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

Crohn's Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05995353
• Other study ID #: M16-194
• Secondary ID: 2022-502050-14-0
• Status: Recruiting
• Phase: Phase 3
• Start date: December 11, 2023
• Est. completion date: April 28, 2029

Study information

• Verified date: May 2024
• Source: AbbVie
• Contact: ABBVIE CALL CENTER
• Phone: 844-663-3742
• Email: abbvieclinicaltrials[@]abbvie.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 110
• Est. completion date: April 28, 2029
• Est. primary completion date: April 28, 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 17 Years

Eligibility

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 (This drug class is not sufficient for eligibility for subjects in France, Italy, Netherlands, Spain, and Sweden), oral locally acting corticosteroids, systemic steroids (prednisone or equivalent), IMMs, and/or biologic therapies

Exclusion Criteria:

• History of hereditary fructose intolerance (a rare genetic condition) or 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:

1. Current diagnosis of ulcerative colitis, indeterminate colitis, or monogenic IBD.

2. A diagnosis of CD prior to 2 years of age.

3. A diagnosis or suspected diagnosis of a primary immunodeficiency.

4. 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.

5. Ostomy or ileoanal pouch.

6. Diagnosis of short gut or short bowel syndrome.

7. 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.

Related Conditions & MeSH terms

• Crohn Disease
• Crohn's Disease

Intervention

Drug:
• Risankizumab
Intravenous (IV) Infusion
• Risankizumab
Subcutaneous (SC) Injection

Locations

Country	Name	City	State
Israel	Shaare Zedek Medical Center /ID# 254951	Jerusalem	Yerushalayim
Israel	Schneider Children's Medical Center /ID# 254950	Petah Tikva	HaMerkaz
Korea, Republic of	Kyungpook National University Chilgok Hospital /ID# 255817	Daegu
Korea, Republic of	Samsung Medical Center /ID# 255284	Seoul
Korea, Republic of	Seoul National University Hospital /ID# 255318	Seoul
Korea, Republic of	Yonsei University Health System Severance Hospital /ID# 256976	Seoul	Seoul Teugbyeolsi
Puerto Rico	Puerto Rico Health Institute /ID# 255071	Dorado
Switzerland	Inselspital, Universitaetsspital Bern /ID# 255321	Bern
Switzerland	Kinderspital Zurich - Eleonorenstiftung /ID# 255337	Zurich	Zuerich
Taiwan	Changhua Christian Hospital /ID# 256082	Changhua City, Changhua County
Taiwan	National Taiwan University Hospital /ID# 255679	Taipei City	Taipei
United Kingdom	Barts Health NHS Trust /ID# 255757	London	London, City Of
United Kingdom	Sheffield Children's Hospital NHS Foundation Trust /ID# 255758	Sheffield	England
United States	Indiana University Health Riley Hospital for Children /ID# 256454	Indianapolis	Indiana
United States	Arkansas Children's Hospital /ID# 255762	Little Rock	Arkansas
United States	MNGI Digestive Health, P. A. /ID# 255366	Minneapolis	Minnesota
United States	Icahn School of Medicine at Mount Sinai /ID# 254880	New York	New York
United States	Arnold Palmer Hospital for Children Center Digestive Health & Nutrition - Orland /ID# 255437	Orlando	Florida

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

United States,  Israel,  Korea, Republic of,  Puerto Rico,  Switzerland,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	Cohorts 1 & 2: Maximum Observed Serum Concentration (Cmax) of Risankizumab	Cmax of risankizumab	Up to approximately Week 64
Primary	Cohorts 1 & 2: Time to Cmax (Tmax) of Risankizumab	Tmax of risankizumab	Up to approximately 64 weeks
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

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