Crohn DiseasePhase 1VISIONNCT04112212
Using Vedolizumab-800CW to Gain Insight Into Local Drug Distribution and Mucosal Target Cells in IBD Patients
A Phase 1 study testing Fluorescence molecular imaging procedure using vedolizumab-800CW, Fluorescence molecular imaging procedure without prior administration of vedolizumab-800CW and Fluorescence molecular imaging procedure using vedolizumab-800CW with prior administration of unlabeled vedolizumab in people with Crohn Disease and Colitis, Ulcerative, run by University Medical Center Groningen at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Crohn Disease, Colitis, Ulcerative
- What is being tested?
- Fluorescence molecular imaging procedure using vedolizumab-800CW, Fluorescence molecular imaging procedure without prior administration of vedolizumab-800CW and Fluorescence molecular imaging procedure using vedolizumab-800CW with prior administration of unlabeled vedolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 1 siteNetherlands
- Study dates
- 4 Nov 2020to 1 Jan 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- Prior vedolizumab treatment
- Vedolizumab contraindicated as therapy
- Pregnancy or breast feeding.
- Patients younger than 18 years old
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Using Fluorescently Labeled Vedolizumab to Visualize Local Drug Distribution During Colonoscopy and Identify Mucosal Target Cells in Patients With Inflammatory Bowel Disease
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
- Being tested
- Fluorescence molecular imaging procedure using vedolizumab-800CW, Fluorescence molecular imaging procedure without prior administration of vedolizumab-800CW, Fluorescence molecular imaging procedure using vedolizumab-800CW with prior administration of unlabeled vedolizumab
- Keywords
- Fluorescence, Endoscopy, Vedolizumab-800CW
- Medical subject headings
- Crohn Disease, Colitis, Ulcerative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fluorescence molecular imaging procedure using vedolizumab-800CWDrug
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.
Fluorescence molecular imaging procedure without prior administration of vedolizumab-800CWOther
Also called Control group
Fluorescence molecular imaging was performed to enable the visualization and detection of fluorescence signals.
Fluorescence molecular imaging procedure using vedolizumab-800CW with prior administration of unlabeled vedolizumabCombination 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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: Combination Product: Fluorescence molecular imaging procedure using vedolizumab-800CW with prior administration of unlabeled vedolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: After 18 months when study is completed.
Secondary outcomes (4)
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.
Measured: 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
Measured: 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).
Measured: After 18 months when study is completed.
Distribution of Vedolizumab in the inflamed gut
To assess the (sub-)cellular location of vedolizumab-800CW microscopically.
Measured: After 18 months when study is completed.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Oct 2019
- Study start4 Nov 2020
- Primary completion1 Oct 2022
- Study completion1 Jan 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Crohn DiseaseStudies of the same condition, open and under way.
- More trials run by University Medical Center GroningenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Sequential
- 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
- Masking
- None (open label)
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Medical Center Groningen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- W.B. Nagengast, MD, PhD, PharmD, Principal investigator, University Medical Center Groningen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04112212
- Sponsor's protocol ID
- NL69572.042.19
- Acronym
- VISION
- Status last verified
- Apr 2024
- First submitted
- 25 Sep 2019
- Last updated
- 16 Apr 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 31533965Nagengast 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.
PubMed 29247063Gabriels 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.
