Subcutaneous Infliximab After A Previous Intravenous Dose Optimization
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 275
- 试验地点
- 18
- 主要终点
- The proportion of patients that maintain steroid-free clinical and biological remission by week 52 without treatment optimization after switch to subcutaneous infliximab.
研究概览
简要总结
To compare clinical and biological outcome between a regimen with subcutaneous infliximab every week and subcutaneous infliximab every other week among patients who were in clinical and biological remission with an optimized intravenous schedule when they switched to subcutaneous infliximab.
详细描述
Inflammatory bowel diseases (IBD) are a group of immune mediated disorders primarily targeting the gastro-intestinal tract and consist of two distinct phenotypes: Crohn's disease (CD) and ulcerative colitis (UC) that share similarities in both clinical presentation, pathophysiology and treatment. A small proportion of IBD patients cannot be correctly characterized in one of those categories and is referred to as IBD type unclassified (IBDU), which is often classified under UC for clinical research purposes. TNF inhibitors are one of the most frequently prescribed biological therapies and remain an important part of the therapeutic arsenal with international guidelines recommending their use in moderate-to-severe CD and UC when conventional treatments have failed.
Infliximab, a chimer monoclonal antibody against tumor necrosis factor (TNF), was the first anti-TNF agent to be approved for treating IBD as early as 1999. After losing its product patent in 2013, several biosimilars of infliximab have been commercialized including CT-P13. Originally only available in an intravenous (IV) formulation, a subcutaneous (SC) formulation of CT-P13 has been registered for treating moderate-to-severe CD and UC as well. However, many questions on the use of these subcutaneous formulations of infliximab in daily clinical practice remain unanswered, especially in patients who previously required IV dose optimization of infliximab.
The primary objective of the AMARETTO trial is to compare clinical and biological outcome between a regimen with SC infliximab every week and SC infliximab every other week among patients who were in clinical and biological remission with an optimized IV schedule when they switched to SC infliximab.
The secondary objectives of this study are:
- To compare treatment optimization and discontinuation between a regimen with SC inflixmab every week and SC infliximab every other week among patients who were in clinical and biological remission with an optimized IV schedule when they switched to infliximab SC.
- To evaluate the willingness and the experience of patients switching to SC infliximab.
- To compare clinical and biological outcome, as well as treatment optimization and discontinuation between a regimen with SC infliximab (every week or every other week) and IV infliximab among patients who were in clinical and biological remission with an optimized IV schedule.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non-randomized
- 主要目的
- Intravenous comparison group
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •Patients with a previously documented CD, UC, IBDU diagnosis confirmed by clinical , endoscopic, histological, and/or radiological criteria.
- •Males and females ≥18 years old
- •Patients must be in steroid-free clinical remission at Screening defined as a rectal bleeding score of 0 and a stool frequency score of ≤1 for patients with UC / IBDU, or an average daily abdominal pain score ≤1 and a liquid stool frequency score ≤2.8 for patients with CD (based on the 3 days before the screening visit, excluding the day of or the day before an eventual endoscopy with bowel preparation) and this without the need for any type of steroids in the previous eight weeks.
- •Patients must be in biological remission at screening defined as a CRP <10 mg/L and a fecal calprotectin <250 µg/g.
- •Patients receiving IV infliximab for at least 26 consecutive weeks.
- •Patients receiving a stable IV dosing schedule for at least 20 weeks.
- •Patients receiving an average IV infliximab per eight weeks based on the two most recent IV administrations of more than 8 mg/kg, but not more than 22 mg/kg.
- •Patients who speak and read fluently Dutch, French or English.
- •Patients who is able to voluntary give their written informed consent.
排除标准
- •Male or female < 18 years
- •Patients with an ileorectal anastomosis, an ileal pouch-anal anastomosis or an ostomy (transient or permanent)
- •Patients participating in an interventional clinical trial with an Investigational Medicinal Product (IMP) or device.
- •Patients previously treated with subcutaneous infliximab.
- •Patients with active perianal fistulizing disease.
- •Patients with microscopic colitis.
结局指标
主要结局
The proportion of patients that maintain steroid-free clinical and biological remission by week 52 without treatment optimization after switch to subcutaneous infliximab.
The proportion of patients that maintain steroid-free clinical and biological remission by week 52 without treatment optimization after switch to subcutaneous infliximab.
次要结局
- The proportion of patients that maintain steroid-free clinical and biological remission by week 52 with treatment optimization.
- The proportion of patients that maintain steroid-free clinical and biological remission by week 52 (with or without treatment optimization).
- The proportion of patients that maintain steroid-free clinical and biological remission by week 8, by week 24 (without treatment optimization).
- The proportion of patients that maintain steroid-free clinical remission by week 8, by week 24, by week 52 (without treatment optimization).
- The proportion of patients that maintain steroid-free biological remission by week 8, by week 24, by week 52 (without treatment optimization).
- The proportion of patients switching back to IV infliximab by week 8, by week 24, by week 52.
- Time to (objectified) clinical relapse (or treatment optimization or treatment discontinuation).
- Time to objectified clinical relapse (or treatment optimization or treatment discontinuation).
- Time to treatment optimization (or treatment discontinuation).
- Time to treatment discontinuation.
- Time to clinical relapse (patients that undergo treatment optimization or treatment discontinuation without clinical relapse will be regarded as lost to follow-up from that timepoint).
- Time to objective clinical relapse (patients that undergo treatment optimization or treatment discontinuation without objective clinical relapse will be regarded as lost to follow-up from that timepoint).
- Patients experience and satisfaction with switching to SC therapy by week 8, week 24, by week 52.
- The proportion of eligible patients willing to switch and effectively switching to SC therapy.
- Baseline characteristics linked to willingness of switching and effectively switching to SC therapy.
- Reasons for willing or not willing to switch to SC therapy.
- Reasons for treatment optimization (clinical disease activity, biological disease activity, endoscopic disease activity, radiological disease activity, and/or other).
- Reasons for treatment discontinuation (clinical disease activity, biological disease activity, endoscopic disease activity, radiological disease activity, adverse events, pregnancy, patient's request, and/or other).
- The number and type of (serious) adverse events by week 52.
研究者
Tom Holvoet
Scientific
Belgian IBD Research and Development