Clinical trial NCT04673357: A Study of Ustekinumab in Pediatric Participants With Moderately to Severely Active Crohn's Disease
Official title: A Phase 3 Study of the Efficacy, Safety, and Pharmacokinetics of Ustekinumab as Open-label Intravenous Induction Treatment Followed by Randomized Double-blind Subcutaneous Ustekinumab Maintenance in Pediatric Participants With Moderately to Severely Active Crohn's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Crohn Disease
Keywords: Pediatric
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2020-12-17
Enrollment: 101
Sex: ALL
Minimum age (years): 2
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy of ustekinumab dosing in inducing clinical remission (Global) and in maintaining clinical remission (US); to evaluate the safety profile and ustekinumab exposure (pharmacokinetics \[PK\]) in pediatric participants with moderately to severely active Crohn's disease.


Eligibility criteria: Inclusion Criteria:

* Have Crohn's disease or fistulizing Crohn's disease with active colitis, ileitis, or ileocolitis, confirmed at any time in the past by endoscopy and histology
* Must have moderately to severely active Crohn's disease (as defined by a baseline Pediatric Crohn's Disease Activity Index \[PCDAI\] score greater than \[\>\] 30); have ileocolonoscopy with evidence of active Crohn's disease defined as presence of ulceration (which is equal to Simple Endoscopic Score for Crohn's disease \[SES-CD\] score greater than or equals to \[\>=\] 3) during screening into this study. The ileocolonoscopy procedure must occur within approximately 3 weeks prior to the administration of study intervention at Week 0 (Induction Period). A video ileocolonoscopy recorded within 3 months prior to the Week 0 (Induction Period) visit may be used in case of rescreening of a participant who had an ileocolonoscopy but failed the initial screening for another reason, on a case-by-case basis, after consultation with the sponsor. If unable to evaluate ulceration due to stricture or inadequate bowel preparation, at least one of the following criteria may instead be applied: 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 of \>= 250 milligram per kilogram \[mg/kg\] or \>= 250 microgram per gram \[mcg/g\] at screening
* If receiving enteral nutrition, must have been on a stable regimen for at least 2 weeks prior to induction week 0 (Week I-0)
* Females of childbearing potential must have a negative highly sensitive urine pregnancy test at screening and at Week I-0 prior to study intervention administration

Exclusion Criteria:

* Has complications of Crohn's disease such as symptomatic strictures or stenosis, short gut syndrome, or any other manifestation that might be anticipated to require surgery, that 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
* Have a history of latent or active granulomatous infection, histoplasmosis, or coccidioidomycosis, or have had a nontuberculous mycobacterial infection prior to screening
* 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), and monoclonal gammopathy of undetermined significance, or clinically significant hepatomegaly or splenomegaly
* Have a history of moderate or severe progressive or uncontrolled liver or renal insufficiency; or significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, psychiatric (including suicidality), or metabolic disturbances
* Received an investigational intervention including any investigational vaccines or used an invasive investigational medical device within 3 months before the planned first dose of study intervention or is currently enrolled in an investigational study; receipt of an investigational vaccine for Coronavirus Disease 2019 (COVID-19) is not an automatic exclusion criterion

