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

NCT04112212 | Completed Phase 1 DMC

• 1 other identifier: NL69572.042.19
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

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.

Conditions

Crohn Disease; Colitis, Ulcerative

Keywords

Fluorescence; Endoscopy; Vedolizumab-800CW

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Safety of Vedolizumab-800CW in patients with IBD

  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

  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

  After 18 months when study is completed.

• Distribution of Vedolizumab in the inflamed gut

  After 18 months when study is completed.

Study Arms (6)

No administration of vedolizumab-800CW

OTHER

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

4.5 mg vedolizumab-800CW group

EXPERIMENTAL

Patients received 4.5 mg vedolizumab-800CW and subsequently underwent a Fluorescence molecular imaging procedure

Drug: Fluorescence molecular imaging procedure using vedolizumab-800CW

15 mg vedolizumab-800CW group

EXPERIMENTAL

Patients received 15 mg vedolizumab-800CW and subsequently underwent a Fluorescence molecular imaging procedure

Drug: Fluorescence molecular imaging procedure using vedolizumab-800CW

75 mg vedolizumab + 15 mg vedolizumab-800CW group

EXPERIMENTAL

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

300mg vedolizumab + 15mg vedolizumab-800CW group

EXPERIMENTAL

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

> 14 weeks of vedolizumab therapy + 15 mg vedolizumab-800CW group

EXPERIMENTAL

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

Interventions

Fluorescence molecular imaging procedure using vedolizumab-800CW DRUG

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.

15 mg vedolizumab-800CW group; 4.5 mg vedolizumab-800CW group

Fluorescence molecular imaging procedure without prior administration of vedolizumab-800CW OTHER

Fluorescence molecular imaging was performed to enable the visualization and detection of fluorescence signals.

Also known as: Control group

No administration of vedolizumab-800CW

Fluorescence molecular imaging procedure using vedolizumab-800CW with prior administration of unlabeled vedolizumab COMBINATION_PRODUCT

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.

300mg vedolizumab + 15mg vedolizumab-800CW group; 75 mg vedolizumab + 15 mg vedolizumab-800CW group; > 14 weeks of vedolizumab therapy + 15 mg vedolizumab-800CW group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Prior vedolizumab treatment
• Vedolizumab contraindicated as therapy
• Pregnancy or breast feeding.
• Patients younger than 18 years old

Sponsors & Collaborators

• University Medical Center Groningen: lead

Study Sites (1)

University Medical Center Groningen

Groningen, 9713 GZ, Netherlands

Location

Related Publications (3)

• 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.

  PMID: 31533965 BACKGROUND

• 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.

  PMID: 29247063 BACKGROUND

• Gabriels RY, van der Waaij AM, Linssen MD, Dobosz M, Volkmer P, Jalal S, Robinson D, Hermoso MA, Lub-de Hooge MN, Festen EAM, Kats-Ugurlu G, Dijkstra G, Nagengast WB. Fluorescently labelled vedolizumab to visualise drug distribution and mucosal target cells in inflammatory bowel disease. Gut. 2024 Aug 8;73(9):1454-1463. doi: 10.1136/gutjnl-2023-331696.

  PMID: 38580386 DERIVED

MeSH Terms

Conditions

Crohn Disease; Colitis, Ulcerative

Interventions

Control Groups

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Colitis; Colonic Diseases

Intervention Hierarchy (Ancestors)

Epidemiologic Research Design; Epidemiologic Methods; Investigative Techniques; Research Design; Methods

Study Officials

• W.B. Nagengast, MD, PhD, PharmD

  University Medical Center Groningen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: September 25, 2019
• First Posted: October 2, 2019
• Study Start: November 4, 2020
• Primary Completion: October 1, 2022
• Study Completion: January 1, 2023
• Last Updated: April 16, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)