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

• Sponsor: Janssen Research & Development, LLC (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04673357
• Collaborator: (none)
• Enrollment: 90
• Locations: 59
• Arms: 3
• Anticipated Duration (Months): 51.6
• Patients Per Site: 1.5
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Crohn Disease	Drug: Ustekinumab; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 90 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Masking Description: Induction period is an open-label period and maintenance period is a double-blind period.
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Apr 6, 2021
• Anticipated Primary Completion Date: Jul 24, 2025
• Anticipated Study Completion Date: Jul 25, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Open- Label Ustekinumab Intravenous (IV): Induction Period 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 will be administered intravenously in induction period and subcutaneously in maintenance period.
Experimental: Ustekinumab Subcutaneous (SC) Every 8 Weeks (q8w): Maintenance Period 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; Ustekinumab will be administered intravenously in induction period and subcutaneously in maintenance period.; Drug: Placebo; Matching placebo will be administered as SC injection.
Experimental: Ustekinumab SC Every 12 Weeks (q12w): Maintenance Period 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; Ustekinumab will be administered intravenously in induction period and subcutaneously in maintenance period.; Drug: Placebo; Matching placebo will be administered as SC injection.

Outcome Measures

Primary Outcome Measures

1. Number of Participants with Clinical Remission at Induction Week 8 [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.

2. Number of Participants with Adverse Events (AEs) [Up to Week 74]

   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.

3. Number of Participants with Serious Adverse Events (SAEs) [Up to Week 74]

   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.

4. Number of Participants with AEs leading to Discontinuation of Study Intervention [Up to Week 74]

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

5. Number of Participants with AEs of Interest [Up to Week 74]

   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.

6. Number of Participants with Abnormalities in Clinical Laboratory Parameters [Up to Week 52]

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

7. Number of Participants with Reactions Temporally Associated with Intravenous (IV) Infusion (Induction Period) [Up to Week 8 (Induction period)]

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

8. Number of Participants with Subcutaneous (SC) Injection-Site Reactions (Maintenance Period) [Up to Week 44 (Maintenance period)]

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

9. Serum Ustekinumab Concentrations [Up to Week 52]

   Serum ustekinumab concentrations will be reported.

10. Number of Participants with Clinical Remission at Maintenance Week 44 [Week 44 (Maintenance Period)]

    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.

Secondary Outcome Measures

1. 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 remission in induction period as assessed by sPCDAI will be reported. Clinical remission is defined as PCDAI score and sPCDAI score <= 10 points.

2. Number of Participants with Clinical Response [Week 8 (Induction period)]

   Number of participants with clinical response in induction period will be reported.

3. Number of Participants with Clinical Response as Assessed by sPCDAI [Week 6 (Induction period)]

   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.

4. 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 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).

5. Number of Participants with Clinical Response [Week 8 (Maintenance period)]

   Number of participants with clinical response in maintenance period will be reported.

6. Number of Participants with Clinical Remission [Week 44 (Maintenance period)]

   Number of participants with clinical remission in maintenance period will be reported.

7. Number of Participants with Endoscopic Response as Assessed by SES-CD [Week 44 (Maintenance period)]

   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).

8. Number of Participants with Clinical Response [Week 44 (Maintenance period)]

   Number of participants with clinical response in maintenance period will be reported.

9. Number of Participants with Corticosteroid-free Clinical Remission [Week 44 (Maintenance period)]

   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.

