A Study of Ustekinumab in Pediatric Participants With Moderately to Severely Active Ulcerative Colitis (UC)

Colitis, Ulcerative Clinical Trial

— UNIFI Jr  

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 Ulcerative Colitis

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04630028
• Other study ID #: CR108865
• Secondary ID: 2019-004224-38CN
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: March 17, 2021
• Est. completion date: November 7, 2025

Study information

• Verified date: June 2024
• 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: a) the efficacy of ustekinumab dosing in inducing clinical remission, b) safety profile of ustekinumab, and c) ustekinumab exposure (pharmacokinetics [PK]) in pediatric participants with moderately to severely active UC.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 113
• Est. completion date: November 7, 2025
• Est. primary completion date: July 24, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 17 Years

Eligibility

Inclusion Criteria:

• Medically stable on the basis of physical examination, medical history, and vital signs, performed at screening. Any abnormalities must be consistent with the underlying illness in the study population and this determination must be recorded in the participant's source documents and acknowledged by the investigator
• Must have had UC diagnosed prior to screening
• Have moderately to severely active UC, defined as a baseline Mayo score of 6 through 12, inclusive, with a screening Mayo endoscopy subscore greater than or equal to (>=) 2 as determined by a central review of the video of the endoscopy
• A participant who has had extensive colitis for >= 8 years, or disease limited to the left side of the colon for >= 10 years, must: a) have had a full colonoscopy to assess for the presence of dysplasia within 1 year before the first administration of study intervention or b) have a full colonoscopy with surveillance for dysplasia as the baseline endoscopy during the screening period. Results from these surveillance biopsies must be negative for dysplasia (low-grade, high-grade, or indeterminant) prior to the first administration of study intervention
• 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:

• Have UC limited to the rectum only or to less than (<) 20 centimeter (cm) of the colon
• Presence or history of colonic or small bowel obstruction within 6 months prior to screening, confirmed by objective radiographic or endoscopic evidence of a stricture with resulting obstruction (dilation of the colon or small bowel proximal to the stricture on barium radiograph or an inability to traverse the stricture at endoscopy)
• 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
• Has known allergies, hypersensitivity, or intolerance to ustekinumab or its excipients

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer

Intervention

Drug:
• Ustekinumab Dose Based on BSA and Body Weight
As per BSA and body weight Ustekinumab will be administered SC and IV.
• Matching Placebo
Placebo will be administered subcutaneously.

