A Phase 4, Multicenter, Open-label Study of Serum Infliximab Concentrations and Efficacy and Safety of Dose Escalation in Pediatric Patients With Inflammatory Bowel Disease
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 入组人数
- 53
- 主要终点
- Clinical Response at Week 16 After Dose Escalation as Evaluated by Pediatric Crohn's Disease Activity Index (PCDAI) in Crohn's Disease (CD) Participants
研究概览
简要总结
The purpose of this study is to evaluate whether trough serum infliximab concentrations at the time of loss of clinical response will identify pediatric participants with inflammatory bowel disease (IBD) who would benefit (regain clinical response) from dose escalation above the currently approved dose [5 milligram (mg)/kilogram (kg) every 8 weeks (q8wk)] and the safety of that dose escalation.
详细描述
This is a multicenter (when more than one hospital or medical school team work on a medical research study), prospective (study following participants forward in time), open-label (all people know the identity of the intervention) study of infliximab in pediatric participants with inflammatory bowel disease. The study consists of 3 Phases: screening Phase (up to 4 weeks), open-label treatment Phase (56 weeks) and follow up safety Phase (8 weeks). The duration of participation in the study for each participant is approximately up to 68 weeks (including screening period). Participants' efficacy and safety outcomes will be monitored throughout the study.
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
- 6 Years 至 16 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Must have a biopsy-confirmed diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) prior to study entry
- •Must meet concomitant medication stability criteria as specified in protocol
- •Is considered eligible according to the tuberculosis (TB) Screening criteria specified in protocol
- •Must have negative stool results for enteric pathogens. Stool studies must include a stool culture and Clostridium difficile toxin assay. These must have been performed during Screening or the current episode of disease exacerbation as long as the stool studies were performed within 4 months prior to the first administration of infliximab at Week 0
- •Must have screening laboratory test results as specfied in the protocol
- •Must be up to date with all immunizations in agreement with current local immunization guidelines for immunosuppressed participants prior to Screening
- •Must not have discontinued infliximab therapy
排除标准
- •Must not require, or must not have required, within the 2 months prior to Screening, surgery for active gastrointestinal bleeding, peritonitis, intestinal obstruction, or intraabdominal or pancreatic abscess requiring surgical drainage, or other conditions possibly confounding the evaluation of benefit from infliximab treatment
- •Must not have presence or history of colonic or small bowel obstruction within 6 months prior to Screening, confirmed by objective radiographic or endoscopic evidence of a stricture with resulting obstruction (example, dilation of the colon or small bowel proximal to the stricture on barium radiograph or an inability to traverse the stricture at endoscopy)
- •Must not have local manifestations of CD, such as fistulae, strictures, abscesses, or other disease complications for which surgery might be indicated. Enterocutaneuous fistulae for which surgery is not indicated, are allowed
- •Must not have presence of a stoma
- •Must not have documented short bowel syndrome (more than 100 centimeter in total of small bowel resected)
研究组 & 干预措施
Dose Escalation Group
Participants must have completed: a) recommended infliximab induction dosing regimen of 5 milligram (mg)/kilogram (kg) at Weeks 0, 2, and 6, followed by at least 1 maintenance doses of 5 mg/kg every 8 weeks (q8wk); or b) induction regimen with doses >6 mg/kg and have received at least 2 maintenance doses of 5 mg/kg q8wk with clinical response for at least 28 days after the most recent 5 mg/kg maintenance dose; or c) maintenance doses >6 mg/kg within past 6 months and at least 2 maintenance doses of 5 mg/kg q8wk with clinical response for at least 28 days after the most recent 5 mg/kg maintenance dose; d) must have lost clinical response, after first or subsequent q8wk maintenance dose of infliximab 5 mg/kg for participants who have completed the recommended infliximab induction dosing regimen or, after most recent (second or later) q8wk maintenance dose of infliximab 5 mg/kg for participants with an induction regimen with doses >6 mg/kg or with previous maintenance doses >6 mg/kg.