PubMed 38580386
Study at a glance
From the registry record, last updated by the sponsor on 16 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Using Fluorescently Labeled Vedolizumab to Visualize Local Drug Distribution During Colonoscopy and Identify Mucosal Target Cells in Patients With Inflammatory Bowel Disease
- ClinicalTrials.gov ID
- NCT04112212
- Acronym / sponsor ID
- VISION / NL69572.042.19
- Conditions
- Crohn Disease, Colitis, Ulcerative
- Keywords
- Fluorescence, Endoscopy, Vedolizumab-800CW
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- University Medical Center GroningenUniversity, hospital or other
- Study start
- 4 Nov 2020 (actual)
- Primary completion
- 1 Oct 2022 (actual)
- Study completion
- 1 Jan 2023 (actual)
- First posted
- 2 Oct 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 6
- 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
| Arm | Type | Receives |
|---|---|---|
| No administration of vedolizumab-800CW | Other | Other: Fluorescence molecular imaging procedure without prior administration of vedolizumab-800CWPatients 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 |
| 4.5 mg vedolizumab-800CW group | Experimental | Drug: Fluorescence molecular imaging procedure using vedolizumab-800CWPatients received 4.5 mg vedolizumab-800CW and subsequently underwent a Fluorescence molecular imaging procedure |
| 15 mg vedolizumab-800CW group | Experimental | Drug: Fluorescence molecular imaging procedure using vedolizumab-800CWPatients received 15 mg vedolizumab-800CW and subsequently underwent a Fluorescence molecular imaging procedure |
| 75 mg vedolizumab + 15 mg vedolizumab-800CW group | Experimental | Combination Product: Fluorescence molecular imaging procedure using vedolizumab-800CW with prior administration of unlabeled vedolizumabPatients received 75mg vedolizumab + 15 mg vedolizumab-800CW and subsequently underwent a Fluorescence molecular imaging procedure |
| 300mg vedolizumab + 15mg vedolizumab-800CW group | Experimental | Combination Product: Fluorescence molecular imaging procedure using vedolizumab-800CW with prior administration of unlabeled vedolizumabPatients received 300mg vedolizumab + 15 mg vedolizumab-800CW and subsequently underwent a Fluorescence molecular imaging procedure |
| > 14 weeks of vedolizumab therapy + 15 mg vedolizumab-800CW group | Experimental | Combination Product: Fluorescence molecular imaging procedure using vedolizumab-800CW with prior administration of unlabeled vedolizumabPatients received 300mg vedolizumab + 15 mg vedolizumab-800CW after >14 weeks vedolizumab therapy and subsequently underwent a Fluorescence molecular imaging procedure |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (4 listed)
- Prior vedolizumab treatment
- Vedolizumab contraindicated as therapy
- Pregnancy or breast feeding.
- Patients younger than 18 years old
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Fluorescence molecular imaging procedure using vedolizumab-800CWFirst 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. | Drug | 15 mg vedolizumab-800CW group, 4.5 mg vedolizumab-800CW group |
| Fluorescence molecular imaging procedure without prior administration of vedolizumab-800CWAlso: Control groupFluorescence molecular imaging was performed to enable the visualization and detection of fluorescence signals. | Other | No administration of vedolizumab-800CW |
| Fluorescence molecular imaging procedure using vedolizumab-800CW with prior administration of unlabeled vedolizumabPatients 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. | Combination product | 300mg vedolizumab + 15mg vedolizumab-800CW group, 75 mg vedolizumab + 15 mg vedolizumab-800CW group, > 14 weeks of vedolizumab therapy + 15 mg vedolizumab-800CW group |
Primary outcome
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.
4 secondary outcomes
Safety of Vedolizumab-800CW in patients with IBD
Time frame: 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
Time frame: 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
Time frame: After 18 months when study is completed.
Distribution of Vedolizumab in the inflamed gut
Time frame: After 18 months when study is completed.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Apr 2024.
- Background: PubMed 31533965Tjalma 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.
- Background: PubMed 29247063Nagengast 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.
- Derived from this study: PubMed 38580386Gabriels 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
W.B. Nagengast, MD, PhD, PharmD principal investigator
University Medical Center Groningen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Fluorescence molecular imaging procedure using vedolizumab-800CW, Fluorescence molecular imaging procedure without prior administration of vedolizumab-800CW and Fluorescence molecular imaging procedure using vedolizumab-800CW with prior administration of unlabeled vedolizumab in people with Crohn Disease and Colitis, Ulcerative, run by University Medical Center Groningen at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Fluorescent signal in patients with IBD (time frame: After 18 months when study is completed.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04112212, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Apr 2024.