Locations

Country	Name	City	State
Belgium	Universitair Kinderziekenhuis Koningin Fabiola	Brussel
Belgium	Cliniques Universitaires Saint Luc	Bruxelles
Belgium	UZ Gent	Gent
Belgium	UZ Brussel	Jette
Belgium	UZ Leuven	Leuven
Germany	Universitätsklinikum Aachen	Aachen
Germany	Charite-Universitätsmedizin Berlin - Berlin	Berlin
Germany	Universitatsklinikum Erlangen	Erlangen
Germany	Universitatsklinikum Essen	Essen
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Dr. von Haunersches Kinderspital	Munich
Germany	KUNO Klinik St. Hedwig	Regensburg
Germany	Universitatsklinikum Ulm	Ulm
Hungary	Semmelweis Egyetem	Budapest
Hungary	Debreceni Egyetem Klinikai Kozpont	Debrecen
Hungary	Borsod-Abauj-Zemplen Varmegyei Kozponti Korhaz es Egyetemi Oktato Korhaz	Miskolc
Hungary	Szabolcs Szatmar Bereg Varmegyei Oktatokorhaz	Nyiregyhaza
Hungary	Szegedi Tudományegyetem, Gyermekgyógyászati Klinika és Gyermekegészségügyi Centrum	Szeged
Israel	Shamir Medical Center (Assaf Harofeh)	Be'er Ya'akov
Israel	Carmel Medical Center	Haifa
Israel	Rambam Medical Center	Haifa
Israel	Shaare Zedek Medical Center	Jerusalem
Israel	Schneider Children's Medical Center	Petah Tikva
Israel	Sheba Medical Center	Ramat Gan
Japan	Juntendo University Hospital	Bunkyo Ku
Japan	Gunma University Hospital	Gunma
Japan	Kindai University Nara Hospital	Ikoma
Japan	Kurume University Hospital	Kurume
Japan	Saitama Childrens Medical Center	Saitama shi
Japan	Miyagi Children's Hospital	Sendai
Japan	National Center for Child Health and Development	Setagaya Ku
Japan	Jichi Medical University Hospital	Shimotsuke
Japan	Mie University Hospital	Tsu
Poland	Szpital im. M. Kopernika	Gdansk
Poland	Uniwersytecki Szpital Dzieciecy w Krakowie	Krakow
Poland	Korczowski Bartosz Gabinet Lekarski	Rzeszow
Poland	GASTROMED Sp. z o.o.	Torun
Poland	Instytut Pomnik Centrum Zdrowia Dziecka	Warszawa
Poland	Medical Network	Warszawa
Russian Federation	Kazan State Medical University	Kazan
Russian Federation	FSBI 'Scientific Centre of Children Health' of the Russian Academy of Medical Sciences	Moscow
Russian Federation	Russian National Research Medical University named after N.I.Pirogov	Moscow
Russian Federation	Privolzhsky Research Medical University of Ministry of Health of Russian Federation	Nizhny Novgorod
Russian Federation	Saratov State Medical University	Saratov
Russian Federation	Yaroslavl Regional Children's Clinical Hospital	Yaroslavl
United Kingdom	Birmingham Children's Hospital	Birmingham
United Kingdom	University Hospitals Bristol and Weston NHS Foundation Trust	Bristol
United Kingdom	Cambridge University Hospitals NHS Foundation Trust	Cambridge
United Kingdom	Royal London Hospital	London
United States	Children's Center for Digestive Health Care	Atlanta	Georgia
United States	Levine Childrens at Atrium Health	Charlotte	North Carolina
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	Pediatric Specialists Of Virginia	Fairfax	Virginia
United States	Cook Childrens Medical Center	Fort Worth	Texas
United States	Penn State Hershey Children's Hospital	Hershey	Pennsylvania
United States	Morristown Memorial Hospital	Morristown	New Jersey
United States	Mayo Clinic	Rochester	Minnesota
United States	Nemours DuPont Hospital for Children	Wilmington	Delaware

