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

NCT04673357 | Completed Phase 3 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)

• Number of Participants with Clinical Remission at Induction Week 8

  Number of participants with clinical remission in induction period will be assessed. Clinical remission is defined as having a Pediatric Crohn's Disease Activity Index (PCDAI) score less than or equal to (\<=) 10 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 8

• Number of Participants with Adverse Events (AEs)

  An AE can be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non investigational) product, whether or not related to that medicinal (investigational or non investigational) product.

  Up to Week 74

• Number of Participants with Serious Adverse Events (SAEs)

  A SAE is any untoward medical occurrence that at any dose: results in death; is life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is a suspected transmission of any infectious agent via a medicinal product; is medically important.

  Up to Week 74

• Number of Participants with AEs leading to Discontinuation of Study Intervention

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

  Up to Week 74

• Number of Participants with AEs of Interest

  Number of participants with AEs of interest (any newly identified malignancy, or case of active tuberculosis \[TB\], or opportunistic infection occurring after the first administration of study intervention\[s\]) will be reported.

  Up to Week 74

• Number of Participants with Abnormalities in Clinical Laboratory Parameters

  Number of participants with abnormalities in clinical laboratory parameters (such as hematology and chemistry) will be reported.

  Up to Week 52

• Number of Participants with Reactions Temporally Associated with Intravenous (IV) Infusion (Induction Period)

  Number of participants with reactions temporally associated with IV infusion in induction period will be reported.

  Up to Week 8 (Induction period)

• Number of Participants with Subcutaneous (SC) Injection-Site Reactions (Maintenance Period)

  Number of participants with SC injection-site reactions in maintenance period will be reported.

  Up to Week 44 (Maintenance period)

• Serum Ustekinumab Concentrations

  Serum ustekinumab concentrations will be reported.

  Up to Week 52

• Number of Participants with Clinical Remission at Maintenance Week 44

  Number of participants with clinical remission in maintenance period will be assessed. This will be assessed among participants who are in clinical response at induction week-8 (I-8). Clinical remission is defined as having a PCDAI score \<= 10 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 44 (Maintenance Period)

Secondary Outcomes (10)

• Number of Participants with Clinical Remission as Assessed by short Pediatric Crohn's Disease Activity Index (sPCDAI)

  Week 6 (Induction period)

• Number of Participants with Clinical Response

  Week 8 (Induction period)

• Number of Participants with Clinical Response as Assessed by sPCDAI

  Week 6 (Induction period)

• Number of Participants with Endoscopic Response as Assessed by Simplified Endoscopic Score-Crohn's Disease (SES-CD)

  Week 8 (Maintenance period)

• Number of Participants with Clinical Response

  Week 8 (Maintenance period)

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

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

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

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: November 28, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share

Locations

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