A Study to Assess Adverse Events, Change in Disease Activity, and How Intravenous and Subcutaneous Risankizumab Moves Through the Body of Pediatric Participants With Moderately to Severely Active Crohn's Disease

Study Overview
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Brief Summary
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Crohn's Disease (CD) is a gastrointestinal disease that can cause chronic diarrhea with or without gross bleeding, abdominal pain, weight loss, and fever. This study will assess the pharmacokinetics, efficacy, and safety of risankizumab in pediatric participants with moderately to severely active CD aged 2 to < 18 years old who have had intolerance or inadequate response to other therapies. Risankizumab is an approved drug for adults with plaque psoriasis, psoriatic arthritis, and CD and is being developed for the treatment of CD in pediatrics. This study is comprised of 3 cohorts that may participate in 3 substudies (SS). Cohort 1 will enroll participants with ages from 6 to less than 18 years. Cohort 2 will enroll participants with ages from 2 to less than 6 years. Cohort 3 will enroll participants with ages from 2 to less than 18 years. SS1 is an open-label induction period where participants will receive a weight-based induction regimen of risankizumab. SS2 is a double-blind maintenance period where participants will be randomized to receive 1 of 2 doses of weight-based induction regimen of risankizumab. SS3 is an open-label extension period where participants will receive risankizumab based off of their response in SS2. Around 110 pediatric participants with CD will be enrolled at around 100 sites worldwide. Participants in SS1 will receive risankizumab intravenously during the 12-week induction period. Participants in SS2 will receive risankizumab subcutaneously during the 52-week randomized maintenance period. Participants in SS3 will receive risankizumab subcutaneously during the 208-week open label period. Participants will be followed-up for approximately 140 days. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.

Official Title
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A Phase 3, Multi-Center Study to Evaluate the Pharmacokinetics, Efficacy, and Safety of Risankizumab With Open-Label Induction, Randomized Double-Blind Maintenance, and Long-Term Extension Periods in Pediatric Subjects (2 to < 18 Years of Age) With Moderately to Severely Active Crohn's Disease

Conditions
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Crohn's Disease

Intervention / Treatment
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* Drug: Risankizumab
* Drug: Risankizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pediatric individuals, 2 to < 18 years old Must have moderately to severely active CD, as defined by the PCDAI score > 30 assessed at Baseline Must have endoscopic evidence of mucosal inflammation as documented by the SES-CD of ≥ 6 for ileocolonic or colonic disease (or SES-CD of ≥ 4 for isolated ileal disease) Demonstrated intolerance or inadequate response to one or more of the following categories of drugs: aminosalicylates, oral locally acting corticosteroids, systemic steroids (prednisone or equivalent), IMMs, and/or biologic therapies Exclusion Criteria: History of an allergic reaction or significant sensitivity to constituents of the study drug (and its excipients) and/or other products in the same class Any of the following medical disorders: Current diagnosis of ulcerative colitis, indeterminate colitis, or monogenic IBD. A diagnosis of CD prior to 2 years of age. A diagnosis or suspected diagnosis of a primary immunodeficiency. Currently known complications of CD such as: Active abscess (abdominal or perianal); Symptomatic bowel strictures; > 2 missing segments of the following 5 segments: terminal ileum, right colon, transverse colon, sigmoid and left colon, and rectum; Fulminant colitis; Toxic megacolon; Or any other manifestation that might require surgery while enrolled in the study. Ostomy or ileoanal pouch. Diagnosis of short gut or short bowel syndrome. Surgical bowel resection within the past 3 months prior to Baseline (excluding gastrointestinal surgeries which are not bowel resections such as appendectomy or ostomy closure), or a history of >3 bowel resections.

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: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PK Cohort 1: SS1<br>Cohort 1 will consist of 2 age groups (6 to < 12 years and 12 to < 18 years). SS1 is a 12-week induction period where participants will receive a weight-based dose of risankizumab. All subjects who complete SS1 are eligible to enter SS2. | Drug: Risankizumab<br>* Intravenous (IV) Infusion<br>* Other names: SKYRIZI;|
| Experimental: PK Cohort 1: SS2 Dose A<br>Cohort 1 will consist of 2 age groups (6 to < 12 years and 12 to < 18 years). Participants who complete SS1 will be randomized into a 52-week maintenance phase (SS2) to receive double-blind risankizumab Dose A. Participants who complete SS2 will have the opportunity to enter the open-label long-term-extension SS3. | Drug: Risankizumab<br>* Subcutaneous (SC) Injection<br>* Other names: SKYRIZI;|
| Experimental: PK Cohort 1: SS2 Dose B<br>Cohort 1 will consist of 2 age groups (6 to < 12 years and 12 to < 18 years). Participants who complete SS1 will be randomized into a 52-week maintenance phase (SS2) to receive double-blind risankizumab Dose B. Participants who complete SS2 will have the opportunity to enter the open-label long-term-extension SS3. | Drug: Risankizumab<br>* Subcutaneous (SC) Injection<br>* Other names: SKYRIZI;|
| Experimental: PK Cohort 1: SS3 Dose A<br>Cohort 1 will consist of 2 age groups (6 to < 12 years and 12 to < 18 years). SS3 is a 208-week extension period where participants receive risankizumab based on their response in SS2. | Drug: Risankizumab<br>* Subcutaneous (SC) Injection<br>* Other names: SKYRIZI;|
| Experimental: PK Cohort 1: SS3 Dose B<br>Cohort 1 will consist of 2 age groups (6 to < 12 years and 12 to < 18 years). SS3 is a 208-week extension period where participants receive risankizumab based on their response in SS2. | Drug: Risankizumab<br>* Subcutaneous (SC) Injection<br>* Other names: SKYRIZI;|
| Experimental: PK Cohort 2: SS1<br>Cohort 2 will enroll participants aged 2 to less than 6 years. SS1 is a 12-week induction period where participants will receive a weight-based dose of risankizumab. All subjects who complete SS1 are eligible to enter SS2. | Drug: Risankizumab<br>* Intravenous (IV) Infusion<br>* Other names: SKYRIZI;|
| Experimental: PK Cohort 2: SS2 Dose A<br>Cohort 2 will enroll participants aged 2 to less than 6 years. Participants who complete SS1 will be randomized into a 52-week maintenance phase (SS2) to receive double-blind risankizumab Dose A. Participants who complete SS2 will have the opportunity to enter the open-label long-term-extension SS3. | Drug: Risankizumab<br>* Subcutaneous (SC) Injection<br>* Other names: SKYRIZI;|
| Experimental: PK Cohort 2: SS2 Dose B<br>Cohort 2 will enroll participants aged 2 to less than 6 years. Participants who complete SS1 will be randomized into a 52-week maintenance phase (SS2) to receive double-blind risankizumab Dose B. Participants who complete SS2 will have the opportunity to enter the open-label long-term-extension SS3. | Drug: Risankizumab<br>* Subcutaneous (SC) Injection<br>* Other names: SKYRIZI;|
| Experimental: PK Cohort 2: SS3 Dose A<br>Cohort 2 will enroll participants aged 2 to less than 6 years. SS3 is a 208-week extension period where participants receive risankizumab based on their response in SS2. | Drug: Risankizumab<br>* Subcutaneous (SC) Injection<br>* Other names: SKYRIZI;|
| Experimental: PK Cohort 2: SS3 Dose B<br>Cohort 2 will enroll participants aged 2 to less than 6 years. SS3 is a 208-week extension period where participants receive risankizumab based on their response in SS2. | Drug: Risankizumab<br>* Subcutaneous (SC) Injection<br>* Other names: SKYRIZI;|
| Experimental: Expansion Cohort 3: SS1<br>Cohort 3 will enroll participants aged 2 to less than 18 years. SS1 is a 12-week induction period where participants will receive a weight-based dose of risankizumab. All subjects who complete SS1 are eligible to enter SS2. | Drug: Risankizumab<br>* Intravenous (IV) Infusion<br>* Other names: SKYRIZI;|
| Experimental: Expansion Cohort 3: SS2 Dose A<br>Cohort 3 will enroll participants aged 2 to less than 18 years. Participants who complete SS1 will be randomized into a 52-week maintenance phase (SS2) to receive either double-blind risankizumab Dose A. Participants who complete SS2 will have the opportunity to enter the open-label long-term-extension SS3. | Drug: Risankizumab<br>* Subcutaneous (SC) Injection<br>* Other names: SKYRIZI;|
| Experimental: Expansion Cohort 3: SS2 Dose B<br>Cohort 3 will enroll participants aged 2 to less than 18 years. Participants who complete SS1 will be randomized into a 52-week maintenance phase (SS2) to receive either double-blind risankizumab Dose B. Participants who complete SS2 will have the opportunity to enter the open-label long-term-extension SS3. | Drug: Risankizumab<br>* Subcutaneous (SC) Injection<br>* Other names: SKYRIZI;|
| Experimental: Expansion Cohort 3: SS3 Dose A<br>Cohort 3 will enroll participants aged 2 to less than 18 years. SS3 is a 208-week extension period where participants receive risankizumab based on their response in SS2. | Drug: Risankizumab<br>* Subcutaneous (SC) Injection<br>* Other names: SKYRIZI;|
| Experimental: Expansion Cohort 3: SS3 Dose B<br>Cohort 3 will enroll participants aged 2 to less than 18 years. SS3 is a 208-week extension period where participants receive risankizumab based on their response in SS2. | Drug: Risankizumab<br>* Subcutaneous (SC) Injection<br>* Other names: SKYRIZI;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohort 3 (Substudy 2): Percentage of Participants Achieving Pediatric Crohn's Disease Activity Index (PCDAI) Clinical Remission | 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, abdomen, perirectal disease, and extraintestinal manifestations. It ranges from 0 to 100; higher scores indicate more active disease. Clinical remission was defined as PCDAI ≤ 10. | At 64 weeks | 
| Cohort 3 (Substudy 2): Percentage of Participants Achieving Endoscopic Response per Simple Endoscopic Score for Crohn's Disease (SES-CD) | The SES-CD assesses endoscopic disease severity by evidence of active intestinal mucosal inflammation. Endoscopic response is defined as a decrease in SES-CD > 50% from Baseline (or for participants with isolated ileal disease and a Baseline SES-CD of 4, at least a 2-point reduction from Baseline). | At 64 weeks | 
| Cohorts 1 & 2: Maximum Observed Serum Concentration (Cmax) of Risankizumab | Cmax of risankizumab | Up to approximately Week 64 | 
| Cohorts 1 & 2: Time to Cmax (Tmax) of Risankizumab | Tmax of risankizumab | Up to approximately 64 weeks | 
| Cohorts 1 & 2: Area Under the Serum Concentration-Time Curve Over the Dosing Interval (AUCtau) of Risankizumab | AUCtau of risankizumab | Up to approximately 64 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohort 3 (Substudy 1): Percentage of Participants Achieving PCDAI Clinical Remission | 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, abdomen, perirectal disease, and extraintestinal manifestations. It ranges from 0 to 100; higher scores indicate more active disease. Clinical remission was defined as PCDAI ≤ 10. | At 12 weeks | 
| Cohort 3 (Substudy 1): Percentage of Participants Achieving Endoscopic Response per SES-CD | The SES-CD assesses endoscopic disease severity by evidence of active intestinal mucosal inflammation. Endoscopic response is defined as a decrease in SES-CD > 50% from Baseline (or for participants with isolated ileal disease and a Baseline SES-CD of 4, at least a 2-point reduction from Baseline). | At 12 weeks | 
| Cohort 3 (Substudy 1): Percentage of Participants Achieving Endoscopic Remission per SES-CD | The SES-CD assesses endoscopic disease severity by evidence of active intestinal mucosal inflammation. Endoscopic remission is defined as SES-CD ≤ 4 with at least a 2-point reduction from Baseline and no sub-score > 1, as scored by a central reader. | At 12 weeks | 
| Cohort 3 (Substudy 2): Percentage of Participants Achieving Endoscopic Remission per SES-CD | The SES-CD assesses endoscopic disease severity by evidence of active intestinal mucosal inflammation. Endoscopic remission is defined as SES-CD ≤ 4 with at least a 2-point reduction from Baseline and no sub-score > 1, as scored by a central reader. | At 64 weeks | 
| Cohort 3 (Substudy 2): Percentage of Participants Achieving Corticosteroid-Free Clinical Remission per PCDAI | 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, abdomen, perirectal disease, and extraintestinal manifestations. It ranges from 0 to 100; higher scores indicate more active disease. PCDAI corticosteroid-free remission was defined as discontinued corticosteroid use at least 90 consecutive days prior to the respective visit, with a PCDAI ≤ 10 at that visit. | At 64 weeks | 
| Cohorts 1 & 2 (Substudy 2): Percentage of Participants Achieving PCDAI Clinical Remission | 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, abdomen, perirectal disease, and extraintestinal manifestations. It ranges from 0 to 100; higher scores indicate more active disease. Clinical remission was defined as PCDAI ≤ 10. | At 64 weeks | 
| Cohorts 1 & 2 (Substudy 2): Percentage of Participants Achieving Endoscopic Response per SES-CD | The SES-CD assesses endoscopic disease severity by evidence of active intestinal mucosal inflammation. Endoscopic response is defined as a decrease in SES-CD > 50% from Baseline (or for participants with isolated ileal disease and a Baseline SES-CD of 4, at least a 2-point reduction from Baseline). | At 64 weeks | 
| Cohorts 1 & 2 (Substudy 1): Percentage of Participants Achieving PCDAI Clinical Remission | 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, abdomen, perirectal disease, and extraintestinal manifestations. It ranges from 0 to 100; higher scores indicate more active disease. Clinical remission was defined as PCDAI ≤ 10. | At 12 weeks | 
| Cohorts 1 & 2 (Substudy 1): Percentage of Participants Achieving Endoscopic Response per SES-CD | The SES-CD assesses endoscopic disease severity by evidence of active intestinal mucosal inflammation. Endoscopic response is defined as a decrease in SES-CD > 50% from Baseline (or for participants with isolated ileal disease and a Baseline SES-CD of 4, at least a 2-point reduction from Baseline). | At 12 weeks | 
| Cohorts 1 & 2 (Substudy 1): Percentage of Participants Achieving Endoscopic Remission per SES-CD | The SES-CD assesses endoscopic disease severity by evidence of active intestinal mucosal inflammation. Endoscopic remission is defined as SES-CD ≤ 4 with at least a 2-point reduction from Baseline and no sub-score > 1, as scored by a central reader. | At 12 weeks | 
| Cohorts 1 & 2 (Substudy 2): Percentage of Participants Achieving Endoscopic Remission per SES-CD | The SES-CD assesses endoscopic disease severity by evidence of active intestinal mucosal inflammation. Endoscopic remission is defined as SES-CD ≤ 4 with at least a 2-point reduction from Baseline and no sub-score > 1, as scored by a central reader. | At 64 weeks | 
| Cohorts 1 & 2 (Substudy 2): Percentage of Participants Achieving Corticosteroid-Free Clinical Remission per PCDAI | 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, abdomen, perirectal disease, and extraintestinal manifestations. It ranges from 0 to 100; higher scores indicate more active disease. PCDAI corticosteroid-free remission was defined as discontinued corticosteroid use at least 90 consecutive days prior to the respective visit, with a PCDAI ≤ 10 at that visit. | At 64 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Skyrizi, Crohn's Disease, Risankizumab, Pediatrics