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NCT04779320PHASE3Recruiting

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

Takeda

Start Date

2/10/2022

Completion Date

9/13/2027

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 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.

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 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

Age Range: 2 years to 17 years

Main Inclusion Criteria: 1. The participants has moderately to severely active CD, unresponsive or intolerant to their current standard of care (SOC). 2. The participants weigh ≥10 kg at the time of screening and enrollment into the study. 3. Participants with Crohn's disease (CD) diagnosed at least 1 month before screening. Participants with moderately to severely active CD defined by a Pediatric Crohn's Disease Activity Index (PCDAI) \>30 and an simple endoscopic score for Crohn's Disease (SES-CD) \>6 (or an SES-CD ≥4 if disease is confined to terminal ileum) at screening endoscopy. 4. Participants who have failed, lost response to, or been intolerant to treatment with at least 1 of the following agents: corticosteroids, immunomodulators (eg, azathioprine (AZA), 6-mercaptopurine (6-MP), methotrexate \[MTX\]), and/or tumor necrosis factor (TNF)-α antagonist therapy (eg, infliximab, adalimumab). This includes participants who are dependent on corticosteroids or exclusive or partial enteral nutrition to control symptoms and who are experiencing worsening of disease in the moderate-to-severe range when attempting to wean off corticosteroids or discontinue exclusive enteral nutrition. 5. Participants with extensive colitis or pancolitis of \>8 years' duration or left-sided colitis of \>12 years' duration must have documented evidence of a negative surveillance colonoscopy within 12 months before screening. 6. Participants with vaccinations that are up-to-date based on the countrywide accepted schedule of childhood vaccines. Main Exclusion Criteria: 1. Participants who have received either (1) an investigational biologic (other than those listed in Exclusion Criterion #1) within 60 days or 5 half-lives before screening (whichever is longer); or (2) an approved biologic or biosimilar agent within 2 weeks before the first dose of study drug or at any time during the screening period. 2. Participants with active cerebral/meningeal disease, signs/symptoms or history of progressive multifocal leukoencephalopathy (PML) or any other major neurological disorders including stroke, multiple sclerosis, brain tumor or neurodegenerative disease. 3. The participants had a clinically significant infection (eg, pneumonia, pyelonephritis, coronavirus disease 2019 \[COVID-19\]) within 30 days prior to first dose of study drug. 4. The participants has received any live vaccinations within 30 days prior to first dose. 5. Participants who currently require surgical intervention or are anticipated to require surgical intervention for CD during this study. 6. Participants who have had subtotal or total colectomy or have a jejunostomy, ileostomy, colostomy, ileo-anal pouch, known fixed stenosis of the intestine, short bowel syndrome, or \>3 small intestine resections. 7. Participants with a current diagnosis of indeterminate colitis. 8. Participants with clinical features suggesting monogenic very early-onset inflammatory bowel disease. 9. Active or latent tuberculosis (TB), as evidenced by a diagnostic TB test performed within 30 days of screening or during the screening Period that is positive, defined as: * Positive QuantiFERON test or 2 successive indeterminate QuantiFERON tests, OR * A TB skin test reaction ≥5 mm. 10. Participants with evidence of positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb). Hepatitis B virus (HBV) immune participants(i.e., hepatitis B surface antigen \[HBsAg\]-negative and hepatitis B antibody-positive) may, however, be included. Note: If a participant tests negative for HBsAg, but positive for HBcAb, the participant would be considered eligible if the absence of HBV DNA is confirmed by HBV DNA polymerase chain reaction reflex testing performed in the central laboratory. 11. Participants with chronic hepatitis C virus (HCV) (ie, positive HCV antibody \[HCVAb\] and HCV RNA). Note: Participants who are HCVAb-positive without evidence of HCV RNA may be considered eligible (spontaneous viral clearance or previously treated and cured \[defined as no evidence of HCV RNA at least 12 weeks before baseline\]). 12. The participants has any identified congenital or acquired immunodeficiency (eg, common variable immunodeficiency, human immunodeficiency virus \[HIV\] infection, organ transplantation). 13. The participant has evidence of dysplasia or history of malignancy other than a successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma or localized carcinoma in situ of the cervix. 14. Participants with positive stool studies for ova and/or parasites or stool culture at screening visit. 15. Participants with positive Clostridioides difficile (C difficile) stool test at screening visit. Other inclusion/exclusion criteria may apply.

