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

Crohn Disease Clinical Trial

— STELARA  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02968108
• Other study ID #: CR108233
• Secondary ID: CNTO1275CRD10012
• Status: Completed
• Phase: Phase 1
• Start date: January 18, 2017
• Est. completion date: March 18, 2022

Study information

• Verified date: May 2023
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: March 18, 2022
• Est. primary completion date: September 19, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Crohn Disease

Intervention

Drug:
• Ustekinumab
Subjects will receive a single IV administration of ustekinumab (3 mg/kg for subjects <40 kg or 130 mg for subjects >= 40 kg in Group 1 and 9 mg/kg for subjects < 40 kg or 390 mg for subjects >= 40 kg in group 2) at week 0 followed by SC administration of ustekinumab (2 mg/kg for subjects < 40 kg or 90 mg for subjects >= 40 kg at Week 8.

Locations

Country	Name	City	State
Belgium	Cliniques Universitaires Saint-Luc	Brussel
Belgium	Universitair Kinderziekenhuis Koningin Fabiola	Brussel
Belgium	UZ Gent	Gent
Belgium	UZ Brussel	Jette
Belgium	UZ Leuven	Leuven
Canada	Stollery Children's Hospital	Edmonton	Alberta
Canada	Children's Hospital of Western Ontario	London	Ontario
Canada	Centre Hospitalier Sainte Justine	Montreal	Quebec
Canada	Hospital For Sick Children	Toronto	Ontario
Canada	British Columbia Children's Hospital	Vancouver
France	Hôpital Necker	Paris
France	Hôpital Robert Debré	Paris
Germany	Dr. von Haunersches Kinderspital	Munich
Germany	HELIOS Klinikum Wuppertal GmbH	Wuppertal
Poland	Instytut Centrum Zdrowia Matki Polki	Lodz
Poland	WIP Warsaw IBD Point Profesor Kierkus	Warszawa
Poland	Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu	Wroclaw
United States	Children's Center For Digestive Healthcare, Llc	Atlanta	Georgia
United States	Emory University	Atlanta	Georgia
United States	Center For Digestive Health Systems-Greenville	Greenville	South Carolina
United States	Connecticut Childrens Medical Center	Hartford	Connecticut
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	Mount Sinai	New York	New York
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	Childrens Hospital Of Philadelphia	Philadelphia	Pennsylvania
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  France,  Germany,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Serum Ustekinumab Concentrations Over Time	Serum samples will be collected to measure seum concentrations of Ustekinumab.	Up to Week 16
Secondary	Clinical Response as Measured by the Pediatric Crohn's Disease Activity Index (PCDAI) Score	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.	Week 6
Secondary	Clinical Remission as Measured by the Pediatric Crohn's Disease Activity Index (PCDAI) Score	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.	Week 8