Fluorescence Imaging of Risankizumab-800CW in Inflammatory Bowel Disease
- Conditions
- Ulcerative Colitis (UC)Crohn Disease (CD)
- Interventions
- Drug: Risankizumab-800CW 4.5 mgDrug: Risankizumab-800CW 15 mgDrug: Risankizumab-800CW 25 mgDrug: Risankizumab-800CW optimal dose
- Registration Number
- NCT06606808
- Lead Sponsor
- University Medical Center Groningen
- Brief Summary
Crohn\'s Disease (CD) and Ulcerative Colitis (UC) are chronic inflammatory bowel diseases (IBD). Risankizumab is a human monoclonal antibody against IL23 p19, part of a pro-inflammatory cytokine that mediates the inflammatory response in IBD upon binding to its receptor. Primary non-response to risankizumab is high in both CD and UC. Currently, there are no predictors of response to risankizumab and the actual mechanism of action has not yet been elucidated. To gain better understanding of the drug targeting of risankizumab in IBD, the University Medical Center Groningen (UMCG) developed fluorescently labeled risankizumab (risankizumab-800CW). This study aims to assess the safety and the optimal dose of risankizumab-800CW 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 18
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description 4.5 mg risankizumab-800CW Risankizumab-800CW 4.5 mg Patients receive 4.5 mg risankizumab-800CW and undergo a Fluorescence Molecular Imaging procedure 15 mg risankizumab-800CW Risankizumab-800CW 15 mg Patients receive 15 mg risankizumab-800CW and undergo a Fluorescence Molecular Imaging procedure 25 mg risankizumab-800CW Risankizumab-800CW 25 mg Patients receive 25 mg risankizumab-800CW and undergo a Fluorescence Molecular Imaging procedure 14 weeks or more of risankizumab therapy and optimal dose risankizumab-800CW Risankizumab-800CW optimal dose Patients who are treated with risankizumab for at least 14 weeks are enrolled in this arm. This can be patients who already joined in the dose finding part of the study or new patients. These patients will receive the optimal dose risankizumab-800CW and will undergo aFluorescence Molecular Imaging procedure
- Primary Outcome Measures
Name Time Method Determine the safety of risankizumab-800CW in IBD 2-3 days after administration (day of FME procedure) Evaluating possible (severe) adverse events (SAE and AEs)
Blood pressure Five minutes before, and five and sixty minutes after tracer administration Systolic and diastolic in millimeters of mercure (mmHg)
Heart rate Five minutes before, and five and sixty minutes after tracer administration Beats per minute
Temperature Five minutes before, and five and sixty minutes after tracer administration Degrees Celsius
Investigate the feasibility of using ex vivo FMI to detect risankizumab-800CW 12 months Evaluating the performance of ex vivo FMI for detecting risankizumab-800CW signals. This evaluation will be based on mean fluorescence intensities (MFIs) of biopsies and fluorescence/light sheet microscopy.
Investigate the feasibility of using FME to detect risankizumab-800CW signals_1 12 months Evaluating the performance of FME for detecting risankizumab-800CW signals. This evaluation will be based on MDSFR/SFF measurements.
Investigate the feasibility of using FME to detect risankizumab-800CW signals_2 12 months Evaluating the performance of FME for detecting risankizumab-800CW signals. This evaluation will be based on a visual evaluation during FME (visible signal yes/no).
Investigate the feasibility of using FME to detect risankizumab-800CW signals_3 12 months Evaluating the performance of FME for detecting risankizumab-800CW signals. This evaluation will be based on TBR/CNR calculations.
Determining the optimal imaging dose of risankizumab-800CW 12 months The optimal dose will be based on the risankizumab-800CW signals during FME and ex vivo FMI
- Secondary Outcome Measures
Name Time Method Investigate a potential correlation of in vivo fluorescence signal intensities and target saturation to clinical response/remission after 14 weeks of risankizumab therapy regimen in patients with IBD 12 months Evaluation of the potential correlation in vivo will be based on in vivo fluorescence images and the MDSFR/SFF measurements before and after at least 14 weeks of risankizumab treatment
Investigate a potential correlation of ex vivo fluorescence signal intensities and target saturation to clinical response/remission after 14 weeks of risankizumab therapy regimen in patients with IBD 12 months Evaluation of the potential correlation ex vivo will be based on MFIs of biopsies, fluorescence microscopy results, and tracer concentrations inside biopsies before and after at least 14 weeks of risankizumab treatment
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 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?
To correlate ex vivo fluorescence signals to inflammation severity and tracer dose based on histopathological examination inside the obtained biopsies 12 months 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
To assess tracer stability, tracer distribution and tracer concentration, and to identify the composition of immune cells ex vivo to learn more about risankizumab mucosal target cells 12 months Fluorescence (confocal) microscopy with additional use of immune panels and spatial transcriptomics analysis (before and after at least 14 weeks of risankizumab treatment). Measurements of the risankizumab-800CW concentration by light-sheet microscopy after tissue clearing, insights in risankizumab target cells and presence of immune cells inside the biopsies and blood samples by flow cytometry and assessment of tracer stability by Western Blot
Trial Locations
- Locations (1)
University Medical Center Groningen
🇳🇱Groningen, Netherlands