Vedolizumab IV in Pediatric Participants With Ulcerative Colitis (UC) or Crohn's Disease (CD)

NCT ID: NCT03138655

Last Updated: 2020-12-21

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

89 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-11-08

Study Completion Date

2020-05-26

Brief Summary

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The purpose of this study is to evaluate vedolizumab pharmacokinetics (PK), safety and tolerability in pediatric participants with moderately to severely active UC or CD.

Detailed Description

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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 or CD. This study will look at the PK, efficacy, immunogenicity, safety, and tolerability in participants who take vedolizumab.

The study will enroll approximately 80 participants. Participants will be randomly assigned (by chance, like flipping a coin) to one of the two dose regimens (high or low) per weight group \>=30 kg and 10 kg to \<30 kg in ratio 1:1-which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need):

* Vedolizumab high dose group - Vedolizumab 300 mg or 200 mg
* Vedolizumab low dose group - Vedolizumab 150 mg or 100 mg

All participants will be administered vedolizumab via IV infusion. Participants assigned to the low dose group who do not achieve clinical response (based on pediatric UC/CDAI) at Week 14 will receive the high dose (that is, 300 mg for participants \>=30 kg baseline weight and 200 mg for participants 10 kg to \<30 kg baseline weight) of vedolizumab IV at Week 14. Participants assigned to the high dose group who had not achieved clinical response continued on the same blinded high dose at Week 14.

This multi-center trial will be conducted worldwide. The overall time to participate in this study is up to 36 weeks. After completing the Week 22 Visit procedures, eligible participants may enter a blinded extension study. Participants will make multiple visits to the clinic, and those who do not enter extension study will have a final visit 18 weeks after last dose of study drug for a follow-up assessment. Participants who do not enter the extension study will also participate in a long-term safety follow-up, by telephone, 6 months after the last dose of study drug.

Conditions

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Ulcerative Colitis Crohn's Disease

Keywords

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Drug therapy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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UC: <30 kg Participants, Vedolizumab 100 mg

Participants with UC having baseline weight of \<30 kg were randomized to this low dose group and received vedolizumab 100 mg IV infusion on Day 1 and at Weeks 2, 6 and 14.

Group Type EXPERIMENTAL

Vedolizumab

Intervention Type DRUG

Vedolizumab IV infusion.

UC: <30 kg Participants, Vedolizumab 200 mg

Participants with UC having baseline weight of \<30 kg were randomized to this high dose group and received vedolizumab 200 mg IV infusion on Day 1 and at Weeks 2, 6 and 14.

Group Type EXPERIMENTAL

Vedolizumab

Intervention Type DRUG

Vedolizumab IV infusion.

CD: <30 kg Participants, Vedolizumab 100 mg

Participants with CD having baseline weight of \<30 kg were randomized to this low dose group and received vedolizumab 100 mg IV infusion on Day 1 and at Weeks 2, 6 and 14.

Group Type EXPERIMENTAL

Vedolizumab

Intervention Type DRUG

Vedolizumab IV infusion.

CD: <30 kg Participants, Vedolizumab 200 mg

Participants with CD having baseline weight of \<30 kg were randomized to this high dose group and received vedolizumab 200 mg IV infusion on Day 1 and at Weeks 2, 6 and 14.

Group Type EXPERIMENTAL

Vedolizumab

Intervention Type DRUG

Vedolizumab IV infusion.

UC: >=30 kg Participants, Vedolizumab 150 mg

Participants with UC having baseline weight of \>=30 kg were randomized to this low dose group and received vedolizumab 150 mg IV infusion on Day 1 and at Weeks 2, 6 and 14.

Group Type EXPERIMENTAL

Vedolizumab

Intervention Type DRUG

Vedolizumab IV infusion.

UC: >=30 kg Participants, Vedolizumab 300 mg

Participants with UC having baseline weight of \>=30 kg were randomized to this high dose group and received vedolizumab 300 mg IV infusion on Day 1 and at Weeks 2, 6 and 14.

Group Type EXPERIMENTAL

Vedolizumab

Intervention Type DRUG

Vedolizumab IV infusion.

CD: >=30 kg Participants, Vedolizumab 150 mg

Participants with CD having baseline weight of \>=30 kg were randomized to this low dose group and received vedolizumab 150 mg IV infusion on Day 1 and at Weeks 2, 6 and 14.

