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| ID | Type | Description | Link |
|---|---|---|---|
| 2024-515358-25-00 | EU Trial (CTIS) Number |
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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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 4.5 mg risankizumab-800CW | Experimental | Patients receive 4.5 mg risankizumab-800CW and undergo a Fluorescence Molecular Imaging procedure |
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| 15 mg risankizumab-800CW | Experimental | Patients receive 15 mg risankizumab-800CW and undergo a Fluorescence Molecular Imaging procedure |
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| 25 mg risankizumab-800CW | Experimental | Patients receive 25 mg risankizumab-800CW and undergo a Fluorescence Molecular Imaging procedure |
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| 14 weeks or more of risankizumab therapy and optimal dose risankizumab-800CW | Experimental | 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 |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Risankizumab-800CW 4.5 mg | Drug | Risankizumab-800CW will be administered intravenously. 2-3 days later, a Fluorescence Molecular Imaging procedure will be performed to enable the visualisation and detection of fluorescence signals. |
| Measure | Description | Time Frame |
|---|---|---|
| Determine the safety of risankizumab-800CW in IBD | Evaluating possible (severe) adverse events (SAE and AEs) | 2-3 days after administration (day of FME procedure) |
| Blood pressure | Systolic and diastolic in millimeters of mercure (mmHg) | Five minutes before, and five and sixty minutes after tracer administration |
| Heart rate | Beats per minute | Five minutes before, and five and sixty minutes after tracer administration |
| Temperature | Degrees Celsius | Five minutes before, and five and sixty minutes after tracer administration |
| Investigate the feasibility of using ex vivo FMI to detect risankizumab-800CW | 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. | 12 months |
| Investigate the feasibility of using FME to detect risankizumab-800CW signals_1 | Evaluating the performance of FME for detecting risankizumab-800CW signals. This evaluation will be based on MDSFR/SFF measurements. | 12 months |
| Investigate the feasibility of using FME to detect risankizumab-800CW signals_2 | 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). |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 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 | 12 months |
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Inclusion Criteria for part A:
Inclusion Criteria for part B:
Exclusion Criteria for part A:
Exclusion Criteria for part B:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Wouter B Nagengast, MD, PharmD, PhD | Contact | +31(0)503612620 | w.b.nagengast@umcg.nl |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Medical Center Groningen | Recruiting | Groningen | 9713GZ | Netherlands |
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| ID | Term |
|---|---|
| D003093 | Colitis, Ulcerative |
| D003424 | Crohn Disease |
| D015212 | Inflammatory Bowel Diseases |
| ID | Term |
|---|---|
| D003092 | Colitis |
| D005759 | Gastroenteritis |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
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| Risankizumab-800CW 15 mg | Drug | Risankizumab-800CW will be administered intravenously. 2-3 days later, a Fluorescence Molecular Imaging procedure will be performed to enable the visualisation and detection of fluorescence signals. |
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| Risankizumab-800CW 25 mg | Drug | Risankizumab-800CW will be administered intravenously. 2-3 days later, a Fluorescence Molecular Imaging procedure will be performed to enable the visualisation and detection of fluorescence signals. |
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| Risankizumab-800CW optimal dose | Drug | Risankizumab-800CW will be administered intravenously. 2-3 days later, a Fluorescence Molecular Imaging procedure will be performed to enable the visualisation and detection of fluorescence signals. |
|
| 12 months |
| Investigate the feasibility of using FME to detect risankizumab-800CW signals_3 | Evaluating the performance of FME for detecting risankizumab-800CW signals. This evaluation will be based on TBR/CNR calculations. | 12 months |
| Determining the optimal imaging dose of risankizumab-800CW | The optimal dose will be based on the risankizumab-800CW signals during FME and ex vivo FMI | 12 months |
| 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 | 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 | 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 | 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? | 12 months |
| To correlate ex vivo fluorescence signals to inflammation severity and tracer dose based on histopathological examination inside the obtained biopsies | 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 | 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 risankizumab mucosal target cells | 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 | 12 months |
| D003108 |
| Colonic Diseases |
| D007410 | Intestinal Diseases |