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Summary

for people ages 2–17 (full criteria)
at San Francisco, California and other locations
study started
estimated completion:

Description

Summary

The purpose of this study is to evaluate vedolizumab pharmacokinetics (PK), safety and tolerability in pediatric participants with moderately to severely active ulcerative colitis or Crohn's disease.

Official Title

A Phase 2, Randomized, Double-Blind, Dose-Ranging Study to Determine the Pharmacokinetics, Safety and Tolerability of Vedolizumab IV in Pediatric Subjects With Ulcerative Colitis or Crohn's Disease

Details

The drug being tested in this study is called vedolizumab. Vedolizumab is being tested to treat pediatric participants who have moderately to severely active ulcerative colitis (UC) or Crohn's disease (CD). This study will look at the pharmacokinetics (PK), efficacy, immunogenicity, safety, and tolerability in participants who take vedolizumab.

The study will enroll approximately 80 patients. Participants will be randomly assigned (by chance, like flipping a coin) to one of the two dose regimens (high or low) per weight group 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 intravenous (IV) infusion. Participants assigned to the low dose group who do not achieve clinical response (based on pediatric ulcerative colitis/Crohn's disease activity index) at Week 14 will receive the high dose (ie, 300 mg for participants ≥30 kg baseline weight and 200 mg for participants <30 kg baseline weight) of vedolizumab IV 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 an 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.

Keywords

Ulcerative Colitis Crohn's Disease Drug therapy Crohn Disease Colitis Ulcer Colitis, Ulcerative Vedolizumab

Eligibility

You can join if…

Open to people ages 2–17

  1. Has a medical history of moderately to severely active ulcerative colitis (UC) during Screening defined as total of Mayo subscores of stool frequency and rectal bleeding ≥4 and Mayo endoscopy subscore ≥2, or has moderately to severely active Crohn's disease(CD) defined as simple endoscopic score for Crohn's disease (SES-CD) ≥7, and the Crohn's disease activity index (CDAI) components of average daily abdominal pain score of >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.
  2. Has evidence of UC extending proximal to the rectum (i.e., not limited to proctitis)or evidence of CD involving the ileum and/or colon, at a minimum.
  3. 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.
  4. Has a family history of colorectal cancer (ie, first-degree relative), personal history of increased colorectal cancer risk, or other known risk factor must be up-to-date on colorectal cancer surveillance.
  5. The participant's vaccinations are up to date.
  6. 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 mg/kg daily orally for 2 weeks or intravenous (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 mg/kg/day) or 6-mercaptopurine (6-MP)mg/kg (≥1.0 mg/kg/day) or methotrexate (MTX) (≥10 mg/m2 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,i.e., 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).

  1. The participant may be receiving a therapeutic dose of the following drugs:
  2. Oral 5-aminosalicylic acid (5-ASA) compounds, providing the dose has been stable for the 2 weeks prior to first dose of study drug.
  3. 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.
  4. Probiotics (eg, Saccharomyces boulardii), provided the dose has been stable for the 2 weeks prior to first dose of study drug.
  5. Antidiarrheals (eg, loperamide, diphenoxylate with atropine) for control of chronic diarrhea.
  6. Antibiotics used for the treatment of CD (eg, ciprofloxacin, metronidazole),providing the dose has been stable for the 2 weeks prior to first dose of study drug.
  7. Azathioprine or 6-MP, provided the dose has been stable for the 8 weeks prior to first dose of study drug.
  8. Methotrexate (MTX), provided the dose has been stable for the 8 weeks prior to first dose of study drug.

You CAN'T join if...

  1. Has had previous exposure to approved or investigational anti-integrins (eg,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 any of the following:
  8. 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. OR
  • Chest X-ray within 3 months of Screening that is suspicious for pulmonary TB, and a positive or 2 successive indeterminate QuantiFERON tests within 30 days prior to Screening or during the Screening Period.
  • Clinically significant current or recent history (within 1 year prior to enrollment)of alcohol dependence or illicit drug use.
  • Has a current diagnosis of indeterminate colitis (Inflammatory bowel disease unclassified [IBDU]).
  • . Has evidence of abdominal abscess or toxic megacolon at the initial Screening Visit.
  • . Has ileostomy, colostomy, ileo-anal pouch, or known fixed symptomatic stenosis of the intestine.
  • . Has extensive colonic resection, eg, subtotal or total colectomy.
  • . has a history or evidence of adenomatous colonic polyps that have not been removed.
  • . Has a history or evidence of colonic mucosal dysplasia.
  • . Has chronic hepatitis B virus (HBV) infection* or chronic hepatitis C virus (HCV)infection. * HBV immune participants (ie, being hepatitis B surface antigen [HBsAg]negative and hepatitis B antibody positive) may be included, however.
  • . Has any identified congenital or acquired immunodeficiency (eg, common variable immunodeficiency, human immunodeficiency virus [HIV] infection, organ transplantation).
  • . 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.
  • . 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 (eg, >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.
  • . Has a history of any major neurological disorders, including stroke, multiple sclerosis, brain tumor, or neurodegenerative disease.
  • . Has history of lupus or lupus-related conditions.
  • . 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.

Locations

  • University of California San Francisco not yet accepting patients
    San Francisco, California, 94143-0135, United States
  • Cedars-Sinai Medical Center not yet accepting patients
    Los Angeles, California, 90048, United States
  • Children's Hospital of Orange County not yet accepting patients
    Orange, California, 92868, United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Takeda
ID
NCT03138655
Phase
Phase 2
Study Type
Interventional
Last Updated
November 23, 2017
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