A Study of Guselkumab 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 clinical and endoscopic efficacy of guselkumab in pediatric participants with Crohn's Disease (CD) at the end of maintenance therapy (Week 52) among participants who were in clinical response to guselkumab at Week 12.

Detailed Description
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Participants screened in the MACARONI-23 platform study could be randomized to guselkumab to participate in this intervention specific arm of the study.

Official Title
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A Phase 3, Multicenter, Randomized, Platform Study of p19 Inhibition of the IL-23 Pathway to Establish Efficacy in Pediatric Crohn's Disease

Conditions
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Crohn's Disease

Intervention / Treatment
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* Drug: Guselkumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must have a diagnosis of Crohn's Disease (CD) or fistulizing CD, with active colitis, ileitis, or ileocolitis, confirmed at any time in the past by clinical, endoscopic, and histologic criteria. Participants must have moderately to severely active CD (as defined by a baseline Pediatric Crohn's Disease Activity Index [PCDAI] score greater than [>] 30) Participants must have endoscopy with evidence of active CD defined as Simple Endoscopic Score for Crohn's Disease (SES-CD) score greater than or equal to (>=) 6 (or >=4 for participants with isolated ileal disease) during screening into this study Participants must have a prior or current CD medication history that includes either inadequate response, loss of response to or failure to tolerate current treatment immunomodulators or with oral or intravenously (IV) corticosteroids or have received biologic therapy/JAK inhibitor for the treatment of CD and have a documented history of inadequate response, loss of response (LOR), or intolerance to the biologic therapy/JAK inhibitor Exclusion Criteria: Participants has complications of CD such as symptomatic strictures or stenosis, short gut syndrome, or any other manifestation that might be anticipated to require surgery. Participants must not have an abscess Participants must not have any kind of bowel resection within 26 weeks or any other intra-abdominal surgery within 12 weeks of baseline

