Investigating the Safety, Feasibility, and Optimal Dose of Fluorescently Labeled Adalimumab-680LT for Visualizing Drug Targeting in Inflammatory Bowel Diseases
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 21
- 试验地点
- 1
- 主要终点
- Investigate the feasibility of using FME to detect adalimumab-680LT signals
研究概览
简要总结
Crohn's Disease (CD) and Ulcerative Colitis (UC) are chronic inflammatory bowel diseases (IBD). Adalimumab is a human monoclonal antibody against TNF-alpha, a pro-inflammatory cytokine that mediates the inflammatory response in IBD upon binding to the TNF receptors. Primary non-response to adalimumab is high in both CD and UC. Currently, there are no predictors of response to adalimumab and the actual mechanism of action has not yet been elucidated. To gain better understanding of the drug targeting of adalimumab in IBD, the University Medical Center Groningen (UMCG) developed fluorescently labeled adalimumab (adalimumab-680LT). This study aims to assess the safety and the optimal dose of adalimumab-680LT to visualize and potentially quantify the local drug concentration and predict treatment response in IBD patients using in vivo and ex vivo fluorescence molecular imaging (FMI).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Established IBD diagnosis (UC or CD)
- •Active disease (clinically defined as at least mild activity using dedicated scoring indices and biochemically defined by a fecal calprotectin > 60 µg/g, measured within the last 6 weeks before inclusion)
- •Patients must be eligible for adalimumab therapy
- •Clinical indication for an endoscopic procedure
- •Age: 18 years or older
- •Written informed consent
- •For female patients of premenopausal age with intact reproductive organs or who are less than 2 years postmenopausal, a negative pregnancy test must be available.
排除标准
- •Pregnancy or breast feeding
- •Female patient of premenopausal age who does not use any reliable form of contraception at the time of adalimumab-680LT administration and the following 10 weeks.
- •Medical or psychiatric conditions that compromise the patient's ability to give informed consent
- •Prior anti-TNF therapy in the last 6 weeks before inclusion
- •Active extra gastrointestinal manifestations of Crohn's disease
- •Previous treatment with adalimumab and detectable anti-adalimumab antibodies levels
研究组 & 干预措施
No administration of adalimumab-680LT
Patients did not receive adalimumab-680LT, but underwent a Fluorescence Molecular Imaging procedure to serve as a control group and compare results with patients receiving the tracer
干预措施: Control (Other)
4.5 mg adalimumab-680LT
Patients received 4.5 mg adalimumab-680LT and underwent a Fluorescence Molecular Imaging procedure
干预措施: Adalimumab-680LT (Drug)
15 mg adalimumab-680LT
Patients received 15 mg adalimumab-680LT and underwent a Fluorescence Molecular Imaging procedure
干预措施: Adalimumab-680LT (Drug)
25 mg adalimumab-680LT
Patients received 25 mg adalimumab-680LT and underwent a Fluorescence Molecular Imaging procedure
干预措施: Adalimumab-680LT (Drug)
>14 weeks of adalimumab therapy + optimal dose adalimumab-680LT
Patients who received the optimal dose during the first Fluorescence Molecular Imaging procedure are invited for a second procedure after at least 14 weeks of adalimumab therapy. They will receive the optimal dose adalimumab-680LT and will undergo another Fluorescence Molecular Imaging procedure
干预措施: Adalimumab-680LT (Drug)
结局指标
主要结局
Investigate the feasibility of using FME to detect adalimumab-680LT signals
时间窗: 12 months
Evaluating the performance of FME for detecting adalimumab-680LT signals. This evaluation will be based on a visual evaluation during FME (visible signal yes/no), TBR and CNR calculations and MDSFR/SFF measurements.
Temperature
时间窗: Five minutes before, and five and sixty minutes after tracer administration
Degrees Celsius
Blood pressure
时间窗: Five minutes before, and five and sixty minutes after tracer administration
Millimeters of mercure (mmHg)
Determining the optimal imaging dose of adalimumab-680LT
时间窗: 12 months
The optimal dose will be based on the adalimumab-680LT signals during FME and ex vivo FMI
Determine the safety of adalimumab-680LT in IBD
时间窗: Until 24 hours after administration
Evaluating possible (severe) adverse events (SAE \& AEs)
Heart rate
时间窗: Five minutes before, and five and sixty minutes after tracer administration
Beats per minute
Investigate the feasibility of using ex vivo FMI to detect adalimumab-680LT
时间窗: 12 months
Evaluating the performance of ex vivo FMI for detecting adalimumab-680LT signals. This evaluation will be based on mean fluorescence intensities (MFIs) of biopsies and fluorescence/light sheet microscopy.
次要结局
- Investigate a potential correlation of ex vivo fluorescence signal intensities and target saturation to clinical response/remission after 14 weeks of adalimumab therapy regimen in patients with IBD(12 months)
- To correlate ex vivo fluorescence signals to inflammation severity and tracer dose based on histopathological examination inside the obtained biopsies(12 months)
- Quantify the fluorescence signals of the tracer in vivo by using single-fiber reflectance/single-fiber fluorescence (MDSFR/SFF) spectroscopy and correlate these measurements to tracer dose, in vivo fluorescence intensities and inflammation severity(12 months)
- Investigate a potential correlation of in vivo fluorescence signal intensities and target saturation to clinical response/remission after 14 weeks of adalimumab therapy regimen in patients with IBD(12 months)
- To assess tracer stability, tracer distribution and tracer concentration, and to identify the composition of immune cells ex vivo to learn more about adalimumab mucosal target cells(12 months)
研究者
dr. W.B. Nagengast, MD
prof. dr.
University Medical Center Groningen