NIR FME of Labelled Vedolizumab to Elucidate the Mechanism of Action and Predicting Response in IBD Patients. (VISION)

• ClinicalTrials.gov Identifier: NCT04112212
• Recruitment Status: Recruiting
• First Posted: October 2, 2019
• Last Update Posted: April 28, 2021
• Sponsor: University Medical Center Groningen
• Information provided by (Responsible Party): dr. W.B. Nagengast, MD, University Medical Center Groningen

Study Description

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 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

Detailed Description:

See brief summary

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 35 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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

Arms and Interventions

Arm

Intervention/treatment

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).

Drug: Vedolizumab-800CW; 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.

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. 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.

2. 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.
3. 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).
4. 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.
5. 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.

Eligibility Criteria

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

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

Contacts and Locations

Contacts

Contact: W.B. Nagengast, MD, PhD, PharmD; +31503612620; w.b.nagengast@umcg.nl

Contact: R.Y. Gabriels, MSc, MD; +31615691998; r.y.gabriels@umcg.nl

Locations

Netherlands

University Medical Center Groningen; Recruiting

Groningen, Netherlands, 9713 GZ

Contact: W B Nagengast, MD, PhD, PharmD +31503612620 w.b.nagengast@umcg.nl

Sponsors and Collaborators

University Medical Center Groningen

Investigators

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

More Information

Publications:

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.

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.

• Responsible Party: dr. W.B. Nagengast, MD, Principal Investigator, University Medical Center Groningen
• ClinicalTrials.gov Identifier: NCT04112212
• Other Study ID Numbers: NL69572.042.19
• First Posted: October 2, 2019
• Last Update Posted: April 28, 2021
• Last Verified: April 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by dr. W.B. Nagengast, MD, University Medical Center Groningen:

Fluorescence; Endoscopy; Vedolizumab-800CW

Additional relevant MeSH terms:

Crohn Disease; Colitis, Ulcerative; Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Colitis; Colonic Diseases; Vedolizumab; Gastrointestinal Agents