A Study to Learn More About How Risankizumab Works in Young Participants With Ulcerative Colitis
- Registration Number
- NCT07071519
- Lead Sponsor
- AbbVie
- Brief Summary
Ulcerative colitis (UC) is a type of inflammatory bowel disease that causes inflammation and bleeding from the lining of the rectum and colon (large intestine). This study will assess how Risankizumab moves through the body as well as how safe and effective it is in treating pediatric participants with moderate to severely active UC. Adverse events and change in disease activity will be assessed.
Risankizumab is an approved medication for moderate to severe UC in multiple countries and is being developed for the treatment of UC 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 maintenance regimen of risankizumab. SS3 is an open-label extension period where participants will receive risankizumab based off of their response in SS2. Around 120 pediatric participants with UC will be enrolled at around 80 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
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 120
- Active ulcerative colitis (UC) with an modified Mayo Score (mMS) of 5 to 9 points and endoscopic subscore of 2 to 3 (confirmed by central reader).
- Demonstrated intolerance or inadequate response (IR) to one or more of the following categories of drugs:
aminosalicylates (except in countries where failure of this drug class is not sufficient for eligibility), oral locally acting corticosteroids, systemic steroids (prednisone or equivalent), immunomodulators (IMMs), and/or biologic therapies, as outlined in the protocol.
- Subjects must have a documented history of UC for at least 3 months prior to Baseline, confirmed by colonoscopy during the screening period, with exclusion of current infection, colonic dysplasia and/or malignancy. Documentation of pathology results consistent with the diagnosis of UC must be available.
- Participants who have had a major surgery performed within 12 weeks prior to Baseline or planned during the conduct of the study (e.g., inguinal hernia repair, cholecystectomy, intestinal resection).
- Participants who have concurrent clinically significant medical conditions other than the indication being studied or any other reason that the investigator determines would interfere with the subject's participation in this study, would make the subject an unsuitable candidate to receive study treatment, or would put the subject at risk by participating in the study.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description 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 participants who complete SS1 are eligible to enter SS2 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: 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: 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 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: 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 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. 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: 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 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: 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 participants who complete SS1 are eligible to enter 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 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: 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 double-blind risankizumab Dose B. Participants who complete SS2 will have the opportunity to enter the open-label long term extension SS3. 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: 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.
- Primary Outcome Measures
Name Time Method PK Lead-In Cohort 1: Maximum Observed Serum Concentration (Cmax) At Week 64 Maximum observed plasma concentration (Cmax)
PK Lead-In Cohort 2: Maximum Observed Serum Concentration (Cmax) At Week 64 Maximum observed plasma concentration (Cmax)
PK Lead-In Cohort 1: Time to Maximum Serum Concentration (Tmax) At Week 64 Time to maximum plasma concentration (Tmax)
PK Lead-In Cohort 2: Time to Maximum Serum Concentration (Tmax) At Week 64 Time to maximum plasma concentration (Tmax)
PK Lead-In Cohort 1: Area Under the Serum Concentration-Time Curve Over the Dosing Interval (AUCtau) At Week 64 Area under the serum concentration-time curve over the dosing interval (AUCtau)
PK Lead-In Cohort 2: Area Under the Serum Concentration-Time Curve Over the Dosing Interval (AUCtau) At Week 64 Area under the serum concentration-time curve over the dosing interval (AUCtau)
Expansion Cohort 3: Achievement of Clinical Remission per Modified Mayo Score (mMS) Among Week 12 Clinical Responders per mMS At Week 64 Clinical remission on the mMS is defined as defined as Stool Frequency Subscore (SFS) ≤ 1 and not greater than Baseline, Rectal Bleeding Subscore (RBS) = 0, and Mayo Endoscopic Subscore (MES) ≤ 1
Number of Participants With Adverse Events Up to 292 Weeks An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The investigator assessed the relationship of each event to the use of study drug as either probably related, possibly related, probably not related or not related
- Secondary Outcome Measures
Name Time Method PK Lead-In Cohort 1: Achievement of clinical remission per mMS among Week 12 responders per mMS At Week 64 Clinical remission on the mMS is defined as defined as Stool Frequency Subscore (SFS) ≤ 1 and not greater than Baseline, Rectal Bleeding Subscore (RBS) = 0, and Mayo Endoscopic Subscore (MES) ≤ 1
PK Lead-In Cohort 2: Achievement of clinical remission per mMS among Week 12 responders per mMS At Week 64 Clinical remission on the mMS is defined as defined as Stool Frequency Subscore (SFS) ≤ 1 and not greater than Baseline, Rectal Bleeding Subscore (RBS) = 0, and Mayo Endoscopic Subscore (MES) ≤ 1
PK Lead-In Cohort 1: Achievement of clinical remission per mMS At Week 12 Clinical remission on the mMS is defined as Stool Frequency Subscore (SFS) ≤ 1 and not greater than Baseline, Rectal Bleeding Subscore (RBS) = 0, and Mayo Endoscopic Subscore (MES) ≤ 1
PK Lead-In Cohort 2: Achievement of clinical remission per mMS At Week 12 Clinical remission on the mMS is defined as Stool Frequency Subscore (SFS) ≤ 1 and not greater than Baseline, Rectal Bleeding Subscore (RBS) = 0, and Mayo Endoscopic Subscore (MES) ≤ 1
PK Lead-In Cohort 1: Achievement of clinical response per mMS At Week 12 Clinical response per mMS is defined as decrease in mMS by ≥ 2 points and ≥ 30% from Baseline with a decrease in Rectal Bleeding Subscore (RBS) of ≥ 1 or an absolute RBS of 0 or 1.
PK Lead-In Cohort 2: Achievement of clinical response per mMS At Week 12 Clinical response per mMS is defined as decrease in mMS by ≥ 2 points and ≥ 30% from Baseline with a decrease in Rectal Bleeding Subscore (RBS) of ≥ 1 or an absolute RBS of 0 or 1.
PK Lead-In Cohort 1: Achievement of endoscopic improvement At Week 12 Endoscopic improvement defined as MES ≤ 1
PK Lead-In Cohort 2: Achievement of endoscopic improvement At Week 12 Endoscopic improvement defined as MES ≤ 1
PK Lead-In Cohort 1: Symptomatic response per partial mMS At Week 12 Symptomatic response per partial mMS is defined as decrease in partial mMS by ≥ 1 points and ≥ 30% from Baseline with decrease in RBS of ≥ 1 or an absolute RBS of 0 or 1.
PK Lead-In Cohort 2: Symptomatic response per partial mMS At Week 12 Symptomatic response per partial mMS is defined as decrease in partial mMS by ≥ 1 points and ≥ 30% from Baseline with decrease in RBS of ≥ 1 or an absolute RBS of 0 or 1.
PK Lead-In Cohort 1: Achievement of clinical response per mMS among Week 12 responders per mMS At Week 64 Clinical response per mMS is defined as decrease in mMS by ≥ 2 points and ≥ 30% from Baseline with a decrease in Rectal Bleeding Subscore (RBS) of ≥ 1 or an absolute RBS of 0 or 1.
PK Lead-In Cohort 2: Achievement of clinical response per mMS among Week 12 responders per mMS At Week 64 Clinical response per mMS is defined as decrease in mMS by ≥ 2 points and ≥ 30% from Baseline with a decrease in Rectal Bleeding Subscore (RBS) of ≥ 1 or an absolute RBS of 0 or 1.
PK Lead-In Cohort 1: Achievement of endoscopic improvement among Week 12 responders per mMS At Week 64 Endoscopic improvement defined as MES ≤ 1
PK Lead-In Cohort 2: Achievement of endoscopic improvement among Week 12 responders per mMS At Week 64 Endoscopic improvement defined as MES ≤ 1
PK Lead-In Cohort 1: Ability to discontinue corticosteroids prior to Week 64 (at least 90 days without corticosteroid exposure) and achievement of clinical remission per mMS among Week 12 responders per mMS Up to Week 64 PK Lead-In Cohort 2: Ability to discontinue corticosteroids prior to Week 64 (at least 90 days without corticosteroid exposure) and achievement of clinical remission per mMS among Week 12 responders per mMS Up to Week 64 Expansion Cohort 3: Achievement of clinical remission per mMS At Week 12 Expansion Cohort 3: Achievement of clinical response per mMS At Week 12 Expansion Cohort 3: Achievement of endoscopic improvement At Week 12 Expansion Cohort 3: Symptomatic response per partial mMS At Week 12 Expansion Cohort 3: Achievement of clinical response per mMS among Week 12 responders per mMS At Week 64 Expansion Cohort 3: Achievement of endoscopic improvement among Week 12 responders per mMS At Week 64 Expansion Cohort 3: Achievement of corticosteroid-free clinical remission per mMS among Week 12 responders per mMS At Week 64