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A Pharmacokinetic Study of Ustekinumab in Pediatric Subjects With Moderately to Severely Active Crohn's Disease

Phase 1
Completed
Conditions
Crohn Disease
Interventions
Registration Number
NCT02968108
Lead Sponsor
Janssen Research & Development, LLC
Brief Summary

The purpose of this study is to evaluate the pharmacokinetics (PK) of ustekinumab in subjects from 2 through less than (\<) 18 years old in the USA, or 6 through less than (\<) 18 years old in other countries and determine if it is similar to that observed in adults with moderately to severely active Crohn's disease (CD). Also to assess the safety, immunogenicity and efficacy of ustekinumab in the treatment of moderately to severely active CD. The main part of the study continues to Week 16, at which point all subjects who are receiving benefit from ustekinumab maintenance therapy (as determined by the investigator) are eligible to enter the long-term extension (LTE) and continue to receive ustekinumab. The study extension ends at Week 268 or upon availability of the LTE basket study (CNTO1275ISD3001) whichever occurs first. If participants do not consent/assent to the LTE basket study, they will continue safety follow-up for approximately 20 weeks after the last study agent administration.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
45
Inclusion Criteria
  • Be a pediatric subject 2 to less than (<) 18 years old in the US, 6 to <18 years old elsewhere, of either gender with a body weight of greater than or equal to (>=) 10 kilogram (kg)
  • Have Crohn's disease (CD) or fistulizing CD of at least 3 months duration, with active colitis, ileitis, or ileocolitis, confirmed at any time in the past by radiography, histology, and/or endoscopy
  • Must have moderately to severely active CD defined by: Baseline pediatric Crohn's disease activity index (PCDAI) score of greater than (>)30 and at least one of the following: An abnormal C-reactive protein (CRP) >0.3 milligram per deciliter (mg/dL) or 3.0 milligram per liter (mg/L) at screening) or fecal calprotectin >250 milligram per kilogram (mg/kg) at screening or ileocolonoscopy with evidence of active CD (defined as ulcerations in the ileum and/or colon) during screening into this study including at the baseline visit
  • Prior or current medication for CD must include at least 1 of the following: Current treatment with at least 1 of the following therapies: oral corticosteroids, the immunomodulators azathioprine, 6-MP, or methotrexate, or currently have or have had a history of corticosteroid dependency, or have a history of failure to respond to, or tolerate, at least 1 of the following therapies including oral or IV corticosteroids or the immunomodulators 6-mercaptopurine, azathioprine, or methotrexate,or have required more than 3 courses of oral or IV corticosteroids in the past year
  • Have negative stool results for enteric pathogens. Stool studies must include a stool culture and Clostridium difficile toxin assay. These must have been performed during screening or the current episode of disease exacerbation as long as the stool studies were performed within 4 months prior to the first administration of study agent
Exclusion Criteria
  • Has complications of CD such as symptomatic strictures or stenosis, short gut syndrome, or any other manifestation that might be anticipated to require surgery, could preclude the use of the PCDAI to assess response to therapy, or would possibly confound the ability to assess the effect of treatment with ustekinumab
  • Currently has or is suspected to have an abscess. Recent cutaneous and perianal abscesses are not exclusionary if drained and adequately treated at least 3 weeks prior to baseline, or 8 weeks prior to baseline for intra-abdominal abscesses, provided that there is no anticipated need for any further surgery. Participant with active fistulas may be included if there is no anticipation of a need for surgery and there are currently no abscesses identified
  • Has had any kind of bowel resection within 6 months or any other intra-abdominal surgery within 3 months prior to baseline
  • Has a draining (that is (i.e.), functioning) stoma or ostomy
  • Presence or history of any malignancy including presence or history of lymphoproliferative disease including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy of unusual size or location (example, nodes in the posterior triangle of the neck, infraclavicular, epitrochlear, or periaortic areas), or clinically significant hepatomegaly or splenomegaly

