Model-informed Infliximab Dose De-escalation Following Earlier Dose Escalation in Adult Patients With Inflammatory Bowel Diseases
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Steroid-free, combined clinical and biological remission
研究概览
简要总结
This is a monocentric, two-arm, non-randomised, non-blinded, historically controlled, interventional trial. The purpose of this trial is to investigate the effect of model-informed infliximab dose de-escalation on the infliximab exposure and therapeutic outcome as compared to standard dose de-escalation in patients with inflammatory bowel diseases.
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
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The subject or, when applicable, the subject's legally acceptable representative signs and dates a written informed consent form and any required privacy authorisation prior to the initiation of any study procedures.
- •The subject is aged 18 to 80 years inclusive.
- •The subject has a good understanding of the Dutch language.
- •The subject is diagnosed with moderately to severely active ulcerative colitis or Crohn's disease, confirmed by clinical, endoscopic, histological, and/or imaging criteria.
- •The subject was in maintenance therapy, later lost their response to treatment and subsequently gained steroid-free, clinical and biological remission following infliximab dose escalation (i.e., by increasing the dose and/or shortening the dosing interval) and had an infliximab trough concentration ≥5 mg/L.
- •Adequate contraception in female subjects of reproductive age (oral contraception, intra-uterine device, sterilisation or barrier method).
排除标准
- •The subject is aged <18 years or >80 years.
- •The subject receives infliximab prophylactically (e.g. in the immediate postoperative setting).
- •The subject has an ostomy or an ileal anal pouch anastomosis.
- •If female subjects, when pregnant (based on a positive serum sample) or lactating or intending to become pregnant or nurse before, during or within 15 weeks after the last dose of study drug; or intending to donate ova during such time period.
- •The subject is participating in another interventional clinical trial.
研究组 & 干预措施
Interventional arm
Model-informed precision dosing of infliximab (intravenously administered) using a Bayesian forecasting software tool. Doses and dosing intervals will be derived from the software tool, aiming to maintain adequate exposure (trough concentration target 5 mg/L).
干预措施: Infliximab (Drug)
Historical control arm
The treating physician adjusted the intravenously administered infliximab doses and dosing intervals without being guided by a model-informed precision dosing software tool. The primary objective was to extend the dosing interval. Therefore, dose de-escalation (interval extension with/without dose adjustment) were performed following a scheme at the treating physician's discretion.
干预措施: Infliximab (Drug)
结局指标
主要结局
Steroid-free, combined clinical and biological remission
时间窗: During one year after start of infliximab dose de-escalation
The proportion of patients maintaining steroid-free, combined clinical and biological remission during one year after infliximab dose de-escalation based on a standard dosing algorithm versus a model-informed dosing algorithm. Combined clinical and biological remission is defined based on patient-reported outcomes (rectal bleeding score = 0 + stool frequency score ≤1 \[ulcerative colitis\], mean daily abdominal pain score ≤1 + liquid stool frequency score ≤1.5 \[Crohn's disease\]) together with normal C-reactive protein (\<5 mg/L) and faecal calprotectin (\<250 mg/kg). Steroid-free indicates the absence of any dose of any oral or rectal steroid use.
次要结局
- Steroid-free, combined clinical and biological remission(At one year after start of infliximab dose de-escalation)