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

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

Overview

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. Approximately 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.

Interventions

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

Primary outcome measures

• Cohort 3 (Substudy 2): Percentage of Participants Achieving Pediatric Crohn's Disease Activity Index (PCDAI) Clinical Remission [Time frame: At 64 weeks]
• Cohort 3 (Substudy 2): Percentage of Participants Achieving Endoscopic Response per Simple Endoscopic Score for Crohn's Disease (SES-CD) [Time frame: At 64 weeks]
• Cohorts 1 & 2: Maximum Observed Serum Concentration (Cmax) of Risankizumab [Time frame: Up to approximately Week 64]
• Cohorts 1 & 2: Time to Cmax (Tmax) of Risankizumab [Time frame: Up to approximately 64 weeks]
• Cohorts 1 & 2: Area Under the Serum Concentration-Time Curve Over the Dosing Interval (AUCtau) of Risankizumab [Time frame: Up to approximately 64 weeks]

Secondary outcome measures (12)

• Cohort 3 (Substudy 1): Percentage of Participants Achieving PCDAI Clinical Remission [Time frame: At 12 weeks]
• Cohort 3 (Substudy 1): Percentage of Participants Achieving Endoscopic Response per SES-CD [Time frame: At 12 weeks]
• Cohort 3 (Substudy 1): Percentage of Participants Achieving Endoscopic Remission per SES-CD [Time frame: At 12 weeks]
• Cohort 3 (Substudy 2): Percentage of Participants Achieving Endoscopic Remission per SES-CD [Time frame: At 64 weeks]
• Cohort 3 (Substudy 2): Percentage of Participants Achieving Corticosteroid-Free Clinical Remission per PCDAI [Time frame: At 64 weeks]
• Cohorts 1 & 2 (Substudy 2): Percentage of Participants Achieving PCDAI Clinical Remission [Time frame: At 64 weeks]
• Cohorts 1 & 2 (Substudy 2): Percentage of Participants Achieving Endoscopic Response per SES-CD [Time frame: At 64 weeks]
• Cohorts 1 & 2 (Substudy 1): Percentage of Participants Achieving PCDAI Clinical Remission [Time frame: At 12 weeks]
• Cohorts 1 & 2 (Substudy 1): Percentage of Participants Achieving Endoscopic Response per SES-CD [Time frame: At 12 weeks]
• Cohorts 1 & 2 (Substudy 1): Percentage of Participants Achieving Endoscopic Remission per SES-CD [Time frame: At 12 weeks]
• Cohorts 1 & 2 (Substudy 2): Percentage of Participants Achieving Endoscopic Remission per SES-CD [Time frame: At 64 weeks]
• Cohorts 1 & 2 (Substudy 2): Percentage of Participants Achieving Corticosteroid-Free Clinical Remission per PCDAI [Time frame: At 64 weeks]

Eligibility criteria

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:

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Sequential

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 11 centers

• Phoenix Children's Hospital /ID# 255766 — Phoenix
• Arkansas Children's Hospital /ID# 255762 — Little Rock
• UCSF Benioff Children's Hospital - Oakland /ID# 258327 — Oakland
• Children's Hospital Colorado - Aurora /ID# 255764 — Aurora
• Arnold Palmer Hospital for Children Center Digestive Health and Nutrition-Orland /ID# 2554 — Orlando
• Indiana University Health Riley Hospital for Children /ID# 256454 — Indianapolis
• Massachusetts General Hospital /ID# 255767 — Boston
• MNGI Digestive Health, P. A. /ID# 255366 — Minneapolis
• … and 3 more centers

China · 10 centers

• Beijing Children's Hospital /ID# 256081 — Beijing
• Peking University Third Hospital /ID# 255876 — Beijing
• Guangzhou Medical University Affiliated Women and Children's Medical Center /ID# 255428 — Guangzhou
• The Sixth Affiliated Hospital of Sun Yat-sen University /ID# 270589 — Guangzhou
• Henan Children's Hospital Zhengzhou Children's Hospital /ID# 255562 — Zhengzhou
• Hunan Children's Hospital /ID# 255610 — Changsha
• Jiangxi Provincial Children's Hospital /ID# 255564 — Nanchang
• Shengjing Hospital of China Medical University /ID# 255563 — Shenyang
• … and 2 more centers

Japan · 10 centers

• Aichi Children'S Health And Medical Center /ID# 272085 — Ōbu
• Tsujinaka Hospital - Kashiwanoha /ID# 268409 — Kashiwa-shi
• Kurume University Hospital /ID# 268418 — Kurume-shi
• Gunma University Hospital /ID# 270560 — Maebashi
• Japanese Red Cross Kumamoto Hospital /ID# 268586 — Kumamoto
• Osaka Women's and Children's Hospital /ID# 268419 — Izumi-Shi
• Saitama Children's Medical Center /ID# 268410 — Saitama-shi
• Institute of Science Tokyo Hospital /ID# 269175 — Bunkyo-ku
• … and 2 more centers

