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
- Registration Number
- NCT05995353
- Lead Sponsor
- AbbVie
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 110
- 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
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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
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Any of the following medical disorders:
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Current diagnosis of ulcerative colitis, indeterminate colitis, or monogenic IBD.
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A diagnosis of CD prior to 2 years of age.
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A diagnosis or suspected diagnosis of a primary immunodeficiency.
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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.
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Ostomy or ileoanal pouch.
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Diagnosis of short gut or short bowel syndrome.
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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.
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Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Expansion Cohort 3: SS3 Dose B Risankizumab 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. Expansion Cohort 3: SS3 Dose A Risankizumab 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. Expansion Cohort 3: SS2 Dose B Risankizumab 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. PK Cohort 2: SS3 Dose A Risankizumab 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. PK Cohort 1: SS1 Risankizumab 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. PK Cohort 1: SS2 Dose B Risankizumab 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. PK Cohort 1: SS2 Dose A Risankizumab 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. PK Cohort 1: SS3 Dose A Risankizumab 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. PK Cohort 2: SS1 Risankizumab 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. PK Cohort 1: SS3 Dose B Risankizumab 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. PK Cohort 2: SS2 Dose B Risankizumab 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. PK Cohort 2: SS2 Dose A Risankizumab 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. Expansion Cohort 3: SS1 Risankizumab 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. PK Cohort 2: SS3 Dose B Risankizumab 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. Expansion Cohort 3: SS2 Dose A Risankizumab 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.
- Primary Outcome Measures
Name Time Method Cohort 3 (Substudy 2): Percentage of Participants Achieving Pediatric Crohn's Disease Activity Index (PCDAI) Clinical Remission At 64 weeks 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.
Cohorts 1 & 2: Time to Cmax (Tmax) of Risankizumab Up to approximately 64 weeks Tmax of risankizumab
Cohorts 1 & 2: Area Under the Serum Concentration-Time Curve Over the Dosing Interval (AUCtau) of Risankizumab Up to approximately 64 weeks AUCtau of risankizumab
Cohort 3 (Substudy 2): Percentage of Participants Achieving Endoscopic Response per Simple Endoscopic Score for Crohn's Disease (SES-CD) At 64 weeks 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).
Cohorts 1 & 2: Maximum Observed Serum Concentration (Cmax) of Risankizumab Up to approximately Week 64 Cmax of risankizumab
- Secondary Outcome Measures
Name Time Method Cohort 3 (Substudy 1): Percentage of Participants Achieving Endoscopic Response per SES-CD At 12 weeks 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).
Cohort 3 (Substudy 1): Percentage of Participants Achieving Endoscopic Remission per SES-CD At 12 weeks 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.
Cohorts 1 & 2 (Substudy 2): Percentage of Participants Achieving Corticosteroid-Free Clinical Remission per PCDAI At 64 weeks 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.
Cohort 3 (Substudy 1): Percentage of Participants Achieving PCDAI Clinical Remission At 12 weeks 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.
Cohorts 1 & 2 (Substudy 1): Percentage of Participants Achieving PCDAI Clinical Remission At 12 weeks 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.
Cohorts 1 & 2 (Substudy 2): Percentage of Participants Achieving Endoscopic Remission per SES-CD At 64 weeks 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.
Cohort 3 (Substudy 2): Percentage of Participants Achieving Endoscopic Remission per SES-CD At 64 weeks 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.
Cohorts 1 & 2 (Substudy 2): Percentage of Participants Achieving PCDAI Clinical Remission At 64 weeks 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.
Cohorts 1 & 2 (Substudy 1): Percentage of Participants Achieving Endoscopic Response per SES-CD At 12 weeks 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).
Cohort 3 (Substudy 2): Percentage of Participants Achieving Corticosteroid-Free Clinical Remission per PCDAI At 64 weeks 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.
Cohorts 1 & 2 (Substudy 2): Percentage of Participants Achieving Endoscopic Response per SES-CD At 64 weeks 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).
Cohorts 1 & 2 (Substudy 1): Percentage of Participants Achieving Endoscopic Remission per SES-CD At 12 weeks 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.
