RISANKIZUMAB for Inflammatory bowel disease|Ulcerative colitis|Crohn's disease

Inclusion criteria

• {"criterion_text":"- Established IBD diagnosis (UC or CD).\n- Active disease: clinically active disease of the bowel is defined clinically as at least mild activity using dedicated scoring indices or biochemically active disease as defined by a fecal calprotectin > 60 µg/g\n- Patients must be eligible for risankizumab therapy.\n- Age of 18 years.\n- Written informed consent.\n- Clinical indication for an endoscopic procedure.\n- For female subject who are of childbearing potential, are premenopausal with intact reproductive organs, or are less than 2 years postmenopausal, a negative pregnancy test (urine or blood test) must be available."}

Exclusion criteria

• {"criterion_text":"- A female study patient who is pregnant or provides breastfeeding\n- A female study patient of premenopausal age who does not use any reliable form of contraception at the time of risankizumab-800CW administration and the following 10 weeks\n- Medical or psychiatric conditions that compromise the patient’s ability to give informed consent\n- Prior anti-IL23-specific therapy (IL23/IL12 combination therapy is not an exclusion criteria)\n- Active extra gastrointestinal manifestations of Crohn’s disease (e.g. uveitis or pyoderma gangrenosum at vital locations)"}

Primary endpoints

• {"endpoint_text":"- Monitoring of the vital signs before and after tracer administration and evaluating possible (severe) adverse events (SAE & AEs).","definition_or_measurement_approach":"Monitoring of vital signs before and after tracer administration; recording and evaluation of AEs, SAEs and SUSARs."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"In vivo visual assessment during fluorescence molecular endoscopy (visible signal yes/no), calculation of target-to-background ratio (TBR) and contrast-to-noise ratio (CNR), quantification of mean fluorescence intensities (MFIs) in biopsies, MDSFR/SFF spectroscopy measurements and ex vivo fluorescence/light sheet microscopy analyses."}

Secondary endpoints

• {"endpoint_text":"- Analysis of in vivo fluorescence images and quantification of fluorescence signals in real-time with spectroscopy, and compare this to endoscopic/histologic inflammation score. We semi-quantify the fluorescence signal in FFPE-biopsies of mucosal tissue. These measurements are compared to the in vivo results of the same bowel section. For patients on treatment, we will look for a possible correlation of in and ex vivo quantified fluorescence and endoscopic/histologic response to risankizumab.","definition_or_measurement_approach":"Real-time spectroscopy quantification of in vivo fluorescence images compared to endoscopic and histologic inflammation scores; semi-quantification of fluorescence in FFPE mucosal biopsies and correlation with in vivo measures and clinical response to risankizumab."}
• {"endpoint_text":"- Fluorescence signal will be quantified by spectroscopy during endoscopy in all FME inspected bowel segments. The measurements will be compared within all dose groups to determine the optimal dose. Furthermore, spectroscopy measurements will be correlated with fluorescence intensities visualized using the FME camera. Finally, these measurements will be compared with inflammation severity to draw any conclusions about risankizumab distribution into inflamed or non-inflamed tissue.","definition_or_measurement_approach":"Spectroscopy-based quantification of fluorescence across inspected bowel segments, comparisons across dose groups to identify optimal imaging dose, correlation between spectroscopy and FME camera intensities, and comparison with inflammation severity metrics."}
• {"endpoint_text":"- In vivo and ex vivo spectroscopy measurements will be plotted against tracer dose and endoscopic/histopathological inflammation scores. The gastroenterologist evaluates the endoscopic inflammation score during the endoscopy. The histopathological score is determined by an expert pathologist based on an H&E staining of the FFPE biopsies. We hypothesize a positive correlation between the fluorescence signal and the tracer dose and between the fluorescence signal and the inflammation scores.","definition_or_measurement_approach":"Plotting and statistical correlation of in vivo/ex vivo spectroscopy measurements with tracer dose and endoscopic/histopathological inflammation scores (endoscopic evaluation by gastroenterologist; histopathological H&E scoring by expert pathologist)."}
• {"endpoint_text":"- SDS-PAGE with protein extracts of biopsies is used to prove that the fluorescence signal measured originated from the intact tracer. 3D ex vivo fluorescence analysis on biopsies is performed to assess the concentration of risankizumab-800CW in the intact biopsies. Fluorescence microscopy is performed to visualize the tracer signal and perform additional immunofluorescence staining for different immune cells to identify the immune cell type of risankizumab-800CW positive cells.","definition_or_measurement_approach":"Biochemical confirmation via SDS-PAGE of intact tracer in biopsy protein extracts; 3D ex vivo fluorescence quantification for tracer concentration; fluorescence microscopy and immunofluorescence staining to identify tracer-positive immune cell types."}

Netherlands

Earliest CTIS Part Ii Submission Date

21-08-2024

Latest Decision Or Authorization Date

05-09-2024

Processing Time Days

15

Number Of Sites

1

Number Of Participants

18

Primary sponsor

Full Name

Universitair Medisch Centrum Groningen

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands