An Open-Label, Phase 3 Study to Evaluate the Pharmacokinetics, Safety, and Immunogenicity of Vedolizumab Subcutaneous in Pediatric Subjects With Moderately to Severely Active Ulcerative Colitis or Crohn's Disease Who Achieved Clinical Response Following Open-Label Vedolizumab Intravenous Therapy
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 70
- 试验地点
- 100
- 主要终点
- Ctrough,ss: Steady-state Median Observed Plasma Concentration at the End of a Dosing Interval for Vedolizumab at Week 34
研究概览
简要总结
The main aim of this study is to learn how the body of a child or teenager with moderately to severely active ulcerative colitis (UC) or Crohn's disease (CD) processes vedolizumab (pharmacokinetics) given just under the skin subcutaneously (SC).
The participants will be treated with vedolizumab for up to 34 weeks.
During the study, participants will visit their study clinic several times.
详细描述
The drug being tested in this study is vedolizumab. Vedolizumab is being tested to treat pediatric participants with moderate to severe active UC or CD who achieved clinical response following open-label vedolizumab intravenous (IV) therapy. The study will look at the pharmacokinetics, safety, and immunogenicity of vedolizumab.
The study will enroll approximately 70 patients. During the Induction Period participants will receive 3 doses of vedolizumab IV infusion at Day 1, Week 2, and Week 6 based on their weight at Baseline as:
- Participants ≥30 kilograms (kg), Vedolizumab (High Dose)
- Participants >15 to <30 kg, Vedolizumab (Medium Dose)
- Participants ≥10 to ≤15 kg, Vedolizumab (Low Dose)
At Week 14, participants who achieve clinical response will be assigned to one of the following groups, stratified by weight to receive vedolizumab 108 mg SC injection during the 20-week Maintenance Period:
- Participants ≥30 kg, Vedolizumab 108 mg once every 2 weeks (Q2W)
- Participants ≥10 to <30 kg, Vedolizumab 108 mg once every 4 weeks (Q4W)
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
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
- •The participant weighs ≥10 kg at the time of screening and enrollment into the study.
- •Participants with UC or CD diagnosed at least 1 month before screening. Participants with moderately to severely active disease defined as:
- •Participants with UC: a modified Mayo score of 5 to 9 (sum of Mayo endoscopic subscore, stool frequency subscore, and rectal bleeding subscore) with a Mayo endoscopic subscore of ≥2 (with the presence of mucosal friability excluding an endoscopic subscore of 1 and mandating a score of at least 2). (The results of screening endoscopy should be applied.)
- •Participants with CD: a pediatric Crohn's disease activity index (PCDAI) >30 and a simple endoscopic score for Crohn's disease (SES-CD) >6 (or an SES-CD ≥4 if disease is confined to terminal ileum) at screening endoscopy.
- •Participants who have failed, lost response to, or been intolerant to treatment with at least 1 of the following agents: corticosteroids, immunomodulators (for example, azathioprine [AZA], 6-mercaptopurine [6-MP], methotrexate [MTX]), and/or tumor necrosis factor (TNF)-α antagonist therapy (for example, infliximab, adalimumab).
- •Participants with evidence of UC extending proximal to the rectum (that is, not limited to proctitis), at a minimum.
- •Participants with extensive colitis or pancolitis of >8 years' duration or left-sided colitis of >12 years' duration must have documented evidence of a negative surveillance colonoscopy within 12 months before screening.
- •Participants with vaccinations that are up-to-date based on the countrywide accepted schedule of childhood vaccines.
排除标准
- •Participants who have had previous exposure to approved or investigational anti-integrins, including but not limited to, natalizumab, efalizumab, etrolizumab, or abrilumab (AMG 181); or mucosal addressin cell adhesion molecule-1 (MAdCAM-1) antagonists (ontamalimab), or rituximab.
- •Participants who have had prior exposure to vedolizumab.
- •Participants with hypersensitivity or allergies to vedolizumab or any of its excipients.
- •Participants with active cerebral/meningeal disease, signs/symptoms or history of progressive multifocal leukoencephalopathy (PML) or any other major neurological disorders.
- •The participant has received any live vaccinations within 30 days before first dose of study drug.
- •Participants who currently require surgical intervention or are anticipated to require surgical intervention for UC or CD during this study.
- •Participants who have had subtotal or total colectomy or have a jejunostomy, ileostomy, colostomy, ileo-anal pouch, known fixed stenosis of the intestine, short bowel syndrome, or >3 small intestine resections.
- •Participants with a current diagnosis of indeterminate colitis.
- •Participants with clinical features suggesting monogenic very early-onset inflammatory bowel disease (IBD).
- •Participants with active or latent tuberculosis (TB).
- •Participants with evidence of positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb). Hepatitis B virus (HBV) immune subjects (that is, HBsAg negative and hepatitis B surface antibody [anti-HBs]-positive) may, however, be included.
- •The participant has any identified congenital or acquired immunodeficiency (for example, common variable immunodeficiency, human immunodeficiency virus [HIV] infection, organ transplantation).
- •Participants with positive stool studies for ova and/or parasites or stool culture at screening visit.
- •Participants with positive Clostridioides difficile (C difficile) stool test at screening visit.
研究组 & 干预措施
Induction Period: Participants >15 to <30 kg, Vedolizumab (Medium Dose) IV
Participants weighing >15 to <30 kg will receive vedolizumab (Medium Dose), IV infusion, at Day 1, Weeks 2 and 6 in the Induction Period.
干预措施: Vedolizumab IV (Drug)
Induction Period: Participants ≥30 kg, Vedolizumab (High Dose) IV
Participants weighing ≥30 kg will receive vedolizumab (High Dose) IV infusion, at Day 1, Weeks 2 and 6 in the Induction Period.
干预措施: Vedolizumab IV (Drug)
Maintenance Period: Participants ≥10 to <30 kg, Vedolizumab 108 mg SC Q4W
Participants with clinical response at Week 14 weighing ≥10 to <30 kg will receive vedolizumab 108 mg, SC injection, Q4W from Week 14 to Week 30 in the Maintenance Period.
干预措施: Vedolizumab SC (Drug)
Induction Period: Participants ≥10 to ≤15 kg, Vedolizumab (Low Dose) IV
Participants weighing ≥10 to ≤15 kg will receive vedolizumab (Low Dose), IV infusion, at Day 1, Weeks 2 and 6 in the Induction Period.
干预措施: Vedolizumab IV (Drug)
Maintenance Period: Participants ≥30 kg, Vedolizumab 108 mg SC Q2W
Participants with clinical response at Week 14 weighing ≥30 kg will receive vedolizumab 108 mg, SC injection, Q2W from Week 14 to Week 32 in the Maintenance Period.
干预措施: Vedolizumab SC (Drug)
结局指标
主要结局
Ctrough,ss: Steady-state Median Observed Plasma Concentration at the End of a Dosing Interval for Vedolizumab at Week 34
时间窗: Predose at Week 34
Cavg,ss: Average Serum Concentration at Steady-state for Vedolizumab at Week 34
时间窗: Multiple time points prior to Week 34; pre-dose at Week 34
次要结局
- Percentage of Participants with Positive Antivedolizumab Antibody (AVA)(Baseline up to 18 weeks after last dose of study drug (up to Week 50))
- Percentage of Participants with Positive Neutralizing AVA(Baseline up to 18 weeks after last dose of study drug (up to Week 50))