Belgium · 6 centers

• Uza /Id# 255114 — Edegem
• Cliniques Universitaires UCL Saint-Luc /ID# 255108 — Brussels
• Universitair Ziekenhuis Brussel /ID# 255109 — Jette
• Groupe Sante CHC - Clinique du MontLegia /ID# 255620 — Liège
• Universitair Ziekenhuis Leuven /ID# 255098 — Leuven
• Hospital Universite Enfants Reine Fabiola /ID# 255112 — Brussels

France · 5 centers

• CHRU Tours - Hopital Gatien de Clocheville /ID# 255052 — Tours
• CHU Bordeaux - Hopital Pellegrin /ID# 257060 — Bordeaux
• CHU Toulouse - Hopital Paule de Viguier /ID# 255609 — Toulouse
• Hospices Civils de Lyon - Hôpital Femme Mère Enfant /ID# 255443 — Bron
• AP-HP - Hopital Necker /ID# 255608 — Paris

Canada · 4 centers

• Alberta Children's Hospital /ID# 255357 — Calgary
• Edmonton Clinic Health Academy /ID# 255361 — Edmonton
• BC Children's Hospital /ID# 255359 — Vancouver
• London Health Sciences Centre - Victoria Hospital & Children's Hospital /ID# 258598 — London

Italy · 4 centers

• IRCCS Istituto Giannina Gaslini /ID# 255262 — Genoa
• Azienda Ospedaliera Universitaria Federico II - Naples /ID# 255045 — Naples
• Ospedale Pediatrico Bambino Gesù /ID# 255043 — Rome
• Azienda Ospedaliera Universitaria Gaetano Martino /ID# 255044 — Messina

South Korea · 4 centers

• Seoul National University Hospital /ID# 255318 — Seoul
• Yonsei University Health System Severance Hospital /ID# 256976 — Seoul
• Samsung Medical Center /ID# 255284 — Seoul
• Kyungpook National University Chilgok Hospital /ID# 255817 — Daegu

Turkey (Türkiye) · 4 centers

• Gazi University Medical Faculty /ID# 255086 — Ankara
• Sariyer Hamidiye Etfal Eğitim Ve Araştirma Hastanesi /ID# 257143 — Istanbul
• … and 2 more centers

Bulgaria · 3 centers

• UMHAT Sveti Georgi /ID# 255386 — Plovdiv
• Specialized Hospital For Active Treatment Of Children Diseases Prof. Ivan Mitev /ID# 25538 — Sofia
• UMHAT Multiprofile Hospital for Active Treatment Sveta Marina /ID# 256358 — Varna

Spain · 3 centers

• Hospital Arquitecto Marcide - Complejo Hospitalario Universitario de Ferrol /ID# 255614 — Ferrol
• Hospital Infantil Universitario Nino Jesus /ID# 255012 — Madrid
• Hospital Regional Universitario de Malaga /ID# 257553 — Málaga

Sweden · 3 centers

• Sodersjukhuset /ID# 255239 — Stockholm
• Astrid Lindgrens Barnsjukhus /ID# 255240 — Stockholm
• Sahlgrenska Universitetssjukhuset /ID# 255236 — Gothenburg

United Kingdom · 3 centers

Center list to be confirmed — check the primary protocol.

Czechia · 2 centers

• Vseobecna Fakultni nemocnice v Praze /ID# 256096 — Prague
• Fakultni nemocnice Motol a Homolka /ID# 256547 — Prague

Germany · 2 centers

• Dr. von Haunerschen Kinderspital /ID# 255577 — Munich
• Universitaetsklinikum Muenster /ID# 256762 — Münster

Israel · 2 centers

• Schneider Children's Medical Center /ID# 254950 — Petah Tikva
• Shaare Zedek Medical Center /ID# 254951 — Jerusalem

Poland · 2 centers

• Gastromed Sp. z o.o /ID# 255939 — Torun
• Instytut Pomnik - Centrum Zdrowia Dziecka /ID# 255938 — Warsaw

Puerto Rico · 2 centers

• Puerto Rico Health Institute /ID# 255071 — Dorado
• Clinical Research Puerto Rico /ID# 266479 — San Juan

Switzerland · 2 centers

• University Children's Hospital Zurich - Eleonorenstiftung /ID# 255337 — Zurich
• Inselspital, Universitaetsspital Bern /ID# 255321 — Bern

Taiwan · 2 centers

• Changhua Christian Hospital /ID# 256082 — Changhua City, Changhua County
• National Taiwan University Hospital /ID# 255679 — Taipei

Netherlands · 1 center

• Amsterdam UMC, locatie AMC /ID# 254827 — Amsterdam

Identifiers

NCT: NCT05995353 · M16-194 · 2022-502050-14-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