Vedolizumab IV in Pediatric Participants With Ulcerative Colitis (UC) or Crohn's Disease (CD)
- Registration Number
- NCT03138655
- Lead Sponsor
- Takeda
- Brief Summary
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
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 89
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Participants weighs >=10 kg at the time of randomization.
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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.
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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.
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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.
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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.
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The participant's vaccinations are up to date.
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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).
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The participant may be receiving a therapeutic dose of the following drugs:
- Oral 5-aminosalicylic acid (5-ASA) compounds, providing the dose has been stable for the 2 weeks prior to first dose of study drug.
- 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.
- Probiotics (example, Saccharomyces boulardii), provided the dose has been stable for the 2 weeks prior to first dose of study drug.
- Antidiarrheals (example, loperamide, diphenoxylate with atropine) for control of chronic diarrhea.
- 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.
- Azathioprine or 6-MP, provided the dose has been stable for the 8 weeks prior to first dose of study drug.
- Methotrexate (MTX), provided the dose has been stable for the 8 weeks prior to first dose of study drug.
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Has had previous exposure to approved or investigational anti-integrins (example, natalizumab, efalizumab, etrolizumab, or AMG 181) or MAdCAM-1 antagonists, or rituximab.
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Has had prior exposure to vedolizumab.
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Has a positive progressive multifocal leukoencephalopathy (PML) subjective symptom checklist prior to the administration of the first dose of study drug.
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Requires surgical intervention for UC or CD, or is anticipated to require surgical intervention for UC or CD during this study.
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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.
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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.
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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.
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Clinically significant current or recent history (within 1 year prior to enrollment) of alcohol dependence or illicit drug use.
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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.
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Has evidence of abdominal abscess or toxic megacolon at the initial Screening Visit.
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Has ileostomy, colostomy, ileo-anal pouch, or known fixed symptomatic stenosis of the intestine.
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Has extensive colonic resection, example, subtotal or total colectomy.
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Has a history or evidence of adenomatous colonic polyps that have not been removed.
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Has a history or evidence of colonic mucosal dysplasia.
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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.
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Has any identified congenital or acquired immunodeficiency (example, common variable immunodeficiency, human immunodeficiency virus [HIV] infection, organ transplantation).
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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.
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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.
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Has a history of any major neurological disorders, including stroke, multiple sclerosis, brain tumor, or neurodegenerative disease.
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Has history of lupus.
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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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description CD: <30 kg Participants, Vedolizumab 200 mg Vedolizumab 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. UC: >=30 kg Participants, Vedolizumab 150 mg Vedolizumab 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. UC: <30 kg Participants, Vedolizumab 100 mg Vedolizumab 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. CD: <30 kg Participants, Vedolizumab 100 mg Vedolizumab 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. UC: <30 kg Participants, Vedolizumab 200 mg Vedolizumab 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. UC: >=30 kg Participants, Vedolizumab 300 mg Vedolizumab 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. CD: >=30 kg Participants, Vedolizumab 150 mg Vedolizumab 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. CD: >=30 kg Participants, Vedolizumab 300 mg Vedolizumab 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.
- Primary Outcome Measures
Name Time Method Cav,Week 14: Average Serum Concentration During a Dosing Interval at Week 14 From Day 43 (week 6) post-dose up to pre-dose Day 99 (Week 14) AUCWeek 14: Area Under the Serum Concentration-time Curve at Week 14 From Day 43 (Week 6) post-dose up to pre-dose Day 99 (Week 14) Ctrough,Week 14: Observed Serum Concentration at the End of a Dosing Interval at Week 14 At the end of a dosing interval at Week 14
- Secondary Outcome Measures
Name Time Method Percentage of UC Participants Who Achieve Clinical Response Based on Complete Mayo Score Baseline (Day 1) and Week 14 Clinical response was defined as a reduction in complete Mayo score of \>= 3 points and \>=30 % from Baseline with an accompanying decrease in rectal bleeding sub-score of \>=1 point(s) or absolute rectal bleeding sub-score of \<= 1 point. Mayo score was used in to assess UC disease activity. It consisted of 4 subscales: stool frequency, rectal bleeding, findings on endoscopy and physician's global assessment. Each subscale was scored on a scale of 0 to 3, where 0= normal condition and 3 = severe disease condition. The total Mayo score ranged from 0 to 12, with higher scores indicating more severe disease.