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Belgium,  Germany,  Hungary,  Israel,  Japan,  Poland,  Russian Federation,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Global: Number of Participants with Clinical Remission at Induction Week 8 (I-8) Visit	Clinical remission is defined as Mayo stool frequency subscore of 0 or 1, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1 with no friability present on the endoscopy, where the stool frequency subscore has not increased from induction baseline.	Week 8
Primary	Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability	An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.	Up to 74 weeks
Primary	Number of Participants with Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability	SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect, and suspects transmission of any infectious agent via a medicinal product.	Up to 74 weeks
Primary	Number of Participants with AEs Leading to Discontinuation of Study Intervention	Number of Participants with discontinuation of study intervention due to an AE, infections, injection-site reactions, and AEs during or within 1 hour of an infusion will be reported.	Up to 74 weeks
Primary	Number of Participants with AEs of Special Interest (AESI) as a Measure of Safety and Tolerability	AESI of any newly identified malignancy, case of active tuberculosis (TB), or opportunistic infection occurring after the first administration of study intervention(s) in participants will be reported.	Up to 74 weeks
Primary	Number of Participants with Laboratory Abnormalities	Number of participants with laboratory abnormalities related to hematology, serum chemistry, and coagulation will be reported.	Up to 74 weeks
Primary	Reactions Temporally Associated with an Intravenous (IV) Infusion and Subcutaneous (SC) Injection-site Reactions	Reactions temporally associated with an IV infusion (induction period) and SC injection-site reactions (maintenance period) will be reported.	Up to 74 weeks
Primary	Serum Concentration of Ustekinumab	Serum samples will be analyzed to determine concentrations of ustekinumab.	Up to 74 weeks
Primary	US Specific: Clinical Remission at M-44 for Participants who are in Clinical Response at I-8	Clinical remission at M-44 for participants who are in clinical response at I-8 will be reported. Clinical remission is defined as a Mayo stool frequency subscore of 0 or 1, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1 with no friability present on the endoscopy, where the stool frequency subscore has not increased from induction baseline.	Week 52
Secondary	Number of Participants With Clinical Response at I-8 Visit	Clinical response is defined as decrease from baseline in the modified Mayo score by >= 30 percent (%) and >=2 points, with either a decrease from baseline in the rectal bleeding subscore of >= 1 or a rectal bleeding subscore of 0 or 1.	Week 8
Secondary	Number of Participants with Symptomatic Remission at I-8 Visit	Symptomatic remission is defined as Mayo stool frequency subscore of 0 or 1 and a rectal bleeding subscore of 0, where the stool frequency subscore has not increased from induction baseline.	Week 8
Secondary	Clinical Remission at I-8 as Assessed by the Pediatric Ulcerative Colitis Activity Index Score (PUCAI) Score	Clinical remission is defined as a PUCAI score less than (<)10.	Week 8
Secondary	Endoscopic Improvement at I-8 Visit	Endoscopic improvement is defined as a Mayo endoscopy subscore of 0 or <= 1 with no friability present on the endoscopy.	Week 8
Secondary	Histologic-endoscopic Mucosal Improvement at Week I-8	Histologic-endoscopic mucosal improvement is defined as achieving a combination of histologic (neutrophil infiltration in less than [<] 5% of crypts, no crypt destruction, and no erosions, ulcerations or granulation tissue according to the Geboes grading system) and endoscopic improvement (endoscopy subscore of 0 or 1 with no friability present on the endoscopy).	Week 8
Secondary	Number of Participants with Clinical Remission at Week 44 (M-44) Visit	Clinical remission is defined as a Mayo stool frequency subscore of 0 or 1, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1 with no friability present on the endoscopy, where the stool frequency subscore has not increased from induction baseline.	Week 52
Secondary	Number of Participants with Symptomatic Remission at M-44 Visit	Symptomatic remission is defined as Mayo stool frequency subscore of 0 or 1 and a rectal bleeding subscore of 0, where the stool frequency subscore has not increased from induction baseline.	Week 52
Secondary	Clinical Remission at M-44 as Assessed by the PUCAI Score	Clinical remission is defined as a PUCAI score less than < 10.	Week 52
Secondary	Endoscopic Improvement at M-44 Visit	Endoscopic improvement is defined as a Mayo endoscopy subscore of 0 or <= 1 with no friability present on the endoscopy.	Week 52
Secondary	Corticosteroid-free Clinical Remission at Week M-44	Corticosteroid-free clinical remission is defined as a Mayo stool frequency subscore of 0 or 1, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1 with no friability present on the endoscopy, where the stool frequency subscore has not increased from induction baseline; and not receiving corticosteroids for at least 90 days prior to Week M-44.	Week 52
Secondary	Clinical Remission at M-44 and not Receiving Corticosteroids for at Least 90 Days Prior to M-44 Among Participants who Received Corticosteroids at M-0	Clinical remission is defined as a PUCAI score less than < 10. Clinical remission at M-44 and in participants not receiving corticosteroids for at least 90 days prior to M-44 among participants who received corticosteroids at M-0 as assessed by PUCAI score will be reported.	Week 52
Secondary	Clinical Remission at M-44 for Participants who are in Clinical Remission at I-8	Clinical remission at M-44 for participants who are in clinical remission at I-8 will be reported. Clinical remission is defined as a Mayo stool frequency subscore of 0 or 1, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1 with no friability present on the endoscopy, where the stool frequency subscore has not increased from induction baseline.	Week 52
Secondary	US Specific: Number of Participants with Clinical Remission at I-8 Visit	Clinical remission is defined as Mayo stool frequency subscore of 0 or 1, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1 with no friability present on the endoscopy, where the stool frequency subscore has not increased from induction baseline.	Week 8
Secondary	Histologic-endoscopic Mucosal Improvement at Week M-44	Histologic-endoscopic mucosal improvement is defined as achieving a combination of histologic (neutrophil infiltration in < 5% of crypts, no crypt destruction, and no erosions, ulcerations or granulation tissue according to the Geboes grading system) and endoscopic improvement (endoscopy subscore of 0 or 1 with no friability present on the endoscopy).	Week 52