Fluorescence Imaging of Risankizumab-800CW in Inflammatory Bowel Disease (NAVIGATE)

Investigating the Safety, Feasibility, and Optimal Dose of Risankizumab-800CW for Visualizing Drug Targeting in Inflammatory Bowel Disease

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).

Study Overview

• Status: Recruiting
• Conditions: Crohn Disease (CD); Ulcerative Colitis (UC)
• Intervention / Treatment: Drug: Risankizumab-800CW 4.5 mg; Drug: Risankizumab-800CW 15 mg; Drug: Risankizumab-800CW 25 mg; Drug: Risankizumab-800CW optimal dose

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Wouter B Nagengast, MD, PharmD, PhD; Phone Number: +31(0)503612620; Email: w.b.nagengast@umcg.nl

Study Locations

• Netherlands
  • Groningen, Netherlands, 9713GZ
    • Recruiting
    • University Medical Center Groningen
    • Contact: Wouter B Nagengast, MD, PharmD, PhD; Phone Number: +31(0)503612620; Email: w.b.nagengast@umcg.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 exclusion criteria)
• Active extra gastrointestinal manifestations of Crohn's disease (e.g. uveitis or pyoderma gangrenosum at vital locations)

Exclusion Criteria for part B:

• 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
• Active extra gastrointestinal manifestations of Crohn's disease (e.g. uveitis or pyoderma gangrenosum at vital locations)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 4.5 mg risankizumab-800CW; Patients receive 4.5 mg risankizumab-800CW and undergo a Fluorescence Molecular Imaging procedure	Drug: Risankizumab-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.
Experimental: 15 mg risankizumab-800CW; Patients receive 15 mg risankizumab-800CW and undergo a Fluorescence Molecular Imaging procedure	Drug: Risankizumab-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.
Experimental: 25 mg risankizumab-800CW; Patients receive 25 mg risankizumab-800CW and undergo a Fluorescence Molecular Imaging procedure	Drug: Risankizumab-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.
Experimental: 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	Drug: Risankizumab-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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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).	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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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

Collaborators and Investigators

• Sponsor: University Medical Center Groningen

Study record dates

Study Major Dates

• Study Start (Actual): November 8, 2024
• Primary Completion (Estimated): August 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: September 10, 2024
• First Submitted That Met QC Criteria: September 19, 2024
• First Posted (Actual): September 23, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 4, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Inflammatory Bowel Disease; Fluorescence Molecular Endoscopy; Risankizumab-800CW
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Crohn Disease; Intestinal Diseases; Inflammatory Bowel Diseases; Immunologic Factors; Physiological Effects of Drugs; Antibodies, Monoclonal
• Other Study ID Numbers: UMCG 20010; 2024-515358-25-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No