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

NCT04673357 | Completed Phase 3 Results DMC FDA Drug

• 4 other identifiers: CR108864CNTO1275CRD30042019-004225-242023-504978-38-00
• Study Type: interventional
• Target: 101
• Locations: 9 countries
• Sites: 53

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.

Conditions

Crohn Disease

Keywords

Pediatric

Outcome Measures

Primary Outcomes (10)

• Global Outcome Measure: Percentage of Participants With Clinical Remission at Induction Week 8 (Week I-8)

  Clinical remission was defined as a Pediatric Crohn's Disease Activity Index (PCDAI) score \<=10. The 11-item PCDAI covered five general disease activity domains: symptom history scores (3 items: abdominal pain, stool frequency, and general well-being); laboratory scores (3 items: hematocrit \[HCT\], erythrocyte sedimentation rate \[ESR\], Albumin); growth scores (2 items: weight and height); physical examination scores (2 items: abdomen and perirectal disease); and extraintestinal manifestations. The category of severity for each index item is assigned a score: 0=normal;5=mild abnormality; 10= severe abnormality. For hematocrit and erythrocyte SR, the maximum score =5. For albumin level, the maximum score = 10. All items were summed to derive the total score. The total PCDAI score ranged from 0 to 100, with higher scores indicating greater disease activity.

  Induction Week 8 (Week I-8)

• US-specific Outcome Measure: Percentage of Participants With Clinical Remission at Maintenance Week 44

  Clinical remission was defined as a Pediatric Crohn's Disease Activity Index (PCDAI) score \<=10. The 11-item PCDAI covered five general disease activity domains: symptom history scores (3 items: abdominal pain, stool frequency, and general well-being); laboratory scores (3 items: HCT, ESR, Albumin); growth scores (2 items: weight and height); physical examination scores (2 items: abdomen and perirectal disease); and extraintestinal manifestations. The category of severity for each index item was assigned a score: 0=normal;5=mild abnormality; 10= severe abnormality. For hematocrit and erythrocyte SR, the maximum score= 5. For albumin level, the maximum score= 10. All items were summed to derive the total score. The total PCDAI score ranged from 0 to 100, with higher scores indicating greater disease activity.

  Maintenance Week 44 (Study Week 52)

• Global and US-specific Outcome Measures: Number of Participants With Treatment-emergent Adverse Events (TEAEs)

  Number of participants with TEAEs were reported. An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE did not necessarily have a causal relationship with the intervention. TEAEs were defined as AEs occurring at or after the initial administration of the study intervention.

  Induction Period: From induction Week 0 up to induction Week 8; Maintenance Period: From Maintenance Week 0 (Study Week 8) up to Maintenance Week 44 (Study Week 52)

• Global and US-specific Outcome Measures: Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs)

  Number of participants with TESAEs was reported. An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE did not necessarily have a causal relationship with the intervention. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; or congenital anomaly. TESAEs were defined as any SAE occurring at or after the initial administration of the study intervention.

  Induction Period: From induction Week 0 up to induction Week 8; Maintenance Period: From Maintenance Week 0 (Study Week 8) up to Maintenance Week 44 (Study Week 52)

• Global and US-specific Outcome Measures: Number of Participants With AEs Leading to Discontinuation of Study Intervention

  Number of participants with AEs leading to discontinuation of study intervention were reported.

  Induction Period: From induction Week 0 up to induction Week 8; Maintenance Period: From Maintenance Week 0 (Study Week 8) up to Maintenance Week 40 (Study Week 48)

• Global and US-specific Outcome Measures: Number of Participants With AEs of Special Interest (AESI)

  An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE did not necessarily have a causal relationship with the intervention. AESI were defined as any newly identified malignancy, or case of active TB, or opportunistic infection occurring after the first administration of study intervention.

  Induction Period: From induction Week 0 up to induction Week 8; Maintenance Period: From Maintenance Week 0 (Study Week 8) up to Maintenance Week 44 (Study Week 52)

• Global and US-specific Outcome Measures: Number of Participants With Abnormalities in Clinical Laboratory Parameters: Hematology

  Number of participants with abnormalities in clinical laboratory parameters (hematology) were reported. It included hemoglobin (Hb). Grades 0-4 were based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), where Grade 0 was normal, Grade 1 was mild, Grade 2 was moderate, Grade 3 was severe or medically significant but not immediately life-threatening, and Grade 4 was life-threatening consequences. Higher grades showed more severe abnormalities. Only abnormalities where atleast one participant had data are reported. Inc = increased, Dec= decreased.

  Induction Period: From induction Week 0 up to induction Week 8; Maintenance Period: From Maintenance Week 0 (Study Week 8) up to Maintenance Week 44 (Study Week 52)

• Global and US-specific Outcome Measures: Number of Participants With Abnormalities in Clinical Laboratory Parameters: Chemistry

  Number of participants with abnormalities in clinical laboratory parameters were reported. It included chemistry measures: alanine aminotransferase (ALT), aspartate aminotransferase (AST),blood bilirubin (BB). Grades 0-4 were based on NCI-CTCAE version 5.0, where Grade 0 was Normal, Grade 1 was mild, Grade 2 was moderate, Grade 3 was severe or medically significant but not immediately life-threatening, and Grade 4 was life-threatening consequences. Higher grades showed more severe abnormalities. Only abnormalities where at least one participant had data are reported. Inc = increased, Dec= decreased.