干预措施: Infliximab (Drug)
Reference Group
Participants must have completed: a) the recommended infliximab induction dosing regimen of 5 mg/kg at Weeks 0, 2, and 6, and have maintained a stable clinical response to infliximab after at least 1 maintenance doses of 5 mg/kg q8wk; or b) an induction regimen with doses >6 mg/kg and have received at least 2 maintenance doses of 5 mg/kg q8wk and have maintained clinical response for at least 28 days after the most recent 5 mg/kg maintenance dose 5 mg/kg maintenance dose; or c) maintenance doses >6 mg/kg within the past 6 months and at least 2 maintenance doses of 5 mg/kg q8wk and have maintained a clinical response for at least 28 days after the most recent 5 mg/kg maintenance dose 5 mg/kg maintenance dose.
干预措施: Infliximab (Drug)
结局指标
主要结局
Clinical Response at Week 16 After Dose Escalation as Evaluated by Pediatric Crohn's Disease Activity Index (PCDAI) in Crohn's Disease (CD) Participants
时间窗: Week 16
Clinical response was defined as Crohn's disease (CD) participants with decrease from baseline in PCDAI of greater than or equal to (\>=) 15 points with total score of less than or equal to (\<=) 30 points. PCDAI includes three history items (abdominal pain, number of liquid stools, general wellbeing), five physical examination items (abdominal examination, perirectal disease, extraintestinal manifestations, weight, height), and three laboratory tests (hematocrit, albumin, erythrocyte sedimentation rate). Items are scored on a three-point scale (zero, 5, or 10 points) except for hematocrit and erythrocyte sedimentation rate which are scored as zero, 2.5 or 5 points. PCDAI scores can range from zero to 125 with higher scores indicating more active disease. Data for this OM was planned to be analyzed for Dose escalation (DE) group only.
Clinical Response at Week 16 After Dose Escalation as Evaluated by Mayo Score in Ulcerative Colitis (UC) Participants
时间窗: Week 16
Clinical Response as per Mayo score was defined as decrease from baseline in partial Mayo score of \>= 2 points and \>= 30 percent (%) and decrease in rectal bleeding sub-score by \>= 1 point or achievement of an absolute sub-score of less than or equal to (\<=) 1 point (for UC participants). A Partial Mayo Score which is Mayo score without endoscopy ranges from 0 (normal or inactive disease) to 9 (severe disease) and calculated as the sum of 3 subscores (stool frequency, rectal bleeding and physician's global assessment \[PGA\]) with each ranging from 0 to 3 (0=normal, 1=mild, 2=moderate, 3=severe). Data for this OM was planned to be analyzed for the DE group only.
次要结局
- Sustained Clinical Response Through 56 Weeks After Dose Escalation(Up to Week 56)
- Change From Baseline in Abdominal Pain and Loose/Watery Stool Frequency Sub-scores of the PCDAI at Week 16 and Week 56 in CD Participants(Baseline, Week 16 and Week 56)
- Change From Baseline in Abdominal Pain Using the Wong-Baker FACES Scale at Week 16 and Week 56 in CD Participants(Baseline, Week 16 and Week 56)
- Change From Baseline in Absolute Stool Frequency Based on PCDAI Score at Week 16 and Week 56 in CD Participants(Baseline, Week 16 and Week 56)
- Change From Baseline in Stool Frequency Sub-Score of the Partial Mayo Score at Week 16 and Week 56 in UC Participants(Baseline, Week 16 and Week 56)
- Change From Baseline in Rectal Bleeding Sub-Scores of the Partial Mayo Score at Week 16 and Week 56 in UC Participants(Baseline, Week 16 and Week 56)
- Change From Baseline in Abdominal Pain Using the Wong-Baker FACES Scale at Week 16 and Week 56 in UC Participants(Baseline, Week 16 And Week 56)
- Change From Baseline in Absolute Stool Frequency at Week 16 and Week 56 in UC Participants(Baseline, Week 16 And Week 56)
- Correlation of Wong-Baker FACES Scale With Clinical Remission and Response at Week 16(Week 16)
- Relationship Between Abdominal Pain PCDAI Sub-Score And the Wong-Baker Faces Scale For CD Participants(Week 16 and 56)