Interventions

DRUG

Vedolizumab IV

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Conditions

Crohn's Disease (CD)

Locations

Phoenix Childrens Hospital

Phoenix, Arizona 85016

United States

Cedars Sinai Medical Center

Los Angeles, California 90048

United States

Rady Childrens Hospital San Diego - PIN

San Diego, California 92123

United States

University of California San Francisco

San Francisco, California 94143

United States

I.H.S Health LLC

Kissimmee, Florida 34741

United States

Childrens Center For Digestive Healthcare

Atlanta, Georgia 30342

United States

Advocate Children's Hospital Park Ridge

Park Ridge, Illinois 60068

United States

Riley Hospital For Children

Indianapolis, Indiana 46202

United States

Johns Hopkins University

Baltimore, Maryland 21287

United States

Boston Children's Hospital

Boston, Massachusetts 02115

United States

MNGI Digestive Health, PA

Minneapolis, Minnesota 55413

United States

Mayo Clinic - PIN

Rochester, Minnesota 55905

United States

Goryeb Children's Hospital

Morristown, New Jersey 07960

United States

The Steven and Alexandra Cohen Childrens Medical Center of New York - BRANY - PPDS

New Hyde Park, New York 11042

United States

University of Rochester Medical Center PPDS

Rochester, New York 14642

United States

Stony Brook University Medical Center

Stony Brook, New York 11794

United States

SUNY Upstate Medical Center

Syracuse, New York 13202

United States

University Hospitals Cleveland Medical Center

Cleveland, Ohio 44106

United States

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania 15201

United States

Hasbro Children's Hospital

Providence, Rhode Island 02903

United States

Texas Children's Hospital

Houston, Texas 77030

United States

Carilion Children's Tanglewood Center

Roanoke, Virginia 24018

United States

Children's Hospital at Westmead

Westmead, New South Wales 2145

Australia

Queensland Childrens Hospital

South Brisbane, Queensland 4101

Australia

Monash Health, Monash Medical Centre

Clayton, Victoria 3168

Australia

Royal Children's Hospital Melbourne - PIN

Parkville, Victoria 3052

Australia

UZ Antwerpen

Edegem, Antwerpen 2650

Belgium

Universitair Ziekenhuis Brussel - PIN

Jette, Brussels Capital 1090

Belgium

UZ Leuven

Leuven, Vlaams Brabant 3000

Belgium

University of Alberta Hospital

Edmonton, Alberta AB T6G 2B7

Canada

British Columbia Children's Hospital

Vancouver, British Columbia V6H3V4

Canada

London Health Sciences Centre

London, Ontario N6A 4G5

Canada

Centre Hospitalier Universitaire Sainte-Justine

Montreal, Quebec

Canada

Beijing Children Hospital,Capital Medical University

Beijing, Beijing Municipality 100045

China

Henan Children's Hospital(Zhengzhou Children's Hospital)

Zhengzhou, Henan 450000

China

Children's Hospital of Fudan University

Shanghai, Shanghai Municipality 201102

China

The Children's Hospital Zhejiang UniversitySchool of Medicine

Hangzhou, Zhejiang 310003

China

Klinika Za Djecje Bolesti Zagreb

Zagreb, City of Zagreb 10000

Croatia

University Hospital Center Zagreb

Zagreb, City of Zagreb 10000

Croatia

University Hospital Centre Split

Split, 21000

Croatia

Fakultni nemocnice Kralovske Vinohrady

Prague, Praha, Hlavni Mesto 100 34

Czechia

Fakultni Thomayerova Nemocnice

Prague, Praha, Hlavni Mesto 140 00

Czechia

Fakultni nemocnice Ostrava

Ostrava,

Czechia

Attikon University General Hospital

Athens, Attica 124 62

Greece

Children's Hospital "Agia Sofia"