Primary outcomes:
measure: Number of Participants with Clinical Remission at Induction Week 8
timeFrame: Week 8
measure: Number of Participants with Adverse Events (AEs)
timeFrame: Up to Week 74
measure: Number of Participants with Serious Adverse Events (SAEs)
timeFrame: Up to Week 74
measure: Number of Participants with AEs leading to Discontinuation of Study Intervention
timeFrame: Up to Week 74
measure: Number of Participants with AEs of Interest
timeFrame: Up to Week 74
measure: Number of Participants with Abnormalities in Clinical Laboratory Parameters
timeFrame: Up to Week 52
measure: Number of Participants with Reactions Temporally Associated with Intravenous (IV) Infusion (Induction Period)
timeFrame: Up to Week 8 (Induction period)
measure: Number of Participants with Subcutaneous (SC) Injection-Site Reactions (Maintenance Period)
timeFrame: Up to Week 44 (Maintenance period)
measure: Serum Ustekinumab Concentrations
timeFrame: Up to Week 52
measure: Number of Participants with Clinical Remission at Maintenance Week 44
timeFrame: Week 44 (Maintenance Period)
Secondary outcomes:
measure: Number of Participants with Clinical Remission as Assessed by short Pediatric Crohn's Disease Activity Index (sPCDAI)
timeFrame: Week 6 (Induction period)
measure: Number of Participants with Clinical Response
timeFrame: Week 8 (Induction period)
measure: Number of Participants with Clinical Response as Assessed by sPCDAI
timeFrame: Week 6 (Induction period)
measure: Number of Participants with Endoscopic Response as Assessed by Simplified Endoscopic Score-Crohn's Disease (SES-CD)
timeFrame: Week 8 (Maintenance period)
measure: Number of Participants with Clinical Response
timeFrame: Week 8 (Maintenance period)
measure: Number of Participants with Clinical Remission
timeFrame: Week 44 (Maintenance period)
measure: Number of Participants with Endoscopic Response as Assessed by SES-CD
timeFrame: Week 44 (Maintenance period)
measure: Number of Participants with Clinical Response
timeFrame: Week 44 (Maintenance period)
measure: Number of Participants with Corticosteroid-free Clinical Remission
timeFrame: Week 44 (Maintenance period)
measure: Number of Participants with Clinical Remission at Week 44 (Maintenance Period) who are in Clinical Remission at Week 8 (Induction Period)
timeFrame: Week 44 (Maintenance Period)
Other outcomes:
Locations:
city: Wilmington
country: United States
facility: Nemours DuPont Hospital for Children
state: Delaware
city: Atlanta
country: United States
facility: Children's Center for Digestive Health Care
state: Georgia
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Morristown
country: United States
facility: Morristown Memorial Hospital
state: New Jersey
city: Charlotte
country: United States
facility: Levine Childrens at Atrium Health
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Hershey
country: United States
facility: Penn State Hershey Children's Hospital
state: Pennsylvania
city: Fort Worth
country: United States
facility: Cook Childrens Medical Center
state: Texas
city: Fairfax
country: United States
facility: Pediatric Specialists Of Virginia
state: Virginia
city: Brussel
country: Belgium
facility: Universitair Kinderziekenhuis Koningin Fabiola
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint Luc
city: Gent
country: Belgium
facility: UZ Gent
city: Jette
country: Belgium
facility: UZ Brussel
city: Leuven
country: Belgium
facility: UZ Leuven
city: Aachen
country: Germany
facility: Universitätsklinikum Aachen
city: Berlin
country: Germany
facility: Charite-Universitätsmedizin Berlin - Berlin
city: Essen
country: Germany
facility: Universitatsklinikum Essen
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Munich
country: Germany
facility: Dr. von Haunersches Kinderspital
city: Regensburg
country: Germany
facility: KUNO Klinik St. Hedwig
city: Ulm
country: Germany
facility: Universitatsklinikum Ulm
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont
city: Miskolc
country: Hungary
facility: Borsod Abauj Zemplen Varmegyei Kozponti Korhaz es Egyetemi Oktato Korhaz
city: Nyiregyhaza
country: Hungary
facility: Szabolcs Szatmar Bereg Varmegyei Oktatokorhaz
city: Szeged
country: Hungary
facility: Szegedi Tudományegyetem, Gyermekgyógyászati Klinika és Gyermekegészségügyi Centrum
city: Be'er Ya'akov
country: Israel
facility: Yitzhak Shamir Medical Center
city: Haifa
country: Israel
facility: Carmel Medical Center
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
city: Petah Tikva
country: Israel
facility: Schneider Children's Medical Center
city: Bunkyo Ku
country: Japan
facility: Juntendo University Hospital
city: Gunma
country: Japan
facility: Gunma University Hospital
city: Ikoma
country: Japan
facility: Kindai University Nara Hospital
city: Kurume
country: Japan
facility: Kurume University Hospital
city: Saitama shi
country: Japan
facility: Saitama Childrens Medical Center
city: Sendai
country: Japan
facility: Miyagi Children's Hospital
city: Setagaya Ku
country: Japan
facility: National Center for Child Health and Development
city: Shimotsuke
country: Japan
facility: Jichi Medical University Hospital
city: Tsu
country: Japan
facility: Mie University Hospital
city: Gdansk
country: Poland
facility: Szpital im. M. Kopernika
city: Krakow
country: Poland
facility: Uniwersytecki Szpital Dzieciecy w Krakowie
city: Rzeszow
country: Poland
facility: Korczowski Bartosz Gabinet Lekarski
city: Warszawa
country: Poland
facility: WIP Warsaw IBD Point Profesor Kierkus
city: Warszawa
country: Poland
facility: Instytut Pomnik Centrum Zdrowia Dziecka
city: Kazan
country: Russian Federation
facility: Kazan State Medical University
city: Moscow
country: Russian Federation
facility: Russian National Research Medical University named after N.I.Pirogov
city: Nizhny Novgorod
country: Russian Federation
facility: Privolzhsky Research Medical University of Ministry of Health of Russian Federation
city: Yaroslavl
country: Russian Federation
facility: Yaroslavl Regional Children's Clinical Hospital
city: Birmingham
country: United Kingdom
facility: Birmingham Children's Hospital
city: Bristol
country: United Kingdom
facility: University Hospitals Bristol and Weston NHS Foundation Trust
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals NHS Foundation Trust
city: Edinburgh
country: United Kingdom
facility: Royal Hospital for Children and Young People
city: London
country: United Kingdom
facility: Royal London Hospital
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: