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
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 110
- 试验地点
- 147
- 主要终点
- Cohort 3 (Substudy 2): Percentage of Participants Achieving Pediatric Crohn's Disease Activity Index (PCDAI) Clinical Remission
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 2 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
PK Cohort 2: SS2 Dose A
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.
干预措施: Risankizumab (Drug)
PK Cohort 2: SS3 Dose A
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.
干预措施: Risankizumab (Drug)
PK Cohort 1: SS1
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.
干预措施: Risankizumab (Drug)
Expansion Cohort 3: SS1
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.
干预措施: Risankizumab (Drug)
PK Cohort 2: SS3 Dose B
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.
干预措施: Risankizumab (Drug)
PK Cohort 2: SS2 Dose B
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.
干预措施: Risankizumab (Drug)
PK Cohort 1: SS2 Dose A
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.
干预措施: Risankizumab (Drug)
PK Cohort 1: SS3 Dose B
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.
干预措施: Risankizumab (Drug)
PK Cohort 1: SS3 Dose A
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.
干预措施: Risankizumab (Drug)
PK Cohort 1: SS2 Dose B
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.
干预措施: Risankizumab (Drug)
PK Cohort 2: SS1
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.
干预措施: Risankizumab (Drug)
Expansion Cohort 3: SS3 Dose A
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.
干预措施: Risankizumab (Drug)
Expansion Cohort 3: SS3 Dose B
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.
干预措施: Risankizumab (Drug)
Expansion Cohort 3: SS2 Dose B
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.
干预措施: Risankizumab (Drug)
Expansion Cohort 3: SS2 Dose A
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.
干预措施: Risankizumab (Drug)
结局指标
主要结局
Cohort 3 (Substudy 2): Percentage of Participants Achieving Pediatric Crohn's Disease Activity Index (PCDAI) Clinical Remission
时间窗: 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
时间窗: 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
时间窗: 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)
时间窗: 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
时间窗: Up to approximately Week 64
Cmax of risankizumab
次要结局
- Cohort 3 (Substudy 1): Percentage of Participants Achieving Endoscopic Response per SES-CD(At 12 weeks)
- Cohort 3 (Substudy 1): Percentage of Participants Achieving Endoscopic Remission per SES-CD(At 12 weeks)
- Cohorts 1 & 2 (Substudy 2): Percentage of Participants Achieving Corticosteroid-Free Clinical Remission per PCDAI(At 64 weeks)
- Cohort 3 (Substudy 1): Percentage of Participants Achieving PCDAI Clinical Remission(At 12 weeks)
- Cohorts 1 & 2 (Substudy 1): Percentage of Participants Achieving PCDAI Clinical Remission(At 12 weeks)
- Cohorts 1 & 2 (Substudy 2): Percentage of Participants Achieving Endoscopic Remission per SES-CD(At 64 weeks)
- Cohort 3 (Substudy 2): Percentage of Participants Achieving Endoscopic Remission per SES-CD(At 64 weeks)
- Cohorts 1 & 2 (Substudy 2): Percentage of Participants Achieving PCDAI Clinical Remission(At 64 weeks)
- Cohorts 1 & 2 (Substudy 1): Percentage of Participants Achieving Endoscopic Response per SES-CD(At 12 weeks)
- Cohort 3 (Substudy 2): Percentage of Participants Achieving Corticosteroid-Free Clinical Remission per PCDAI(At 64 weeks)
- Cohorts 1 & 2 (Substudy 2): Percentage of Participants Achieving Endoscopic Response per SES-CD(At 64 weeks)
- Cohorts 1 & 2 (Substudy 1): Percentage of Participants Achieving Endoscopic Remission per SES-CD(At 12 weeks)