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Group1: Ustekinumab Dose Regimen 1UstekinumabSubjects will receive a single intravenous (IV) induction dose of 3 milligram per kilogram (mg/kg) for subjects less than \< 40 kilogram (kg) or 130 milligram (mg) for subjects greater than or equal to \>= 40 kg at Week 0 followed by subcutaneous (SC) maintenance dose of 2 mg/kg for subjects \< 40 kg or 90 mg for subjects \>= 40 kg at week 8.
Group2: Ustekinumab Dose Regimen 2UstekinumabSubjects will receive a single Intravenous (IV) dose of 9 mg/kg for subjects \<40 kg or 390 mg for subjects \>= 40 kg at Week 0 followed by SC maintenance dose of 2 mg/kg for subjects \<40 kg or 90 mg for subjects \>= 40 kg at week 8.
Primary Outcome Measures
NameTimeMethod
Serum Ustekinumab Concentrations Over TimeUp to Week 16

Serum samples will be collected to measure seum concentrations of Ustekinumab.

Secondary Outcome Measures
NameTimeMethod
Clinical Response as Measured by the Pediatric Crohn's Disease Activity Index (PCDAI) ScoreWeek 6

Clinical Response is defined as greater than or equal to (\>=) 15-point reduction from baseline in the total Pediatric Crohn's Disease Activity Index (PCDAI) score, accompanied by a total PDCAI score of less than or equal to (\<=) 30 points. PCDAI is an index used to measure disease activity of pediatric patients with Crohn's Disease assessing abdominal pain, stool frequency, patient functioning, hematocrit, erythrocyte sedimentation rate, albumin, weight, height, abdominal tenderness or mass, perirectal disease, and extraintestinal manifestations. It ranges from 0 to 100; higher scores indicate more active disease.

Clinical Remission as Measured by the Pediatric Crohn's Disease Activity Index (PCDAI) ScoreWeek 8

Clinical remission is defined as PCDAI score of less than or equal to (\<=) 10. PCDAI is an index used to measure disease activity of pediatric patients with Crohn's Disease assessing abdominal pain, stool frequency, patient functioning, hematocrit, erythrocyte, sedimentation rate, albumin, weight, height, abdominal tenderness or mass, perirectal disease, and extraintestinal manifestations. It ranges from 0 to 100; higher scores indicate more active disease.

Trial Locations

Locations (26)

Centre Hospitalier Sainte Justine

🇨🇦

Montreal, Quebec, Canada

Uniwersytecki Szpital Kliniczny im Jana Mikulicza Radeckiego we Wroclawiu

🇵🇱

Wroclaw, Poland

Universitair Kinderziekenhuis Koningin Fabiola

🇧🇪

Brussel, Belgium

UZ Brussel

🇧🇪

Jette, Belgium

Stollery Children's Hospital

🇨🇦

Edmonton, Alberta, Canada

Emory University

🇺🇸

Atlanta, Georgia, United States

Methodist Medical Center of Illinois

🇺🇸

Peoria, Illinois, United States

Center For Digestive Health Systems-Greenville

🇺🇸

Greenville, South Carolina, United States

UZ Gent

🇧🇪

Gent, Belgium

Hôpital Necker

🇫🇷

Paris, France

Dr. von Haunersches Kinderspital

🇩🇪

Munich, Germany

WIP Warsaw IBD Point Profesor Kierkus

🇵🇱

Warszawa, Poland

Children's Hospital of Western Ontario

🇨🇦

London, Ontario, Canada

Cedars Sinai Medical Center

🇺🇸

Los Angeles, California, United States

Cliniques Universitaires Saint Luc

🇧🇪

Bruxelles, Belgium

HELIOS Klinikum Wuppertal GmbH

🇩🇪

Wuppertal, Germany

Connecticut Childrens Medical Center

🇺🇸

Hartford, Connecticut, United States

Mayo Clinic

🇺🇸

Rochester, Minnesota, United States

Mount Sinai

🇺🇸

New York, New York, United States

Childrens Hospital Of Philadelphia

🇺🇸

Philadelphia, Pennsylvania, United States

UZ Leuven

🇧🇪

Leuven, Belgium

Children's Center For Digestive Healthcare, Llc

🇺🇸

Atlanta, Georgia, United States

British Columbia Children's Hospital

🇨🇦

Vancouver, British Columbia, Canada

Hospital For Sick Children

🇨🇦

Toronto, Ontario, Canada

Hôpital Robert Debré

🇫🇷

Paris, France

Instytut Centrum Zdrowia Matki Polki

🇵🇱

Lodz, Poland

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