Group Type EXPERIMENTAL

Vedolizumab

Intervention Type DRUG

Vedolizumab IV infusion.

CD: >=30 kg Participants, Vedolizumab 300 mg

Participants with CD having baseline weight of \>=30 kg were randomized to this low dose group and received vedolizumab 300 mg IV infusion on Day 1 and at Weeks 2, 6 and 14.

Group Type EXPERIMENTAL

Vedolizumab

Intervention Type DRUG

Vedolizumab IV infusion.

Interventions

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Vedolizumab

Vedolizumab IV infusion.

Intervention Type DRUG

Other Intervention Names

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MLN0002 ENTYVIO KYNTELES

Eligibility Criteria

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Inclusion Criteria

1. Participants weighs \>=10 kg at the time of randomization.
2. Has a medical history of moderately to severely active UC during Screening defined as complete Mayo score of 6 to 12, and a total Mayo subscores of stool frequency and rectal bleeding \>=4 and Mayo endoscopy subscore \>=2, or has moderately to severely active CD defined as simple endoscopic score for Crohn's disease (SES-CD) \>=7, and the CDAI components of average daily abdominal pain score of greater than (\>) 1 for the 7 days prior, and total number of liquid/very soft stools \>10 within 7 days prior to first dose of study drug.
3. Has evidence of UC extending proximal to the rectum (that is, not limited to proctitis) or evidence of CD involving the ileum and/or colon, at a minimum.
4. Has extensive colitis or pancolitis of \>8 years duration or left-sided colitis of \>12 years duration must have documented evidence that a surveillance colonoscopy was performed within 12 months prior to their first dose of study drug.
5. Has a family history of colorectal cancer (that is, first-degree relative), personal history of increased colorectal cancer risk, or other known risk factor must be up-to-date on colorectal cancer surveillance.
6. The participant's vaccinations are up to date.
7. Has demonstrated an inadequate response to, loss of response to, or intolerance of at least 1 of the following agents as defined below:

Corticosteroids:

• Signs and/or symptoms of persistently active disease despite a history of at least one 4-week induction regimen that included a dose equivalent to or more than prednisone 1 milligram per kilogram (mg/kg) daily orally for 2 weeks or IV for 1 week.

OR

• Two failed attempts to taper corticosteroids to below a dose equivalent to prednisone 10 mg daily orally on 2 separate occasions.

OR

• History of significant intolerance to corticosteroids (including, but not limited to, Cushing's syndrome, osteopenia/osteoporosis, hyperglycemia, insomnia, and infection).

Immunomodulators:

• Signs and symptoms of persistently active disease despite a history of at least one 8-week regimen of oral azathioprine (AZA) (\>=1.5 milligram per kilogram per day \[mg/kg/day\]) or 6-mercaptopurine (6-MP) mg/kg (\>=1.0 mg/kg/day) or methotrexate (MTX) (\>=10 milligram per square meter \[mg/m\^2\] once a week).

OR

• History of intolerance of at least 1 immunomodulator (including, but not limited to, nausea/vomiting, abdominal pain, pancreatitis, liver function test (LFT) abnormalities, lymphopenia, thiopurine methyltransferase genetic mutation, infection).

Tumor necrosis factor-alpha (TNF-α) antagonists:

• Signs and symptoms of persistently active disease despite a history of at least 1 induction regimen of infliximab 5 mg/kg IV at Week 0 and Weeks 2 and 6 or adalimumab 2-week regimen of 160 mg on Day 1 and 80 mg on Day 15 if \>=40 kg or 80 mg on Day 1 and 40 mg on Day 15 if \<40 kg. For any other TNF-α antagonist, the participant must demonstrate signs and symptoms of persistently active disease despite a history of at least 1 induction regimen, as determined by the investigator.

OR

• Recurrence of symptoms during maintenance dosing following prior clinical benefit, that is, fitting clinically with secondary loss of response (discontinuation despite clinical benefit does not qualify).