Percentage of CD Participants Who Achieve Clinical Response Based on Crohn's Disease Activity Index (CDAI) Baseline (Day 1) and Week 14 Clinical response was defined as \>=70 points decrease from Baseline in CDAI score at Week 14. The CDAI evaluated severity of signs and symptoms of CD. Information was collected on number of liquid stools, intensity of abdominal pain, general well-being, presence of comorbid conditions, use of medications for diarrhea, physical examination, and laboratory, yielding 8 items that were combined with data from a 7-day diary to obtain total CDAI score. Index values of 150 and below were associated with quiescent disease; values above that indicated active disease, values \>=220 indicated moderate to severe disease, and values above 450 were seen with extremely severe disease.
Trial Locations
- Locations (88)
Children's Center for Digestive Healthcare
🇺🇸Atlanta, Georgia, United States
Ann & Robert H. Lurie Children's Hospital of Chicago
🇺🇸Chicago, Illinois, United States
University Hospitals Rainbow Babies & Children's Hospital
🇺🇸Cleveland, Ohio, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Nicklaus Children's Hospital
🇺🇸Miami, Florida, United States
Indiana University School of Medicine - Indianapolis
🇺🇸Indianapolis, Indiana, United States
Seattle Children's Hospital
🇺🇸Seattle, Washington, United States
Texas Children's Hospital
🇺🇸Houston, Texas, United States
Children's Hospital of Orange County
🇺🇸Orange, California, United States
Central Manchester University Hospitals NHS Foundation Trust
🇬🇧Manchester, England, United Kingdom
Great Ormond Street Hospital for Children NHS Trust
🇬🇧London, England, United Kingdom
Universitatsmedizin Rostock - Kinder und Jugendklinik
🇩🇪Rostock, Mecklenburg-vorpommern, Germany
Birmingham Women's and Children's NHS Foundation Trust
🇬🇧Birmingham, England, United Kingdom
Oxford University Hospitals NHS Foundation Trust
🇬🇧Oxford, England, United Kingdom
Sheffield Children's NHS Foundation Trust
🇬🇧Sheffield, England, United Kingdom
Nemours Children's Clinic
🇺🇸Wilmington, Delaware, United States
The Edmond and Lily Safra Children's Hospital - Sheba Medical Center
🇮🇱Ramat Gan, Tel Aviv, Israel
Shaare Zedek Medical Center
🇮🇱Jerusalem, Israel
Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont
🇭🇺Szeged, Csongrad, Hungary
Mount Sinai Medical Center
🇺🇸New York, New York, United States
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
Connecticut Children's Medical Center
🇺🇸Hartford, Connecticut, United States
Nemours Childrens Specialty Care - Jacksonville
🇺🇸Jacksonville, Florida, United States
Mayo Clinic - Rochester
🇺🇸Rochester, Minnesota, United States
Children's and Women's Health Centre of British Columbia
🇨🇦Vancouver, British Columbia, Canada
Cliniques Universitaires Saint-Luc
🇧🇪Brussels, Belgium
Alberta Children's Hospital
🇨🇦Calgary, Alberta, Canada
Children's Hospital of Winnipeg
🇨🇦Winnipeg, Manitoba, Canada
IWK Health Centre
🇨🇦Halifax, Nova Scotia, Canada
London Health Sciences Centre University Hospital
🇨🇦London, Ontario, Canada
McMaster Children's Hospital
🇨🇦Hamilton, Ontario, Canada
Hopital Jeanne de Flandre
🇫🇷Lille, NORD Pas-de-calais, France
Hopital Necker-Enfants Malades
🇫🇷Paris Cedex 15, Ile-de-france, France
Hopital Robert Debre
🇫🇷Paris Cedex 19, Ile-de-france, France
Universitatsklinikum Ulm
🇩🇪Ulm, Baden-wuerttemberg, Germany
Universitaetsklinikum Leipzig AoeR
🇩🇪Leipzig, Sachsen, Germany
Ludwig-Maximillians-Universitat Munchen
🇩🇪Munchen, Bayern, Germany
