital Park Ridge
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55413
      • MNGI Digestive Health PA-Plymouth
    • Rochester, Minnesota, United States, 55905-0001
      • Mayo Clinic - PIN
  • New Jersey
    • Morristown, New Jersey, United States, 07960-6136
      • Goryeb Children's Hospital
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224-1334
      • UPMC Children's Hospital of Pittsburgh-120 Lytton Ave
  • Texas
    • Houston, Texas, United States, 77030-2358
      • Texas Childrens Hospital West Campus
  • Virginia
    • Roanoke, Virginia, United States, 24013-2253
      • Carilion Children's Tanglewood Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

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/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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
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 are 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 are 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 are included in this arm.	Drug: Vedolizumab; Vedolizumab IV infusion.; Other Names: MLN0002; ENTYVIO; KYNTELES

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Clinical Remission at Week 54 Based on Modified Mayo Score	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.	At Week 54

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Clinical Remission at Week 14 Based on Modified Mayo Score	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.	At Week 14
Percentage of Participants With Sustained Clinical Remission at Week 54 Based on Modified Mayo Score	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.	At Week 54
Percentage of Participants With Sustained Endoscopic Remission 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.	At Week 54
Percentage of Participants With Endoscopic Response 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.	At Week 14
Percentage of Participants With Endoscopic Response 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.	At Week 54
Percentage of Participants With Corticosteroid-free Clinical Remission 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.	At Week 54
Percentage of Participants With Clinical Remission at Week 54 Based on Complete Mayo Score	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.	At Week 54
Serum Trough Concentrations of Vedolizumab Over Time	Serum trough concentration of vedolizumab was reported.	Predose at Week 14 and post dose at Week 54
Percentage of Participants With Positive Anti-vedolizumab Antibodies (AVA)	AVA positive was defined as a confirmed AVA positive result.	Up to Week 54
Percentage of Participants With Positive Neutralizing AVA	Positive Neutralizing AVA was defined as a positive result in the neutralizing AVA assay at any visit.	Up to Week 54
Percentage of Participants With Sustained Clinical Response at Week 54 Based on Complete Mayo Score	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.	At Week 54
Percentage of Participants With Clinical Response up to Week 54 Based on Partial Mayo Score	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.	At Weeks 2, 6, 10, 14, 22, 30, 38, 46, and 54
Percentage of Participants With Clinical Remission up to Week 54 Based on Partial Mayo Score	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.	At Weeks 2, 6, 10, 14, 22, 30, 38, 46, and 54
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)	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]).	From first dose of study drug up to end of follow up (up to 3.7 years)
Change From Baseline in Weight	Change from baseline in weight was reported.	At Weeks 2, 6, 10, 14, 22, 30, 38, 46, and 54
Change From Baseline in Weight Z-score	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.	At Weeks 2, 6, 10, 14, 22, 30, 38, 46, and 54
Change From Baseline in Height	Change from baseline in height was reported.	At Weeks 2, 6, 10, 14, 22, 30, 38, 46, and 54
Change From Baseline in Linear Growth Z-score	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.	At Weeks 2, 6, 10, 14, 22, 30, 38, 46, and 54
Number of Participants With Change From Baseline in Tanner Stage 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.	At Week 54

Collaborators and Investigators

• Sponsor: Takeda

Publications and helpful links

Helpful Links

• Click here for more information about this trial in easy-to-understand language, including a Plain Language Summary of the results if the trial has been completed.

Study record dates

Study Major Dates

• Study Start (Actual): October 19, 2021
• Primary Completion (Actual): July 1, 2025
• Study Completion (Actual): July 1, 2025

Study Registration Dates

• First Submitted: March 1, 2021
• First Submitted That Met QC Criteria: March 1, 2021
• First Posted (Actual): March 3, 2021

Study Record Updates

• Last Update Posted (Actual): April 30, 2026
• Last Update Submitted That Met QC Criteria: April 9, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Drug Therapy
• Additional Relevant MeSH Terms: Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Colitis; Colitis, Ulcerative; Gastrointestinal Agents; vedolizumab
• Other Study ID Numbers: MLN0002-3024; 2020-004300-34 (EudraCT Number); jRCT2071210030 (Registry Identifier: jRCT); 2023-509018-12-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• 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