Athens,

Greece

Ippokratio General Hospital of Thessaloniki

Thessaloniki, 564 29

Greece

Ippokratio General Hospital of Thessaloniki

Thessaloniki, 564 29

Greece

Borsod-Abauj-Zemplen Megyei Kozponti Korhaz es Egyetemi Oktato Korhaz

Miskolc, Borsod-Abauj Zemplen county 3526

Hungary

Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont

Szeged, Csongrád megye 6720

Hungary

Semmelweis Egyetem

Budapest, 1083

Hungary

Schneider Childrens Medical Center of Israel Petah Tikvah PIN

Petah Tikva, Central District 49202

Israel

Tel Aviv Sourasky Medical Center PPDS

Jerusalem, Jerusalem 90000

Israel

Soroka University Medical Centre

Beersheba, 84101

Israel

Rambam Medical Center - PPDS

Haifa, 31096

Israel

Carmel Medical Center

Haifa, 34362

Israel

Shaare Zedek Medical Center

Jerusalem, 91031

Israel

Hadassah Medical Center - PPDS

Jerusalem, 91120

Israel

AOU dell'Universita degli Studi della Campania Luigi Vanvitelli

Naples, Campania 80131

Italy

Azienda Ospedaliera Universitaria Federico II

Naples, Campania 80131

Italy

Azienda USL di Bologna

Bologna, Emilia-Romagna 40133

Italy

Sapienza University of Rome

Rome, Lazio 161

Italy

ASST di Monza - Azienda Ospedaliera San Gerardo

Monza, Lombardy 20900

Italy

Universita degli Studi di Padova

Padova, Veneto 35122

Italy

Kurume University Hospital

Kurume-Shi, Hukuoka 830-0011

Japan

Japanese Red Cross Kumamoto Hospital

Kumamoto, Kumamoto 861-8520

Japan

Juntendo University Hospital

Bunkyo-Ku, Tokyo 113-8431

Japan

National Center for Child Health and Development

Setagaya-Ku, Tokyo 157-8535

Japan

Hospital of Lithuanian University of Health Sciences Kaunas Clinics

Kaunas, Kaunas County LT-50161

Lithuania

Vilnius University Hospital Santaros Klinikos

Vilnius, Vilnius County 8406

Lithuania

Uniwersytecki Szpital Dzieciecy

Krakow, Lesser Poland Voivodeship 30-663

Poland

Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu

Wroclaw, Lower Silesian Voivodeship 50-369

Poland

WIP Warsaw IBD Point Profesor Kierkus

Warsaw, Masovian Voivodeship 00-728

Poland

Instytut Pomnik Centrum Zdrowia Dziecka

Warsaw, Masovian Voivodeship 04-736

Poland

Korczowski Bartosz, Gabinet Lekarski

Rzeszów, Podkarpackie Voivodeship 35-302

Poland

Copernicus Podmiot Leczniczy Sp. z o.o.

Gdansk, Pomeranian Voivodeship 80-803

Poland

Gornoslaskie Centrum Zdrowia Dziecka Im. Sw. Jana Pawla II Spsk Nr 6 Sum W Katowicach

Katowice, Silesian Voivodeship 40-752

Poland

Twoja Przychodnia SCM

Szczecin, West Pomeranian Voivodeship 71-434

Poland

SPZOZ Centralny Szpital Kliniczny UM w Lodzi

Lodz, 91-738

Poland

Instytut Centrum Zdrowia Matki Polki

Lodz, Łódź Voivodeship 93-338

Poland

Detska fakultna nemocnica s poliklinikou Banska Bystrica

Banská Bystrica, 974 09

Slovakia

Narodny ustav detskych chorob

Bratislava, 833 40

Slovakia

Kyungpook National University Chilgok hospital

Daegu, Daegu Gwang'yeogsi 41404

South Korea

Gachon University Gil Medical Center

Incheon, Incheon Gwang'yeogsi 21565

South Korea

Seoul National University Hospital

Seongnam, Seoul

South Korea

Samsung Medical Center - PPDS

Seoul, 6351

South Korea

Hospital Sant Joan de Deu - PIN

Esplugues de Llobregat, Barcelona 8950

Spain

Hospital de Sagunto

Sagunto, Valencia 46520

Spain

Hospital Infantil Universitario Nino Jesus - PIN

Madrid, 28009

Spain

Hospital Regional Universitario de Malaga - Hospital Materno Infantil

Málaga, 29011

Spain

Hospital Universitario Virgen del Rocio - PPDS

Seville, 41013

Spain

Kings College Hospital

London, London, City of SE5 9RS

United Kingdom

Great Ormond Street Hospital (GOSH)

London, London, City of WC1N 3AJ

United Kingdom

Noahs Ark Childrens Hospital for Wales - PPDS - PIN

Cardiff, South Glamorgan CF14 4XW

United Kingdom

Birmingham Children's Hospital NHS Foundation Trust

Birmingham, West Midlands B4 6NH

United Kingdom

Barts Health NHS Trust

London, E1 1BB

United Kingdom

Royal Manchester Children's Hospital - PPDS

Manchester, M27 4HA

United Kingdom