Investigating the Safety, Feasibility, and Optimal Dose of Risankizumab-800CW for Visualizing Drug Targeting in Inflammatory Bowel Disease
Overview
- Phase
- Phase 1
- Intervention
- Risankizumab-800CW 4.5 mg
- Conditions
- Ulcerative Colitis (UC)
- Sponsor
- University Medical Center Groningen
- Enrollment
- 18
- Locations
- 1
- Primary Endpoint
- Determine the safety of risankizumab-800CW in IBD
- Status
- Recruiting
- Last Updated
- last year
Overview
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).
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
4.5 mg risankizumab-800CW
Patients receive 4.5 mg risankizumab-800CW and undergo a Fluorescence Molecular Imaging procedure
Intervention: Risankizumab-800CW 4.5 mg
15 mg risankizumab-800CW
Patients receive 15 mg risankizumab-800CW and undergo a Fluorescence Molecular Imaging procedure
Intervention: Risankizumab-800CW 15 mg
25 mg risankizumab-800CW
Patients receive 25 mg risankizumab-800CW and undergo a Fluorescence Molecular Imaging procedure
Intervention: Risankizumab-800CW 25 mg
14 weeks or more of risankizumab therapy and optimal dose risankizumab-800CW
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
Intervention: Risankizumab-800CW optimal dose
Outcomes
Primary Outcomes
Determine the safety of risankizumab-800CW in IBD
Time Frame: 2-3 days after administration (day of FME procedure)
Evaluating possible (severe) adverse events (SAE and AEs)
Blood pressure
Time Frame: Five minutes before, and five and sixty minutes after tracer administration
Systolic and diastolic in millimeters of mercure (mmHg)
Heart rate
Time Frame: Five minutes before, and five and sixty minutes after tracer administration
Beats per minute
Temperature
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 12 months
The optimal dose will be based on the risankizumab-800CW signals during FME and ex vivo FMI
Secondary Outcomes
- 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)
- 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)
- 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)
- To correlate ex vivo fluorescence signals to inflammation severity and tracer dose based on histopathological examination inside the obtained biopsies(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(12 months)