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

Crohn Disease Clinical Trial

— UNITI 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 Crohn's Disease

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04673357
• Other study ID #: CR108864
• Secondary ID: 2019-004225-24CN
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: April 6, 2021
• Est. completion date: July 25, 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 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 101
• Est. completion date: July 25, 2025
• Est. primary completion date: July 24, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Crohn Disease

Intervention

Drug:
• Ustekinumab
Ustekinumab will be administered intravenously in induction period and subcutaneously in maintenance period.
• Placebo
Matching placebo will be administered as SC injection.

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 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	Yitzhak Shamir Medical Center	Be'er Ya'akov
Israel	Carmel Medical Center	Haifa
Israel	Shaare Zedek Medical Center	Jerusalem
Israel	Schneider Children's Medical Center	Petah Tikva
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	Instytut Pomnik Centrum Zdrowia Dziecka	Warszawa
Poland	Medical Network	Warszawa
Russian Federation	Kazan State Medical University	Kazan
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	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 Hospital for Children and Young People	Edinburgh
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	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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)
Primary	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)
Primary	Serum Ustekinumab Concentrations	Serum ustekinumab concentrations will be reported.	Up to Week 52
Primary	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	Number of Participants with Clinical Remission as Assessed by short Pediatric Crohn's Disease Activity Index (sPCDAI)	Number of participants with clinical remission in induction period as assessed by sPCDAI will be reported. Clinical remission is defined as PCDAI score and sPCDAI score <= 10 points.	Week 6 (Induction period)
Secondary	Number of Participants with Clinical Response	Number of participants with clinical response in induction period will be reported.	Week 8 (Induction period)
Secondary	Number of Participants with Clinical Response as Assessed by sPCDAI	Number of participants with clinical response in induction period as assessed by sPCDAI will be reported. Clinical response is defined as a reduction from baseline in the PCDAI score of greater than or equal to (>=) 12.5 points with a total PCDAI score not more than 30.	Week 6 (Induction period)
Secondary	Number of Participants with Endoscopic Response as Assessed by Simplified Endoscopic Score-Crohn's Disease (SES-CD)	Number of participants with endoscopic response as assessed by SES-CD in maintenance period will be reported. Endoscopic response is defined as a reduction in SES-CD score of >= 50 percent (%) or SES-CD score <= 2 in participants with a baseline SES-CD score of >= 3. The SES-CD score is based on the evaluation of 4 endoscopic components (presence/size of ulcers, proportion of mucosal surface covered by ulcers, proportion of mucosal surface affected by any other lesions, and presence/type of narrowing/strictures) across 5 ileocolonic segments. Each endoscopic component is scored from 0 to 3 for each segment, and a total score is derived from the sum of all the component scores (range, 0 to 60).	Week 8 (Maintenance period)
Secondary	Number of Participants with Clinical Response	Number of participants with clinical response in maintenance period will be reported.	Week 8 (Maintenance period)
Secondary	Number of Participants with Clinical Remission	Number of participants with clinical remission in maintenance period will be reported.	Week 44 (Maintenance period)
Secondary	Number of Participants with Endoscopic Response as Assessed by SES-CD	Number of participants with endoscopic response as assessed by SES-CD in maintenance period will be reported. Endoscopic response is defined as a reduction in SES-CD score of >= 50 percent (%) or SES-CD score <= 2 in participants with a baseline SES-CD score of >= 3. The SES-CD score is based on the evaluation of 4 endoscopic components (presence/size of ulcers, proportion of mucosal surface covered by ulcers, proportion of mucosal surface affected by any other lesions, and presence/type of narrowing/strictures) across 5 ileocolonic segments. Each endoscopic component is scored from 0 to 3 for each segment, and a total score is derived from the sum of all the component scores (range, 0 to 60).	Week 44 (Maintenance period)
Secondary	Number of Participants with Clinical Response	Number of participants with clinical response in maintenance period will be reported.	Week 44 (Maintenance period)
Secondary	Number of Participants with Corticosteroid-free Clinical Remission	Number of participants with corticosteroid-free clinical remission in maintenance period will be reported. Corticosteroid-free clinical remission is PCDAI score <= 10 points and not receiving corticosteroids for at least 90 days prior to Week 44.	Week 44 (Maintenance period)
Secondary	Number of Participants with Clinical Remission at Week 44 (Maintenance Period) who are in Clinical Remission at Week 8 (Induction Period)	Number of participants with clinical remission at Week 44 (maintenance period) who are in clinical remission at Week 8 (induction period) will be reported.	Week 44 (Maintenance Period)