Fluorescence Imaging of Adalimumab-680LT in Inflammatory Bowel Disease

Ulcerative Colitis Clinical Trial

— GUIDE  

Official title:

Investigating the Safety, Feasibility, and Optimal Dose of Fluorescently Labeled Adalimumab-680LT for Visualizing Drug Targeting in Inflammatory Bowel Diseases

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06117423
• Other study ID #: 18146
• Secondary ID: 2023-508391-11-0
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: March 2024
• Est. completion date: June 2025

Study information

• Verified date: March 2024
• Source: University Medical Center Groningen
• Contact: Wouter B Nagengast, MD, PhD, PharmD
• Phone: +31(0)503612620
• Email: w.b.nagengast[@]umcg.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Crohn's Disease (CD) and Ulcerative Colitis (UC) are chronic inflammatory bowel diseases (IBD). Adalimumab is a human monoclonal antibody against TNF-alpha, a pro-inflammatory cytokine that mediates the inflammatory response in IBD upon binding to the TNF receptors. Primary non-response to adalimumab is high in both CD and UC. Currently, there are no predictors of response to adalimumab and the actual mechanism of action has not yet been elucidated. To gain better understanding of the drug targeting of adalimumab in IBD, the University Medical Center Groningen (UMCG) developed fluorescently labeled adalimumab (adalimumab-680LT). This study aims to assess the safety and the optimal dose of adalimumab-680LT to visualize and potentially quantify the local drug concentration and predict treatment response in IBD patients using in vivo and ex vivo fluorescence molecular imaging (FMI).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 21
• Est. completion date: June 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Established IBD diagnosis (UC or CD)

• Active disease (clinically defined as at least mild activity using dedicated scoring indices and biochemically defined by a fecal calprotectin > 60 µg/g, measured within the last 6 weeks before inclusion)

• Patients must be eligible for adalimumab therapy

• Clinical indication for an endoscopic procedure

• Age: 18 years or older

• Written informed consent

• For female patients of premenopausal age with intact reproductive organs or who are less than 2 years postmenopausal, a negative pregnancy test must be available.

Exclusion Criteria:

• Pregnancy or breast feeding

• Female patient of premenopausal age who does not use any reliable form of contraception at the time of adalimumab-680LT administration and the following 10 weeks.

• Medical or psychiatric conditions that compromise the patient's ability to give informed consent

• Prior anti-TNF therapy in the last 6 weeks before inclusion

• Active extra gastrointestinal manifestations of Crohn's disease

• Previous treatment with adalimumab and detectable anti-adalimumab antibodies levels

Related Conditions & MeSH terms

• Crohn Disease
• Inflammatory Bowel Diseases
• Intestinal Diseases
• Ulcerative Colitis

Intervention

Drug:
• Adalimumab-680LT
First, adalimumab-680LT was administered intravenously. 2-3 days later, a Fluorescence Molecular Imaging procedure was performed to enable the visualisation and detection of fluorescence signals.

Other:
• Control
Fluorescence Molecular Imaging was performed to enable the visualisation and detection of fluorescence signals.

Locations

Country	Name	City	State
Netherlands	University Medical Center Groningen	Groningen

Sponsors (1)

Lead Sponsor	Collaborator
University Medical Center Groningen

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determine the safety of adalimumab-680LT in IBD	Evaluating possible (severe) adverse events (SAE & AEs)	Until 24 hours after administration
Primary	Blood pressure	Millimeters of mercure (mmHg)	Five minutes before, and five and sixty minutes after tracer administration
Primary	Heart rate	Beats per minute	Five minutes before, and five and sixty minutes after tracer administration
Primary	Temperature	Degrees Celsius	Five minutes before, and five and sixty minutes after tracer administration
Primary	Investigate the feasibility of using FME to detect adalimumab-680LT signals	Evaluating the performance of FME for detecting adalimumab-680LT signals. This evaluation will be based on a visual evaluation during FME (visible signal yes/no), TBR and CNR calculations and MDSFR/SFF measurements.	12 months
Primary	Investigate the feasibility of using ex vivo FMI to detect adalimumab-680LT	Evaluating the performance of ex vivo FMI for detecting adalimumab-680LT signals. This evaluation will be based on mean fluorescence intensities (MFIs) of biopsies and fluorescence/light sheet microscopy.	12 months
Primary	Determining the optimal imaging dose of adalimumab-680LT	The optimal dose will be based on the adalimumab-680LT signals during FME and ex vivo FMI	12 months
Secondary	Investigate a potential correlation of in vivo fluorescence signal intensities and target saturation to clinical response/remission after 14 weeks of adalimumab therapy regimen in patients with IBD	Evaluation of the potential correlation in vivo will be based on in vivo fluorescence images and the MDSFR/SFF measurements before and after at least 14 weeks of adalimumab treatment	12 months
Secondary	Investigate a potential correlation of ex vivo fluorescence signal intensities and target saturation to clinical response/remission after 14 weeks of adalimumab therapy regimen in patients with IBD	Evaluation of the potential correlation ex vivo will be based on MFIs of biopsies, fluorescence microscopy results, and tracer concentrations inside biopsies before and after at least 14 weeks of adalimumab treatment	12 months
Secondary	Quantify the fluorescence signals of the tracer in vivo by using single-fiber reflectance/single-fiber fluorescence (MDSFR/SFF) spectroscopy and correlate these measurements to tracer dose, in vivo fluorescence intensities and inflammation severity	Quantification of MDSFR/SFF measurements in inflamed tissue compared to measurements in non-inflamed tissue. Positive correlation between MDSFR/SFF measurements and dose/inflammation severity?	12 months
Secondary	To correlate ex vivo fluorescence signals to inflammation severity and tracer dose based on histopathological examination inside the obtained biopsies	Histologically ascertained tissue types (qualitative): Normal (non-inflamed) ileal, colon and rectal tissue Inflamed ileum, colon and rectum tissue Random ''high-fluorescent'' tissue Random ''Non-fluorescent'' tissue	12 months
Secondary	To assess tracer stability, tracer distribution and tracer concentration, and to identify the composition of immune cells ex vivo to learn more about adalimumab mucosal target cells	Fluorescence (confocal) microscopy with additional use of immune panels and spatial transcriptomics analysis (before and after at least 14 weeks of adalimumab treatment). Measurements of the adalimumab-680LT concentration by light-sheet microscopy after tissue clearing, insights in adalimumab-target cells and presence of immune cells inside the biopsies and blood samples by flow cytometry and assessment of tracer stability by Western Blot	12 months