Crohn Disease (CD), Ulcerative Colitis (UC)
Conditions
Keywords
Fluorescence Molecular Endoscopy, Inflammatory Bowel Disease, Risankizumab-800CW
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).
Interventions
DRUGRisankizumab-800CW 4.5 mg
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.
DRUGRisankizumab-800CW 15 mg
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.
DRUGRisankizumab-800CW 25 mg
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.
DRUGRisankizumab-800CW optimal dose
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.
Sponsors
University Medical Center Groningen
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
for part A: * Established IBD diagnosis * 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 * Patients must be eligible for risankizumab therapy * Minimum age of 18 years * Written informed consent * Clinical indication for an endoscopic procedure Inclusion Criteria for part B: * Established IBD diagnosis * Patients must be on risankizumab therapy for at least 14 weeks * Minimum age of 18 years * Written informed consent * Clinical indication for an endoscopic procedure
Exclusion criteria
for part A: * A female study patient who is pregnant or provides breastfeeding * 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 * Medical or psychiatric conditions that compromise the patient's ability to give informed consent * Prior anti-IL23-specific therapy (IL23/IL12 combination therapy is not an
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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. |
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
Countries
Netherlands
Contacts
Primary ContactWouter B Nagengast, MD, PharmD, PhD
Outcome results
None listed