Clinical trial NCT04112212: Using Vedolizumab-800CW to Gain Insight Into Local Drug Distribution and Mucosal Target Cells in IBD Patients
Official title: Using Fluorescently Labeled Vedolizumab to Visualize Local Drug Distribution During Colonoscopy and Identify Mucosal Target Cells in Patients With Inflammatory Bowel Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Crohn Disease
Colitis, Ulcerative
Keywords: Fluorescence
Endoscopy
Vedolizumab-800CW
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
First posted: 2019-10-02
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: 38 IBD patients were included in the study.

1. Dose escalation, including 3 dose groups.
2. Adding a blocking dose.
3. Patients included after \>14 weeks of therapy
Primary purpose: OTHER

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.


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

Primary outcomes:
measure: Fluorescent signal in patients with IBD
timeFrame: After 18 months when study is completed.
Secondary outcomes:
measure: Safety of Vedolizumab-800CW in patients with IBD
timeFrame: 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.
measure: Semi-quantifying fluorescent signals in patients with IBD
timeFrame: Interim analysis after 30 weeks (at least 5 patients included). Complete data after 18 months when study is completed.
measure: FMI ex vivo analysis to detect target cells
timeFrame: After 18 months when study is completed.
measure: Distribution of Vedolizumab in the inflamed gut
timeFrame: After 18 months when study is completed.
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
Study officials:
affiliation: University Medical Center Groningen
name: W.B. Nagengast, MD, PhD, PharmD
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: 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.