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
- 2 期
- 状态
- 招募中
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Monitoring of the vital signs before and after tracer administration and evaluating possible (severe) adverse events (SAE & AEs). Visual evaluation during FME (visible signal yes/no), TBR and CNR calculations, mean fluorescence intensities (MFIs) of biopsies, MDSFR/SFF measurements and fluorescence/ light sheet microscopy.
研究概览
简要总结
To evaluate the safety of adalimumab-680LT through monitoring vital signs, the injection site and evaluating possible tracer-related (severe) adverse events (SAE/AEs) and suspected unexpected serious adverse reactions (SUSARs). To investigate the feasibility of using fluorescence molecular endoscopy (FME) and ex vivo FMI to detect adalimumab-680LT signals and to determine their most optimal imaging dose.
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
- •Established IBD diagnosis (UC or CD)
- •Active disease: clinically active disease of the bowel is defined clinically as at least mild activity using dedicated scoring indices and biochemically active disease as defined by a fecal calprotectin > 60 µg/g (measurement within the last 6 weeks before inclusion
- •Patients must be eligible for adalimumab therapy
- •Age of 18 years
- •Written informed consent.
- •Clinical indication for an endoscopic procedure
排除标准
- •A female study patient who is pregnant or provides breastfeeding will be excluded from participation in this study
- •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
- •A female study 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
- •Active extra gastrointestinal manifestations of Crohn’s disease (e.g. uveitis or pyoderma gangrenosum at vital locations)
- •Previous treatment with adalimumab and detectable anti-adalimumab antibodies levels
结局指标
主要结局
Monitoring of the vital signs before and after tracer administration and evaluating possible (severe) adverse events (SAE & AEs). Visual evaluation during FME (visible signal yes/no), TBR and CNR calculations, mean fluorescence intensities (MFIs) of biopsies, MDSFR/SFF measurements and fluorescence/ light sheet microscopy.
Monitoring of the vital signs before and after tracer administration and evaluating possible (severe) adverse events (SAE & AEs). Visual evaluation during FME (visible signal yes/no), TBR and CNR calculations, mean fluorescence intensities (MFIs) of biopsies, MDSFR/SFF measurements and fluorescence/ light sheet microscopy.
次要结局
- Comparison of in vivo fluorescence images, MFIs of biopsies, the MDSFR/SFF measurements, fluorescence microscopy results, and tracer concentrations inside biopsies before and after at least 14 weeks of adalimumab treatment.
- Quantification of MDSFR/SFF measurements in inflamed tissue compared to measurements in non-inflamed tissue. Positive correlation between MDSFR/SFF measurements and dose/inflammation severity?
- Histologically ascertained tissue types (qualitative): • Normal (non-inflamed) ileal, colon and rectal tissue. • Inflamed ileum, colon and rectum tissue. • Random ‘’high-fluorescent’’ tissue • Random ‘’Non-fluorescent’’ tissue
- Fluorescence (confocal) microscopy with additional use of immune panels and spatial transcriptomics analysis (before and after at least 14 weeks of adalimumab treatment). Measurements of the adalimumab-680LT concentration by light-sheet microscopy after tissue clearing, insights in adalimumab-target cells and presence of immune cells inside the biopsies and blood samples by flow cytometry and assessment of tracer stability by Western Blot.
研究者
Wouter B. Nagengast
Scientific
Universitair Medisch Centrum Groningen