Using Vedolizumab-800CW to Gain Insight Into Local Drug Distribution and Mucosal Target Cells in IBD Patients (VISION)

Using Fluorescently Labeled Vedolizumab to Visualize Local Drug Distribution During Colonoscopy and Identify Mucosal Target Cells in Patients With Inflammatory Bowel Disease

Summary Vision Study

Crohn's Disease (CD) and Ulcerative Colitis (UC) are chronic idiopathic inflammatory bowel diseases (IBD). Vedolizumab is a humanized monoclonal antibody against α4β7 integrin, capable of blocking the migration of several immune cells across endothelium expressing MAdCAM-1. Vedolizumab is expensive and primary non-response is high in both CD and UC. Currently there are no predictors of response to vedolizumab and the actual mechanism of action has not yet been elucidated. To clarify the mechanism of action and gain better understanding of the high primary non-response rates, the University Medical Center Groningen (UMCG) developed a tracer fluorescently labeling vedolizumab. This study aims to gain insight into vedolizumab distribution and concentrations in the gut. The current study aims to identify the vedolizumab target cells in the inflamed gut mucosa using quantitative fluorescence molecular imaging (FMI). By gaining insight into local vedolizumab concentrations, drug distribution and by discovering target cells, we expect to gain insight into the mechanism of action of vedolizumab.

Study Overview

• Status: Completed
• Conditions: Crohn Disease; Colitis, Ulcerative
• Intervention / Treatment: Other: Fluorescence molecular imaging procedure without prior administration of vedolizumab-800CW; Drug: Fluorescence molecular imaging procedure using vedolizumab-800CW; Combination product: Fluorescence molecular imaging procedure using vedolizumab-800CW with prior administration of unlabeled vedolizumab

Detailed Description

See brief summary

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • University Medical Center Groningen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Established diagnosis of IBD, or Ulcerative Colitis (UC) or Crohn's Disease (CD).
• Vedolizumab naïve and eligible for vedolizumab treatment.
• Age: 18 years or older.
• Written informed consent.

Exclusion Criteria:

• Prior vedolizumab treatment
• Vedolizumab contraindicated as therapy
• Pregnancy or breast feeding.
• Patients younger than 18 years old