Trial Locations
- Locations (61)
Peking University Third Hospital /ID# 255876
🇨🇳Beijing, Beijing, China
Phoenix Children's Hospital /ID# 255766
🇺🇸Phoenix, Arizona, United States
Arkansas Children's Hospital /ID# 255762
🇺🇸Little Rock, Arkansas, United States
UCSF Benioff Children's Hospital - Oakland /ID# 258327
🇺🇸Oakland, California, United States
Children's Hospital Colorado - Aurora /ID# 255764
🇺🇸Aurora, Colorado, United States
Arnold Palmer Hospital for Children Center Digestive Health & Nutrition - Orland /ID# 255437
🇺🇸Orlando, Florida, United States
Indiana University Health Riley Hospital for Children /ID# 256454
🇺🇸Indianapolis, Indiana, United States
Massachusetts General Hospital /ID# 255767
🇺🇸Boston, Massachusetts, United States
MNGI Digestive Health, P. A. /ID# 255366
🇺🇸Minneapolis, Minnesota, United States
Goryeb Children's Hospital /ID# 256452
🇺🇸Morristown, New Jersey, United States
Icahn School of Medicine at Mount Sinai /ID# 254880
🇺🇸New York, New York, United States
Uza /Id# 255114
🇧🇪Edegem, Antwerpen, Belgium
Cliniques Universitaires UCL Saint-Luc /ID# 255108
🇧🇪Woluwe-Saint-Lambert, Bruxelles-Capitale, Belgium
Universitair Ziekenhuis Leuven /ID# 255098
🇧🇪Leuven, Vlaams-Brabant, Belgium
Hospital Universite Enfants Reine Fabiola /ID# 255112
🇧🇪Bruxelles, Belgium
UMHAT Sveti Georgi /ID# 255386
🇧🇬Plovdiv, Bulgaria
Specialized Hospital For Active Treatment Of Children Diseases Prof. Ivan Mitev /ID# 255384
🇧🇬Sofiya, Bulgaria
London Health Sciences Center- University Hospital /ID# 258598
🇨🇦London, Ontario, Canada
Universitair Ziekenhuis Brussel /ID# 255109
🇧🇪Jette, Bruxelles-Capitale, Belgium
Groupe Sante CHC - Clinique du MontLegia /ID# 255620
🇧🇪Liege, Belgium
UMHAT Sveta Marina /ID# 256358
🇧🇬Varna, Bulgaria
Alberta Children's Hospital /ID# 255357
🇨🇦Calgary, Alberta, Canada
Beijing Children's Hospital /ID# 256081
🇨🇳Beijing, Beijing, China
Ruijin Hospital, Shanghai Jiaotong University School of Medicine /ID# 255688
🇨🇳Shanghai, Shanghai, China
Fakultní nemocnice v Motole /ID# 256547
🇨🇿Prague, Praha 5, Czechia
Vseobecna fakultni nemocnice v Praze /ID# 256096
🇨🇿Praha, Czechia
CHRU Tours - Hopital Gatien de Clocheville /ID# 255052
🇫🇷Tours, Centre-Val De Loire, France
CHU Bordeaux - Hopital Pellegrin /ID# 257060
🇫🇷Bordeaux, Nouvelle-Aquitaine, France
HCL - Hopital Femme Mere Enfant /ID# 255443
🇫🇷Bron CEDEX, Rhone, France
AP-HP - Hopital Necker /ID# 255608
🇫🇷Paris, France
CHU Toulouse - Hopital Paule de Viguier /ID# 255609
🇫🇷Toulouse, France
Dr. von Haunerschen Kinderspital /ID# 255577
🇩🇪Muenchen, Bayern, Germany
Universitaetsklinikum Muenster /ID# 256762
🇩🇪Muenster, Nordrhein-Westfalen, Germany
Schneider Children's Medical Center /ID# 254950
🇮🇱Petah Tikva, HaMerkaz, Israel
Shaare Zedek Medical Center /ID# 254951
🇮🇱Jerusalem, Yerushalayim, Israel
IRCCS Istituto Giannina Gaslini /ID# 255262
🇮🇹Genoa, Genova, Italy
Azienda Ospedaliera Universitaria Federico II /ID# 255045
🇮🇹Naples, Napoli, Italy
Azienda Ospedaliera Universitaria Gaetano Martino /ID# 255044
🇮🇹Messina, Italy
Seoul National University Hospital /ID# 255318
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
Yonsei University Health System Severance Hospital /ID# 256976
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
Samsung Medical Center /ID# 255284
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
Kyungpook National University Chilgok Hospital /ID# 255817
🇰🇷Daegu, Korea, Republic of
Amsterdam UMC, locatie AMC /ID# 254827
🇳🇱Amsterdam, Noord-Holland, Netherlands
Gastromed Sp. z o.o /ID# 255939
🇵🇱Torun, Kujawsko-pomorskie, Poland
Instytut Pomnik - Centrum Zdrowia Dziecka /ID# 255938
🇵🇱Warszawa, Mazowieckie, Poland
Puerto Rico Health Institute /ID# 255071
🇵🇷Dorado, Puerto Rico
Clinical Research Puerto Rico /ID# 266479
🇵🇷San Juan, Puerto Rico
Hospital Arquitecto Marcide - Complejo Hospitalario Universitario de Ferrol /ID# 255614
🇪🇸Ferrol, A Coruna, Spain
Hospital Infantil Universitario Nino Jesus /ID# 255012
🇪🇸Madrid, Spain
Hospital Regional Universitario de Malaga /ID# 257553
🇪🇸Malaga, Spain
Karolinska University Hospital Solna /ID# 255240
🇸🇪Solna, Stockholms Lan, Sweden
Sodersjukhuset /ID# 255239
🇸🇪Stockholm, Stockholms Lan, Sweden
Sahlgrenska Universitetssjukhuset /ID# 255236
🇸🇪Göteborg, Vastra Gotalands Lan, Sweden
Kinderspital Zurich - Eleonorenstiftung /ID# 255337
🇨🇭Zurich, Zuerich, Switzerland
Inselspital, Universitaetsspital Bern /ID# 255321
🇨🇭Bern, Switzerland
National Taiwan University Hospital /ID# 255679
🇨🇳Taipei City, Taipei, Taiwan
Changhua Christian Hospital /ID# 256082
🇨🇳Changhua City, Changhua County, Taiwan
Gazi University Medical Faculty /ID# 255086
🇹🇷Ankara, Turkey
Kocaeli University Med Faculty /ID# 256922
🇹🇷Kocaeli, Turkey
Sheffield Children's Hospital NHS Foundation Trust /ID# 255758
🇬🇧Sheffield, England, United Kingdom
Barts Health NHS Trust /ID# 255757
🇬🇧London, Greater London, United Kingdom