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

Crohn Disease Clinical Trial

— VISION  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04112212
• Other study ID #: NL69572.042.19
• Status: Completed
• Phase: Phase 1
• Start date: November 4, 2020
• Est. completion date: January 1, 2023

Study information

• Verified date: April 2024
• Source: University Medical Center Groningen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 38
• Est. completion date: January 1, 2023
• Est. primary completion date: October 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Colitis, Ulcerative
• Crohn Disease

Intervention

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.

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.

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.

Locations

Country	Name	City	State
Netherlands	University Medical Center Groningen	Groningen

Sponsors (1)

Lead Sponsor	Collaborator
University Medical Center Groningen

Country where clinical trial is conducted

Netherlands, 

References & Publications (2)

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.
Secondary	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.
Secondary	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.
Secondary	Distribution of Vedolizumab in the inflamed gut	To assess the (sub-)cellular location of vedolizumab-800CW microscopically.	After 18 months when study is completed.