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

Study Overview
=================
Brief 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.

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

Conditions
-----------------
Crohn Disease, Colitis, Ulcerative

Intervention / Treatment
-----------------
* Drug: Fluorescence molecular imaging procedure using vedolizumab-800CW
* Other: Fluorescence molecular imaging procedure without prior administration of vedolizumab-800CW
* Combination Product: Fluorescence molecular imaging procedure using vedolizumab-800CW with prior administration of unlabeled vedolizumab


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: 38 IBD patients were included in the study. Dose escalation, including 3 dose groups. Adding a blocking dose. Patients included after >14 weeks of therapy
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: No administration of vedolizumab-800CW<br>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<br>* Fluorescence molecular imaging was performed to enable the visualization and detection of fluorescence signals.<br>* Other names: Control group;|
| Experimental: 4.5 mg vedolizumab-800CW group<br>Patients received 4.5 mg vedolizumab-800CW and subsequently underwent a Fluorescence molecular imaging procedure | Drug: Fluorescence molecular imaging procedure using vedolizumab-800CW<br>* 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.<br>|
| Experimental: 15 mg vedolizumab-800CW group<br>Patients received 15 mg vedolizumab-800CW and subsequently underwent a Fluorescence molecular imaging procedure | Drug: Fluorescence molecular imaging procedure using vedolizumab-800CW<br>* 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.<br>|
| Experimental: 75 mg vedolizumab + 15 mg vedolizumab-800CW group<br>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<br>* 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.<br>|
| Experimental: 300mg vedolizumab + 15mg vedolizumab-800CW group<br>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<br>* 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.<br>|
| Experimental: > 14 weeks of vedolizumab therapy + 15 mg vedolizumab-800CW group<br>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<br>* 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.<br>|

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 |
| --- | --- | --- |
| 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. | 
| Distribution of Vedolizumab in the inflamed gut | To assess the (sub-)cellular location of vedolizumab-800CW microscopically. | After 18 months when study is completed. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Fluorescence, Endoscopy, Vedolizumab-800CW