OR

• History of intolerance of infliximab or adalimumab (including, but not limited to, infusion-related reaction, demyelination, congestive heart failure, infection).
8. The participant may be receiving a therapeutic dose of the following drugs:

1. Oral 5-aminosalicylic acid (5-ASA) compounds, providing the dose has been stable for the 2 weeks prior to first dose of study drug.
2. Oral corticosteroid therapy (prednisolone at a stable dose \<=50 mg/day, or equivalent steroid), provided that the dose has been stable for the 4 weeks prior to first dose of study drug if corticosteroids have been initiated, or for the 2 weeks prior to first dose of study drug if corticosteroids are being tapered.
3. Probiotics (example, Saccharomyces boulardii), provided the dose has been stable for the 2 weeks prior to first dose of study drug.
4. Antidiarrheals (example, loperamide, diphenoxylate with atropine) for control of chronic diarrhea.
5. Antibiotics used for the treatment of CD (example, ciprofloxacin, metronidazole), providing the dose has been stable for the 2 weeks prior to first dose of study drug.
6. Azathioprine or 6-MP, provided the dose has been stable for the 8 weeks prior to first dose of study drug.
7. Methotrexate (MTX), provided the dose has been stable for the 8 weeks prior to first dose of study drug.

Exclusion Criteria

1. Has had previous exposure to approved or investigational anti-integrins (example, natalizumab, efalizumab, etrolizumab, or AMG 181) or MAdCAM-1 antagonists, or rituximab.
2. Has had prior exposure to vedolizumab.
3. Has a positive progressive multifocal leukoencephalopathy (PML) subjective symptom checklist prior to the administration of the first dose of study drug.
4. Requires surgical intervention for UC or CD, or is anticipated to require surgical intervention for UC or CD during this study.
5. Use of topical (rectal) treatment with 5-ASA or corticosteroid enemas/suppositories within 2 weeks of the administration of the first dose of study drug.
6. Has any unstable or uncontrolled cardiovascular, heart failure moderate to severe (New York Class Association III or IV), pulmonary, hepatic, renal, gastrointestinal (GI), genitourinary, hematological, coagulation, immunological, endocrine/metabolic, neurological, or other medical disorder that, in the opinion of the investigator, would confound the study results or compromise participant safety.
7. 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 millimeter (mm). Participants with documented previously treated TB with a negative QuantiFERON test can be included in the study.
8. Clinically significant current or recent history (within 1 year prior to enrollment) of alcohol dependence or illicit drug use.
9. Has a current diagnosis of indeterminate colitis (Inflammatory bowel disease unclassified \[IBDU\]). For participants less than 6 years of age, any findings that suggest monogenic very early onset inflammatory bowel disease should be excluded.
10. Has evidence of abdominal abscess or toxic megacolon at the initial Screening Visit.
11. Has ileostomy, colostomy, ileo-anal pouch, or known fixed symptomatic stenosis of the intestine.
12. Has extensive colonic resection, example, subtotal or total colectomy.
13. Has a history or evidence of adenomatous colonic polyps that have not been removed.
14. Has a history or evidence of colonic mucosal dysplasia.
15. Has chronic hepatitis B virus (HBV) infection\* or chronic hepatitis C virus (HCV) infection. \* HBV immune participants (that is, being hepatitis B surface antigen \[HBsAg\] negative and hepatitis B antibody positive) may be included, however.
16. Has any identified congenital or acquired immunodeficiency (example, common variable immunodeficiency, human immunodeficiency virus \[HIV\] infection, organ transplantation).
17. Has evidence of or treatment for Clostridium difficile (C difficile) infection within 60 days or other intestinal pathogen within 30 days prior to first dose of study drug.
18. Has any history of malignancy, except for the following: (a) adequately treated nonmetastatic basal cell skin cancer; (b) squamous cell skin cancer that has been adequately treated and that has not recurred for at least 1 year prior to enrollment; and (c) history of cervical carcinoma in situ that has been adequately treated and that has not recurred for at least 3 years prior to first dose of study drug. Participants with remote history of malignancy (example, \>10 years since completion of curative therapy without recurrence) will be considered based on the nature of the malignancy and the therapy received, and inclusion must be discussed with the sponsor on a case-by-case basis prior to enrollment.
19. Has a history of any major neurological disorders, including stroke, multiple sclerosis, brain tumor, or neurodegenerative disease.
20. Has history of lupus.
21. Has had a surgical procedure requiring general anesthesia within 30 days prior to screening or is planning to undergo major surgery during the study period.
Minimum Eligible Age

2 Years

Maximum Eligible Age

17 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Takeda Development Center Americas, Inc.