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Open-label induction phase: Guselkumab Intravenously (IV)<br>Participants will receive guselkumab dose IV based on their body weight (BW) during the 12-week open-label induction phase. | Drug: Guselkumab<br>* Guselkumab will be administered either intravenously or subcutaneously.<br>* Other names: TREMFYA;|
| Experimental: Open-label induction phase: Guselkumab Subcutaneously (SC)<br>Participants will receive guselkumab dose SC based on their BW during the 12-week open-label induction phase. | Drug: Guselkumab<br>* Guselkumab will be administered either intravenously or subcutaneously.<br>* Other names: TREMFYA;|
| Experimental: Double-blind maintenance phase: Guselkumab SC or Guselkumab SC and Placebo SC<br>At the end of the induction phase, Week 12 responders will be randomized into the double-blind maintenance phase to receive a guselkumab dose SC based on their BW or a guselkumab dose SC based on their BW and placebo SC up to Week 48. | Drug: Guselkumab<br>* Guselkumab will be administered either intravenously or subcutaneously.<br>* Other names: TREMFYA;Drug: Placebo<br>* Week 12 induction responders will be administered placebo (matching guselkumab up to Week 48) SC at protocol specified time points to maintain the blind.<br>|
| Experimental: Open-label maintenance phase: Guselkumab SC<br>Week 12 non-responders will enter open-label maintenance phase to receive guselkumab SC dosing regimen based on their body weight up to Week 48. | Drug: Guselkumab<br>* Guselkumab will be administered either intravenously or subcutaneously.<br>* Other names: TREMFYA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with Clinical Remission at Week 52 | Percentage of participants with clinical remission at Week 52 will be assessed. Clinical remission is defined as pediatric Crohn's Disease activity index (PCDAI) less than or equal to (<=) 10. | Week 52 | 
| Percentage of Participants Who Achieve Endoscopic Response at Week 52 | Percentage of participants who achieve endoscopic response at Week 52 will be assessed. Endoscopic response is defined as greater than or equal to (>=) 50 percent (%) reduction from simplified endoscopic score-Crohn's Disease (SES-CD) score at baseline. | Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with Clinical Response at Week 12 | Percentage of participants with clinical response at Week 12 will be assessed. Clinical responder is defined as a decrease from baseline/loss of response (LOR) in the PCDAI score of >=12.5 points with a total PCDAI score <=30. | Week 12 | 
| Percentage of Participants with Clinical Response at Week 52 | Percentage of participants with clinical response at Week 52 will be assessed. Clinical responder is defined as a decrease from baseline/LOR in the PCDAI score of >=12.5 points with a total PCDAI score <=30. | Week 52 | 
| Percentage of Participants with Clinical Remission at Week 12 | Percentage of participants with clinical remission at Week 12 will be assessed. Clinical remission is defined as PCDAI score <=10. | Week 12 | 
| Percentage of Participants Who Achieve Endoscopic Response at Week 12 | Percentage of participants who achieve endoscopic response at Week 12 will be assessed. Endoscopic response is defined as >=50% reduction from SES-CD score at baseline. | Week 12 | 
| Percentage of Participants with Endoscopic Remission at Week 52 | Percentage of participants with endoscopic remission at Week 52 will be assessed. Endoscopic remission is defined as SES-CD total score <=4 and at least a 2-point reduction from baseline and no subscore >1. | Week 52 | 
| Percentage of Participants with Corticosteroid-free Remission at Week 52 | Percentage of participants with corticosteroid-free remission at Week 52 will be assessed. Corticosteroid-free remission is defined as PCDAI score <=10 at Week 52 and not receiving corticosteroids for at least 90 days before Week 52. | Week 52 | 
| Percentage of Participants with Sustained Clinical Remission at Weeks 12, 24, and 52 | Percentage of participants with sustained clinical remission at Weeks 12, 24, and 52 will be assessed. Sustained clinical remission is defined as PCDAI <=10 at Weeks 12, 24, and 52. | Weeks 12, 24, and 52 | 
| Percentage of Participants with Clinical remission by Patient-Reported Outcome (PRO) | Percentage of participants with clinical remission by PRO will be assessed. Clinical remission by PRO is defined as stool frequency (SF) <=3 and abdominal pain (AP) <=1 and no worsening of SF and AP from baseline. | Week 12 and/or Week 52 | 
| Serum Concentration of Guselkumab During Induction Phase | Serum concentrations of guselkumab will be assessed. Serum samples will be analyzed to determine concentrations of guselkumab using a validated, specific, and sensitive immunoassay method. | From Week 0 to Week 12 | 
| Trough Plasma Concentration (Ctrough) of Guselkumab During Maintenance Phase | Ctrough is defined as the serum concentration of guselkumab immediately prior (pre-dose) to the next drug administration. | At Weeks 16, 24, 36, 48 and 52 | 
| Change from Baseline in Body Weight at Weeks 12, 24, and 52 | Change from baseline in body weight at Weeks 12, 24, and 52 will be assessed. | Baseline, Weeks 12, 24, and 52 | 
| Change from Baseline in Body Weight Percentiles at Weeks 12, 24, and 52 | Change from baseline in body weight percentiles at Weeks 12, 24, and 52 will be assessed. | Baseline, Weeks 12, 24, and 52 | 
| Change from Baseline in Body Weight z-scores at Weeks 12, 24, and 52 | Change from baseline in body weight z-scores at Weeks 12, 24, and 52 will be assessed. | Baseline, Weeks 12, 24, and 52 | 
| Change from Baseline in Height at Weeks 12, 24, and 52 | Change from baseline in height at Weeks 12, 24, and 52 will be assessed. | Baseline, Weeks 12, 24, and 52 | 
| Change from Baseline in Height Percentiles at Weeks 12, 24, and 52 | Change from baseline in height percentiles at Weeks 12, 24, and 52 will be assessed. | Baseline, Weeks 12, 24, and 52 | 
| Change from Baseline in Height z-scores at Weeks 12, 24, and 52 | Change from baseline in height z-scores at Weeks 12, 24, and 52 will be assessed. | Baseline, Weeks 12, 24, and 52 | 
| Change from Baseline in Height Velocity at Weeks 12, 24, and 52 | Change from baseline in height velocity at Weeks 12, 24, and 52 will be assessed. | Baseline, Weeks 12, 24, and 52 | 
| Percentage of Participants with Clinical Remission | Percentage of participants with clinical remission who were assigned to q4w maintenance therapy and did not receive rescue therapy at Week 52 will be assessed. Clinical remission is defined as PCDAI score <=10. | Week 52 | 
| Percentage of Participants Who Achieve Endoscopic Response | Percentage of participants who achieve endoscopic response who were assigned to q4w maintenance therapy and did not receive rescue therapy at Week 52 will be assessed. Endoscopic response is defined as >=50% reduction from SES-CD score at baseline. | Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pediatric, Inflammatory bowel disease