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

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: No administration of vedolizumab-800CW; Patients did not receive vedolizumab-800CW but underwent a Fluorescence molecular imaging procedure to serve as a control group and compare results with patients receiving the tracer	Other: Fluorescence molecular imaging procedure without prior administration of vedolizumab-800CW; Fluorescence molecular imaging was performed to enable the visualization and detection of fluorescence signals.; Other Names: Control group
Experimental: 4.5 mg vedolizumab-800CW group; Patients received 4.5 mg vedolizumab-800CW and subsequently underwent a Fluorescence molecular imaging procedure	Drug: Fluorescence molecular imaging procedure using vedolizumab-800CW; First vedolizumab-800CW was administered intravenously. 2-4 days later a fluorescence molecular imaging procedure was performed to enable the visualization and detection of fluorescence signals.
Experimental: 15 mg vedolizumab-800CW group; Patients received 15 mg vedolizumab-800CW and subsequently underwent a Fluorescence molecular imaging procedure	Drug: Fluorescence molecular imaging procedure using vedolizumab-800CW; First vedolizumab-800CW was administered intravenously. 2-4 days later a fluorescence molecular imaging procedure was performed to enable the visualization and detection of fluorescence signals.
Experimental: 75 mg vedolizumab + 15 mg vedolizumab-800CW group; Patients received 75mg vedolizumab + 15 mg vedolizumab-800CW and subsequently underwent a Fluorescence molecular imaging procedure	Combination product: Fluorescence molecular imaging procedure using vedolizumab-800CW with prior administration of unlabeled vedolizumab; Patients on vedolizumab therapy received vedolizumab-800CW iv or patients first received an unlabeled dose of vedolizumab prior to the iv administration of vedolizumab-800CW. 2-4 days later a fluorescence molecular imaging procedure was performed to enable the visualization and detection of fluorescence signals.
Experimental: 300mg vedolizumab + 15mg vedolizumab-800CW group; Patients received 300mg vedolizumab + 15 mg vedolizumab-800CW and subsequently underwent a Fluorescence molecular imaging procedure	Combination product: Fluorescence molecular imaging procedure using vedolizumab-800CW with prior administration of unlabeled vedolizumab; Patients on vedolizumab therapy received vedolizumab-800CW iv or patients first received an unlabeled dose of vedolizumab prior to the iv administration of vedolizumab-800CW. 2-4 days later a fluorescence molecular imaging procedure was performed to enable the visualization and detection of fluorescence signals.
Experimental: > 14 weeks of vedolizumab therapy + 15 mg vedolizumab-800CW group; Patients received 300mg vedolizumab + 15 mg vedolizumab-800CW after >14 weeks vedolizumab therapy and subsequently underwent a Fluorescence molecular imaging procedure	Combination product: Fluorescence molecular imaging procedure using vedolizumab-800CW with prior administration of unlabeled vedolizumab; Patients on vedolizumab therapy received vedolizumab-800CW iv or patients first received an unlabeled dose of vedolizumab prior to the iv administration of vedolizumab-800CW. 2-4 days later a fluorescence molecular imaging procedure was performed to enable the visualization and detection of fluorescence signals.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fluorescent signal in patients with IBD	Quantification of fluorescent signal after a microdose of vedolizumab-800CW in inflamed and non-inflamed tissue in patients with IBD.	After 18 months when study is completed.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Distribution of Vedolizumab in the inflamed gut	To assess the (sub-)cellular location of vedolizumab-800CW microscopically.	After 18 months when study is completed.
Safety of Vedolizumab-800CW in patients with IBD	Collect safety data of vedolizumab-800CW. Checking vital parameters and adverse events caused by the drug or intervention. Register and analyze all AE's, SAE's and SUSAR's caused by vedolizumab-800CW.	Interim analysis after 30 weeks (at least 5 patients included). Complete data of all patients when study is completed. Individual patients were followed up for 1 week after vedolizumab-800CW injection for AE's, SAE's and SUSAR's.
Semi-quantifying fluorescent signals in patients with IBD	Semi-quantification of the ex vivo mean fluorescent intensity signal of vedolizumab-800CW in biopsies by calculating the mean fluorescence intensity (FImean) of biopsy images generated with a fluorescence flatbed scanner	Interim analysis after 30 weeks (at least 5 patients included). Complete data after 18 months when study is completed.
FMI ex vivo analysis to detect target cells	To evaluate the degree of in vivo fluorescence intensity for differences in severity of inflammation and quantify the in vivo NIR fluorescent signal of vedolizumab-800CW using the spectroscopy probe and compare this to the ex vivo fluorescent signal levels in the biopsies taken (immunohistochemistry, RNA and DNA analysis).	After 18 months when study is completed.

Collaborators and Investigators

• Sponsor: University Medical Center Groningen
• Investigators: Principal Investigator: W.B. Nagengast, MD, PhD, PharmD, University Medical Center Groningen

Publications and helpful links

General Publications

• Nagengast WB, Hartmans E, Garcia-Allende PB, Peters FTM, Linssen MD, Koch M, Koller M, Tjalma JJJ, Karrenbeld A, Jorritsma-Smit A, Kleibeuker JH, van Dam GM, Ntziachristos V. Near-infrared fluorescence molecular endoscopy detects dysplastic oesophageal lesions using topical and systemic tracer of vascular endothelial growth factor A. Gut. 2019 Jan;68(1):7-10. doi: 10.1136/gutjnl-2017-314953. Epub 2017 Dec 15. No abstract available.
• Tjalma JJJ, Koller M, Linssen MD, Hartmans E, de Jongh SJ, Jorritsma-Smit A, Karrenbeld A, de Vries EG, Kleibeuker JH, Pennings JP, Havenga K, Hemmer PH, Hospers GA, van Etten B, Ntziachristos V, van Dam GM, Robinson DJ, Nagengast WB. Quantitative fluorescence endoscopy: an innovative endoscopy approach to evaluate neoadjuvant treatment response in locally advanced rectal cancer. Gut. 2020 Mar;69(3):406-410. doi: 10.1136/gutjnl-2019-319755. Epub 2019 Sep 18. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): November 4, 2020
• Primary Completion (Actual): October 1, 2022
• Study Completion (Actual): January 1, 2023

Study Registration Dates

• First Submitted: September 25, 2019
• First Submitted That Met QC Criteria: September 29, 2019
• First Posted (Actual): October 2, 2019

Study Record Updates

• Last Update Posted (Actual): April 16, 2024
• Last Update Submitted That Met QC Criteria: April 14, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Endoscopy; Fluorescence; Vedolizumab-800CW
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Colitis; Crohn Disease; Colitis, Ulcerative; Gastrointestinal Agents; Vedolizumab
• Other Study ID Numbers: NL69572.042.19

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