10. Number of Participants with Clinical Remission at Week 44 (Maintenance Period) who are in Clinical Remission at Week 8 (Induction Period) [Week 44 (Maintenance 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Nemours DuPont Hospital for Children	Wilmington	Delaware	United States	19803
2	Children's Center for Digestive Health Care	Atlanta	Georgia	United States	30342
3	Mayo Clinic	Rochester	Minnesota	United States	55905
4	Morristown Memorial Hospital	Morristown	New Jersey	United States	07962
5	Cohen Children's Medical Center	Lake Success	New York	United States	11042
6	Levine Children's at Atrium Health	Charlotte	North Carolina	United States	28207
7	University Hospitals Cleveland Medical Center	Cleveland	Ohio	United States	44106
8	Cleveland Clinic	Cleveland	Ohio	United States	44195
9	Penn State Hershey Children's Hospital	Hershey	Pennsylvania	United States	17033
10	Center For Digestive Health Systems-Greenville	Greenville	South Carolina	United States	29615
11	Children's Medical Center of Dallas	Dallas	Texas	United States	75390-9063
12	Cook Childrens Medical Center	Fort Worth	Texas	United States	76104
13	Pediatric Specialists Of Virginia	Fairfax	Virginia	United States	22031
14	Seattle Children's Hospital	Seattle	Washington	United States	98105
15	Universitair Kinderziekenhuis Koningin Fabiola	Brussel		Belgium	1020
16	Cliniques Universitaires Saint-Luc	Brussel		Belgium	1200
17	UZ Gent	Gent		Belgium	9000
18	UZ Brussel	Jette		Belgium	1090
19	UZ Leuven	Leuven		Belgium	3000
20	Universitätsklinikum Aachen	Aachen		Germany	52074
21	Charite-Universitätsmedizin Berlin - Berlin	Berlin		Germany	13353
22	Universitatsklinikum Essen	Essen		Germany	45147
23	Medizinische Hochschule Hannover	Hannover		Germany	30625
24	Dr. von Haunersches Kinderspital	Munich		Germany	80337
25	KUNO Klinik St. Hedwig	Regensburg		Germany	93049
26	Universitätsklinikum Ulm	Ulm		Germany	89075
27	Semmelweis Egyetem	Budapest		Hungary	1083
28	Debreceni Egyetem Klinikai Kozpont	Debrecen		Hungary	4032
29	Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Oktato Korhaz	Miskolc		Hungary	3526
30	Szabolcs-Szatmar-Bereg Megyei Korhazak es Egyetemi Oktatokorhaz, Josa Andras Oktatokorhaz	Nyiregyhaza		Hungary	4400
31	Szegedi Tudományegyetem, Gyermekgyógyászati Klinika és Gyermekegészségügyi Centrum	Szeged		Hungary	6720
32	Juntendo University Hospital	Bunkyo-Ku		Japan	113-8431
33	Gunma University Hospital	Gunma		Japan	371-0034
34	Kindai University Nara Hospital	Ikoma		Japan	630-0293
35	Osaka Women's and Children's Hospital	Izumi-shi, Osaka		Japan	594-1101
36	Kurume University Hospital	Kurume		Japan	830-0011
37	Aichi Children's Health and Medical Center	Obu		Japan	474-0031
38	Saitama Children's Medical Center	Saitama-shi		Japan	330-8777
39	Miyagi Children'S Hospital	Sendai-shi		Japan	989-3126
40	National Center for Child Health and Development	Setagaya-ku		Japan	157-8535
41	Jichi Medical University Hospital	Shimotsuke		Japan	329-0498
42	Mie University Hospital	Tsu		Japan	514-8507
43	Szpital im. M. Kopernika	Gdansk		Poland	80-803
44	Uniwersytecki Szpital Dzieciecy w Krakowie	Krakow		Poland	30-663
45	Gabinet Lekarski Bartosz Korczowski	Rzeszow		Poland	35-302
46	WIP Warsaw IBD Point Profesor Kierkus	Warszawa		Poland	00-728
47	Szpital Pomnik Centrum Zdrowia Dziecka	Warszawa		Poland	04-730
48	Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu	Wroclaw		Poland	50-369
49	Kazan State Medical University	Kazan		Russian Federation	420138
50	Russian National Research Medical University named after N.I.Pirogov	Moscow		Russian Federation	119571
51	FSBI 'Scientific Centre of Children Health' of the Russian Academy of Medical Sciences	Moscow		Russian Federation	119991
52	Privolzhsky Research Medical University of Ministry of Health of Russian Federation	Nizhny Novgorod		Russian Federation	603950
53	Saratov State Medical University	Saratov		Russian Federation	410054
54	Yaroslavl Regional Children's Clinical Hospital	Yaroslavl		Russian Federation	150032
55	Birmingham Children's Hospital	Birmingham		United Kingdom	B4 6NH
56	Cambridge University Hospitals NHS Foundation Trust	Cambridge		United Kingdom	CB2 0QQ
57	Royal Hospital for Children and Young People	Edinburgh		United Kingdom	EH16 4TJ
58	Royal London Hospital	London		United Kingdom	E1 2AT
59	King's College Hospital	London		United Kingdom	SE5 9RS

Sponsors and Collaborators

• Janssen Research & Development, LLC

Investigators

• Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Janssen Research & Development, LLC
• ClinicalTrials.gov Identifier: NCT04673357
• Other Study ID Numbers: CR108864; 2019-004225-24; CNTO1275CRD3004
• First Posted: Dec 17, 2020
• Last Update Posted: Aug 18, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Janssen Research & Development, LLC: Pediatric
• Additional relevant MeSH terms: Crohn Disease; Ustekinumab

Study Results

No Results Posted as of Aug 18, 2022