NIR FME of Labelled Vedolizumab to Elucidate the Mechanism of Action and Predicting Response in IBD Patients. (VISION)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04112212|
Recruitment Status : Recruiting
First Posted : October 2, 2019
Last Update Posted : April 28, 2021
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 near-infrared fluorescence molecular endoscopy (NIR-FME), spectroscopy and confocal laser endomicroscopy (CLE). By gaining insight into local vedolizumab concentrations, drug distribution and by discovering target cells, we expect to gain insight into the mechanism of action, gather data with which to optimize vedolizumab dosing, and to learn to predict therapy response in the individual patient.
|Condition or disease||Intervention/treatment||Phase|
|Crohn Disease Colitis, Ulcerative||Drug: Vedolizumab-800CW Device: Fluorescence endoscopy and spectroscopy||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||35 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Near-infrared Fluorescence Molecular Endoscopy Imaging of Labelled Vedolizumab-800CW to Elucidate the Mechanism of Action and Predicting Response in IBD Patients. A Prospective Pilot Intervention Study:|
|Actual Study Start Date :||November 4, 2020|
|Estimated Primary Completion Date :||December 1, 2021|
|Estimated Study Completion Date :||December 30, 2021|
Experimental: IV administration of vedolizumab-800CW
The tracer will be intraveniously administrered 2 or 3 days before the colonoscopy procedure (with the near infrared fluorescence endoscopy platform).
Intraveniously administration of vedolizumab-800CW.
Device: Fluorescence endoscopy and spectroscopy
Molecular Fluorescence Endoscopy platform A flexible fluorescence fiber-bundle is attached to a fluorescence camera platform to enable the detection of fluorescence signals. The fluorescence fiber-probe is inserted through the standard working channel of the standard clinical endoscope.
- Fluorescent signal in patients with IBD [ Time Frame: After 18 months when study is completed. ]Quantification of fluorescent signal after a microdose of vedolizumab-800CW in inflamed and non-inflamed tissue in patients with IBD.
- Safety of Vedolizumab-800CW in patients with IBD [ Time Frame: Interim analysis after 30 weeks (at least 5 patients included). Complete data after 18 months when study is completed. ]
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.
- Quantifying fluorescent signals in patients with IBD [ Time Frame: Interim analysis after 30 weeks (at least 5 patients included). Complete data after 18 months when study is completed. ]- Quantify the in vivo NIR fluorescent signal of vedolizumab-800CW by means of the MDSFR/SFF spectroscopy probe.
- FME Ex Vivo analysis to detect target cells [ Time Frame: After 18 months when study is completed. ]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).
- Distribution of Vedolizumab in the inflamed gut [ Time Frame: After 18 months when study is completed. ]To assess the (sub-)cellular location of vedolizumab-800CW microscopically.
- Elucidate vedolizumab target cells [ Time Frame: After 18 months when study is completed. ]Identify specific vedolizumab target cells using CITE-seq for single-cell RNA sequencing.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04112212
|Contact: W.B. Nagengast, MD, PhD, PharmDemail@example.com|
|Contact: R.Y. Gabriels, MSc, MDfirstname.lastname@example.org|
|University Medical Center Groningen||Recruiting|
|Groningen, Netherlands, 9713 GZ|
|Contact: W B Nagengast, MD, PhD, PharmD +31503612620 email@example.com|
|Principal Investigator:||W.B. Nagengast, MD, PhD, PharmD||University Medical Center Groningen|