  Induction Period: From induction Week 0 up to induction Week 8; Maintenance Period: From Maintenance Week 0 (Study Week 8) up to Maintenance Week 44 (Study Week 52)

• Global and US-specific Outcome Measures: Number of Participants With Reactions Temporally Associated With Intravenous (IV) Infusion (Induction Period) and Subcutaneous (SC) Injection-Site Reactions (Maintenance Period)

  Number of participants with reactions temporally associated with intravenous (IV) infusion (Induction Period) and subcutaneous (SC) Injection-Site Reactions (Maintenance Period) were reported.

  Induction Period: From induction Week 0 up to induction Week 8; Maintenance Period: From Maintenance Week 0 (Study Week 8) up to Maintenance Week 44 (Study Week 52)

• Global and US-specific Outcome Measures: Serum Ustekinumab Concentrations

  Serum ustekinumab concentrations were reported.

  Induction Period: Week 0 (Pre-infusion), Week I-0 (1-hour post infusion), Week I-3, Week I-6, and Week I-8; Maintenance Period: Week M-4, Week M-8, Week M-12, Week M-16, Week M-24, Week M-32, Week M-36 and Week M-44

Secondary Outcomes (9)

• Global Outcome Measure: Percentage of Participants With Clinical Remission at Induction Week 6 as Assessed by Short Pediatric Crohn's Disease Activity Index (sPCDAI)

  Induction Week 6 (Week I-6)

• Global Outcome Measure: Percentage of Participants With Clinical Response at Induction Week 8

  Induction Week 8

• Global and US-specific Outcome Measures: Percentage of Participants With Clinical Response at Induction Week 6 as Assessed by sPCDAI

  Induction Week 6

• Global Outcome Measure: Percentage of Participants With Endoscopic Response at Maintenance Week 8 as Assessed by Simplified Endoscopic Score-Crohn's Disease (SES-CD)

  Maintenance Period Week 8 (Study Week 16)

• Global Outcome Measure: Percentage of Participants With Clinical Response at Maintenance Week 8

  Maintenance Week 8 (Study Week 16)

Study Arms (3)

Open- Label Ustekinumab Intravenous (IV): Induction Period

EXPERIMENTAL

All participants will receive a single IV administration of ustekinumab at induction Week 0 (I-0) based on body surface area (BSA) (milligram per meter square \[mg/m\^2\]) or weight-tiered induction dose (milligram per kilogram \[mg/kg\]).

Drug: Ustekinumab

Ustekinumab Subcutaneous (SC) Every 8 Weeks (q8w): Maintenance Period

EXPERIMENTAL

Participants will receive SC administration of ustekinumab q8w based on BSA (mg/m\^2) or weight-tiered induction dose (mg/kg) at maintenance weeks (Weeks M)-0, M-8, M-16, M-24, M 32, and M-40 and matching placebo at Weeks M-12 and M-36 to maintain the blind.

Drug: Ustekinumab; Drug: Placebo

Ustekinumab SC Every 12 Weeks (q12w): Maintenance Period

EXPERIMENTAL

Participants will receive SC administration of ustekinumab q12w based on BSA (mg/m\^2) or weight-tiered induction dose (mg/kg) at Weeks M-0, M-12, M-24, M-36 and matching placebo at Weeks M-8, M-16, M-32, and M-40 to maintain the blind.

Drug: Ustekinumab; Drug: Placebo

Interventions

Ustekinumab DRUG

Ustekinumab will be administered intravenously in induction period and subcutaneously in maintenance period.

Open- Label Ustekinumab Intravenous (IV): Induction Period; Ustekinumab SC Every 12 Weeks (q12w): Maintenance Period; Ustekinumab Subcutaneous (SC) Every 8 Weeks (q8w): Maintenance Period

Placebo DRUG

Matching placebo will be administered as SC injection.

Ustekinumab SC Every 12 Weeks (q12w): Maintenance Period; Ustekinumab Subcutaneous (SC) Every 8 Weeks (q8w): Maintenance Period

Eligibility Criteria

• Age: 2 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (53)

Nemours DuPont Hospital for Children

Wilmington, Delaware, 19803, United States

Location

Children's Center for Digestive Health Care

Atlanta, Georgia, 30342, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Morristown Memorial Hospital

Morristown, New Jersey, 07962, United States

Location

Levine Childrens at Atrium Health

Charlotte, North Carolina, 28207, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Penn State Hershey Children's Hospital