Schneider Children's Medical Center of Israel
🇮🇱Petach Tikvah, Petah Tiqwa, Israel
Debreceni Egyetem Klinikai Kozpont
🇭🇺Debrecen, Hajdu-bihar, Hungary
Rambam Health Care Campus - Rambam Medical Center
🇮🇱Haifa, Israel
Carmel Medical Center
🇮🇱Haifa, Israel
Instytut Centrum Zdrowia Matki Polki
🇵🇱Lodz, Lodzkie, Poland
Uniwersytecki Dzieciecy Szpital Kliniczny im. L. Zamenhofa w Bialymstoku
🇵🇱Bialystok, Podlaskie, Poland
Copernicus Podmiot Leczniczy
🇵🇱Gdansk, Pomorskie, Poland
Samodzielny Publiczny Specjalistyczny Zaklad Opieki Zdrowotnej ZDROJE
🇵🇱Szczecin, Zachodniopomorskie, Poland
Kharkiv Regional Clinical Children's Hospital
🇺🇦Kharkiv, Ukraine
Cambridge University Hospitals NHS Foundation Trust
🇬🇧Cambridge, England, United Kingdom
King's College Hospital
🇬🇧London, England, United Kingdom
NHS Greater Glasgow and Clyde
🇬🇧Glasgow, Scotland, United Kingdom
Nottingham University Hospitals NHS Trust
🇬🇧Nottingham, England, United Kingdom
University of Alberta
🇨🇦Edmonton, Alberta, Canada
University of California San Francisco
🇺🇸San Francisco, California, United States
Children's Specialty Group - Medical Center Location
🇺🇸Norfolk, Virginia, United States
Boston Children's Hospital
🇺🇸Boston, Massachusetts, United States
Washington University in St. Louis
🇺🇸Saint Louis, Missouri, United States
The Children's Hospital at Montefiore
🇺🇸Bronx, New York, United States
Northwell Health
🇺🇸Lake Success, New York, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
The Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Children's Hospital of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States
Childrens Medical Center of Dallas
🇺🇸Dallas, Texas, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
Universitair Ziekenhuis Brussel
🇧🇪Brussel, Brussels, Belgium
Hopital Universitaire des Enfants Reine Fabiola
🇧🇪Bruxelles, Brussels, Belgium
Universitair Ziekenhuis Leuven
🇧🇪Leuven, Flemish Brabant, Belgium
Toronto Hospital for Sick Children
🇨🇦Toronto, Ontario, Canada
Centre Hospitalier Universitaire Sainte-Justine
🇨🇦Montreal, Quebec, Canada
McGill University Health Centre Glen Site
🇨🇦Montreal, Quebec, Canada
Hopital de la Timone
🇫🇷Marseille Cedex 5, Provence Alpes COTE D'azur, France
Universitatsklinikum Aachen
🇩🇪Aachen, Nordrhein-westfalen, Germany
BAZ Megyei Korhaz es Egyetemi Oktatokorhaz
🇭🇺Miskolc, Borsod-abauj-zemplen, Hungary
Soproni Erzsebet Oktato Korhaz es Rehabilitacios Intezet
🇭🇺Sopron, Gyor-moson-sopron, Hungary
Semmelweis Egyetem
🇭🇺Budapest, Hungary
Soroka University Medical Center
🇮🇱Beer-sheva, Beersheba, Israel
Assaf Harofeh Medical Center
🇮🇱Zerifin, Rehoboth, Israel
Emma Kinderziekenhuis AMC
🇳🇱Amsterdam, Noord-holland, Netherlands
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
Radboud Universitair Medisch Centrum
🇳🇱Nijmegen, GA, Netherlands
Erasmus University Medical Center
🇳🇱Rotterdam, Zuid-holland, Netherlands
Isala Klinieken
🇳🇱Zwolle, Overijssel, Netherlands
Centralny Szpital Kliniczny Uniwersytetu Medycznego w Lodzi Osrodek Pediatryczny im Marii Konopnic
🇵🇱Lodz, Lodzkie, Poland
Warszawski Uniwersytet Medyczny
🇵🇱Warsaw, Mazowieckie, Poland
Barts and The London NHS Trust
🇬🇧London, England, United Kingdom
Uniwersytecki Szpital Dzieciecy w Krakowie
🇵🇱Krakow, Malopolskie, Poland
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu
🇵🇱Wroclaw, Dolnoslaskie, Poland
Gabinet Lekarski Dr. Hab. N. Med. Bartosz Korczowski
🇵🇱Rzeszow, Podkarpackie, Poland
National Scientific Center of Radiological Medicine of NAMS of Ukraine
🇺🇦Kyiv, Kiev City, Ukraine