Fluorescence Imaging of Risankizumab-800CW in Inflammatory Bowel Disease

NCT06606808 | Recruiting Phase 1

• 2 other identifiers: UMCG 200102024-515358-25-00
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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).

Conditions

Ulcerative Colitis (UC); Crohn Disease (CD)

Keywords

Fluorescence Molecular Endoscopy; Inflammatory Bowel Disease; Risankizumab-800CW

Outcome Measures

Primary Outcomes (9)

• 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).

  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 Outcomes (5)

• 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

Study Arms (4)

4.5 mg risankizumab-800CW

EXPERIMENTAL

Patients receive 4.5 mg risankizumab-800CW and undergo a Fluorescence Molecular Imaging procedure

Drug: Risankizumab-800CW 4.5 mg

15 mg risankizumab-800CW

EXPERIMENTAL

Patients receive 15 mg risankizumab-800CW and undergo a Fluorescence Molecular Imaging procedure

Drug: Risankizumab-800CW 15 mg

25 mg risankizumab-800CW

EXPERIMENTAL

Patients receive 25 mg risankizumab-800CW and undergo a Fluorescence Molecular Imaging procedure

Drug: Risankizumab-800CW 25 mg

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

Drug: Risankizumab-800CW optimal dose

Interventions

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.

4.5 mg risankizumab-800CW

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.

15 mg risankizumab-800CW

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.

25 mg risankizumab-800CW

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.

14 weeks or more of risankizumab therapy and optimal dose risankizumab-800CW

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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)
• 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)

Sponsors & Collaborators

• University Medical Center Groningen: lead

Study Sites (1)

University Medical Center Groningen

Groningen, 9713GZ, Netherlands

RECRUITING

MeSH Terms

Conditions

Colitis, Ulcerative; Crohn Disease; Inflammatory Bowel Diseases

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Colonic Diseases; Intestinal Diseases

Central Study Contacts

Wouter B Nagengast, MD, PharmD, PhD

CONTACT

+31(0)503612620; w.b.nagengast@umcg.nl

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 10, 2024
• First Posted: September 23, 2024
• Study Start: November 8, 2024
• Primary Completion: August 1, 2025
• Study Completion: December 1, 2025
• Last Updated: March 5, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)