Hershey, Pennsylvania, 17033, United States

Location

Cook Childrens Medical Center

Fort Worth, Texas, 76104, United States

Location

Pediatric Specialists Of Virginia

Fairfax, Virginia, 22031, United States

Location

Universitair Kinderziekenhuis Koningin Fabiola

Brussels, 1020, Belgium

Location

Cliniques Universitaires Saint Luc

Brussels, 1200, Belgium

Location

UZ Gent

Ghent, 9000, Belgium

Location

UZ Brussel

Jette, 1090, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

Universitätsklinikum Aachen

Aachen, 52074, Germany

Location

Charite-Universitätsmedizin Berlin - Berlin

Berlin, 13353, Germany

Location

Universitatsklinikum Essen

Essen, 45147, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Dr. von Haunersches Kinderspital

Munich, 80337, Germany

Location

KUNO Klinik St. Hedwig

Regensburg, 93049, Germany

Location

Universitatsklinikum Ulm

Ulm, 89075, Germany

Location

Semmelweis Egyetem

Budapest, 1083, Hungary

Location

Debreceni Egyetem Klinikai Kozpont

Debrecen, 4032, Hungary

Location

Borsod Abauj Zemplen Varmegyei Kozponti Korhaz es Egyetemi Oktato Korhaz

Miskolc, 3526, Hungary

Location

Szabolcs Szatmar Bereg Varmegyei Oktatokorhaz

Nyíregyháza, 4400, Hungary

Location

Szegedi Tudományegyetem, Gyermekgyógyászati Klinika és Gyermekegészségügyi Centrum

Szeged, 6720, Hungary

Location

Yitzhak Shamir Medical Center

Be’er Ya‘aqov, 70300, Israel

Location

Carmel Medical Center

Haifa, 34362, Israel

Location

Shaare Zedek Medical Center

Jerusalem, 9103102, Israel

Location

Schneider Children's Medical Center

Petah Tikva, 4920235, Israel

Location

Juntendo University Hospital

Bunkyō City, 113 8431, Japan

Location

Gunma University Hospital

Gunma, 371-0034, Japan

Location

Kindai University Nara Hospital

Ikoma, 630-0293, Japan

Location

Kurume University Hospital

Kurume, 830-0011, Japan

Location

Saitama Childrens Medical Center

Saitama Shi, 330-8777, Japan

Location

Miyagi Children's Hospital

Sendai, 989-3126, Japan

Location

National Center for Child Health and Development

Setagaya Ku, 157 8535, Japan

Location

Jichi Medical University Hospital

Shimotsuke, 329-0498, Japan

Location

Mie University Hospital

Tsu, 514 8507, Japan

Location

Szpital im. M. Kopernika

Gdansk, 80 803, Poland

Location

Uniwersytecki Szpital Dzieciecy w Krakowie

Krakow, 30 663, Poland

Location

Korczowski Bartosz Gabinet Lekarski

Rzeszów, 35-302, Poland

Location

WIP Warsaw IBD Point Profesor Kierkus

Warsaw, 04 501, Poland

Location

Instytut Pomnik Centrum Zdrowia Dziecka

Warsaw, 04 730, Poland

Location

Kazan State Medical University

Kazan', 420138, Russia

Location

Russian National Research Medical University named after N.I.Pirogov

Moscow, 119571, Russia

Location

Privolzhsky Research Medical University of Ministry of Health of Russian Federation

Nizhny Novgorod, 603950, Russia

Location

Yaroslavl Regional Children's Clinical Hospital

Yaroslavl, 150032, Russia

Location

Birmingham Children's Hospital

Birmingham, B4 6NH, United Kingdom

Location

University Hospitals Bristol and Weston NHS Foundation Trust

Bristol, BS2 8BJ, United Kingdom

Location

Cambridge University Hospitals NHS Foundation Trust

Cambridge, CB2 0QQ, United Kingdom

Location

Royal Hospital for Children and Young People

Edinburgh, EH16 4TJ, United Kingdom

Location

Royal London Hospital

London, E1 2AT, United Kingdom

Location

Related Publications (1)

• De Greef E, Turner D, Kierkus J, Korczowski B, Meglicka M, Cohen SA, Hyams JS, Griffiths AM, Rosh JR, Strauss R, Van Limbergen E, Adedokun OJ, Kim L, Volger S; UNITI Jr study Group. Ustekinumab therapy for moderately to severely active pediatric Crohn's disease: UNITI Jr study safety and efficacy results in patients weighing at least 40 kg. J Crohns Colitis. 2026 Mar 10;20(3):jjag011. doi: 10.1093/ecco-jcc/jjag011.

  PMID: 41843763 DERIVED

MeSH Terms

Conditions

Crohn Disease

Interventions

Ustekinumab

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Assoc. Director Clinical Science Ped IM
• Organization: Janssen-Cilag International N.V.

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Induction period is an open-label period and maintenance period is a double-blind period.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 14, 2020
• First Posted: December 17, 2020
• Study Start: April 6, 2021
• Primary Completion: November 28, 2024
• Study Completion: March 3, 2025
• Last Updated: July 30, 2026
• Results First Posted: July 30, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share

Locations

IL (4); HU (5); BE (5); DE (7); JP (9); US (9); RU (4); PL (5); GB (5)