INDUSTRY

Sponsor Role collaborator

Takeda

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Monitor Clinical Science

Role: STUDY_DIRECTOR

Takeda

Locations

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Cedars-Sinai Medical Center

Los Angeles, California, United States

Site Status

Children's Hospital of Orange County

Orange, California, United States

Site Status

University of California San Francisco

San Francisco, California, United States

Site Status

Connecticut Children's Medical Center

Hartford, Connecticut, United States

Site Status

Nemours Children's Clinic

Wilmington, Delaware, United States

Site Status

Nemours Childrens Specialty Care - Jacksonville

Jacksonville, Florida, United States

Site Status

Nicklaus Children's Hospital

Miami, Florida, United States

Site Status

Children's Center for Digestive Healthcare

Atlanta, Georgia, United States

Site Status

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, United States

Site Status

Indiana University School of Medicine - Indianapolis

Indianapolis, Indiana, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Boston Children's Hospital

Boston, Massachusetts, United States

Site Status

Mayo Clinic - Rochester

Rochester, Minnesota, United States

Site Status

Washington University in St. Louis

St Louis, Missouri, United States

Site Status

Northwell Health

Lake Success, New York, United States

Site Status

Mount Sinai Medical Center

New York, New York, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

The Children's Hospital at Montefiore

The Bronx, New York, United States

Site Status

University Hospitals Rainbow Babies & Children's Hospital

Cleveland, Ohio, United States

Site Status

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Childrens Medical Center of Dallas

