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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Crohn Disease

Intervention / Treatment
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* Drug: Ustekinumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 
| Number of Participants with Clinical Response | Number of participants with clinical response in induction period will be reported. | Week 8 (Induction period) | 
| 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) | 
| 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) | 
| Number of Participants with Clinical Response | Number of participants with clinical response in maintenance period will be reported. | Week 8 (Maintenance period) | 
| Number of Participants with Clinical Remission | Number of participants with clinical remission in maintenance period will be reported. | Week 44 (Maintenance period) | 
| 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) | 
| Number of Participants with Clinical Response | Number of participants with clinical response in maintenance period will be reported. | Week 44 (Maintenance period) | 
| 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) | 
| 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pediatric