Dallas, Texas, United States

Site Status

Texas Children's Hospital

Houston, Texas, United States

Site Status

University of Utah

Salt Lake City, Utah, United States

Site Status

Children's Specialty Group - Medical Center Location

Norfolk, Virginia, United States

Site Status

Seattle Children's Hospital

Seattle, Washington, United States

Site Status

Hopital Universitaire des Enfants Reine Fabiola

Brussels, Brussels Capital, Belgium

Site Status

Universitair Ziekenhuis Brussel

Brussels, Brussels Capital, Belgium

Site Status

Universitair Ziekenhuis Leuven

Leuven, Flemish Brabant, Belgium

Site Status

Cliniques Universitaires Saint-Luc

Brussels, , Belgium

Site Status

Alberta Children's Hospital

Calgary, Alberta, Canada

Site Status

University of Alberta

Edmonton, Alberta, Canada

Site Status

Children's and Women's Health Centre of British Columbia

Vancouver, British Columbia, Canada

Site Status

Children's Hospital of Winnipeg

Winnipeg, Manitoba, Canada

Site Status

IWK Health Centre

Halifax, Nova Scotia, Canada

Site Status

McMaster Children's Hospital

Hamilton, Ontario, Canada

Site Status

London Health Sciences Centre University Hospital

London, Ontario, Canada

Site Status

Toronto Hospital for Sick Children

Toronto, Ontario, Canada

Site Status

Centre Hospitalier Universitaire Sainte-Justine

Montreal, Quebec, Canada

Site Status

McGill University Health Centre Glen Site

Montreal, Quebec, Canada

Site Status

Hopital Jeanne de Flandre

Lille, Hauts-de-France, France

Site Status

Hopital de la Timone

Marseille, Provence-Alpes-Côte d'Azur Region, France

Site Status

Hopital Necker-Enfants Malades

Paris, Île-de-France Region, France

Site Status

Hopital Robert Debre

Paris, Île-de-France Region, France

Site Status

Universitatsklinikum Ulm

Ulm, Baden-Wurttemberg, Germany

Site Status

Ludwig-Maximillians-Universitat Munchen

München, Bavaria, Germany

Site Status

Universitatsmedizin Rostock - Kinder und Jugendklinik

Rostock, Mecklenburg-Vorpommern, Germany

Site Status

Universitatsklinikum Aachen

Aachen, North Rhine-Westphalia, Germany

Site Status

Universitaetsklinikum Leipzig AoeR

Leipzig, Saxony, Germany

Site Status

BAZ Megyei Korhaz es Egyetemi Oktatokorhaz

Miskolc, Borsod-Abauj Zemplen county, Hungary

Site Status

Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont

Szeged, Csongrád megye, Hungary

Site Status

Soproni Erzsebet Oktato Korhaz es Rehabilitacios Intezet

Sopron, Győr-Moson-Sopron, Hungary

Site Status

Debreceni Egyetem Klinikai Kozpont

Debrecen, Hajdú-Bihar, Hungary

Site Status

Semmelweis Egyetem

Budapest, , Hungary

Site Status

Soroka University Medical Center

Beersheba, Beersheba, Israel

Site Status

Schneider Children's Medical Center of Israel

Petach Tikvah, Petah Tiqwa, Israel

Site Status

Assaf Harofeh Medical Center

Ẕerifin, Rehoboth, Israel

Site Status

The Edmond and Lily Safra Children's Hospital - Sheba Medical Center

Ramat Gan, Tel Aviv, Israel

Site Status

Rambam Health Care Campus - Rambam Medical Center

Haifa, , Israel

Site Status

Carmel Medical Center

Haifa, , Israel

Site Status

Shaare Zedek Medical Center

Jerusalem, , Israel

Site Status

Tel Aviv Sourasky Medical Center

Tel Aviv, , Israel

Site Status

Radboud Universitair Medisch Centrum

Nijmegen, GA, Netherlands

Site Status

Emma Kinderziekenhuis AMC

Amsterdam, North Holland, Netherlands

Site Status

Isala Klinieken

Zwolle, Overijssel, Netherlands

Site Status

Erasmus University Medical Center

Rotterdam, South Holland, Netherlands

Site Status

Uniwersytecki Szpital Dzieciecy w Krakowie

Krakow, Lesser Poland Voivodeship, Poland

Site Status

Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu

Wroclaw, Lower Silesian Voivodeship, Poland

Site Status

Warszawski Uniwersytet Medyczny

Warsaw, Masovian Voivodeship, Poland

Site Status

Gabinet Lekarski Dr. Hab. N. Med. Bartosz Korczowski

Rzeszów, Podkarpackie Voivodeship, Poland

Site Status

Uniwersytecki Dzieciecy Szpital Kliniczny im. L. Zamenhofa w Bialymstoku

Bialystok, Podlaskie Voivodeship, Poland

Site Status

Copernicus Podmiot Leczniczy

Gdansk, Pomeranian Voivodeship, Poland

Site Status

Samodzielny Publiczny Specjalistyczny Zaklad Opieki Zdrowotnej ZDROJE

Szczecin, West Pomeranian Voivodeship, Poland

Site Status

Centralny Szpital Kliniczny Uniwersytetu Medycznego w Lodzi Osrodek Pediatryczny im Marii Konopnic

Lodz, Łódź Voivodeship, Poland

Site Status

Instytut Centrum Zdrowia Matki Polki

Lodz, Łódź Voivodeship, Poland

Site Status

National Scientific Center of Radiological Medicine of NAMS of Ukraine

Kyiv, KIEV CITY, Ukraine

Site Status

Kharkiv Regional Clinical Children's Hospital

Kharkiv, , Ukraine

Site Status

Birmingham Women's and Children's NHS Foundation Trust

Birmingham, England, United Kingdom

Site Status

Cambridge University Hospitals NHS Foundation Trust

Cambridge, England, United Kingdom

Site Status

Barts and The London NHS Trust

London, England, United Kingdom

Site Status

King's College Hospital

London, England, United Kingdom

Site Status

Great Ormond Street Hospital for Children NHS Trust

London, England, United Kingdom

Site Status

Central Manchester University Hospitals NHS Foundation Trust

Manchester, England, United Kingdom

Site Status

Nottingham University Hospitals NHS Trust

Nottingham, England, United Kingdom

Site Status

Oxford University Hospitals NHS Foundation Trust

Oxford, England, United Kingdom

Site Status

Sheffield Children's NHS Foundation Trust

Sheffield, England, United Kingdom

Site Status

NHS Greater Glasgow and Clyde

Glasgow, Scotland, United Kingdom

Site Status

Countries

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United States Belgium Canada France Germany Hungary Israel Netherlands Poland Ukraine United Kingdom

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2017-002231-41

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1174-2041

Identifier Type: OTHER

Identifier Source: secondary_id

MLN0002-2003CTIL

Identifier Type: REGISTRY

Identifier Source: secondary_id

17/NE/0257

Identifier Type: REGISTRY

Identifier Source: secondary_id

MOH_2017-09-18_000675

Identifier Type: OTHER

Identifier Source: secondary_id

MLN0002-2003

Identifier Type: -

Identifier Source: org_study_id