Dual wavelength fluorescence imaging using fluorescently labelled adalimumab and risankizumab for visualizing drug targeting in Inflammatory Bowel Diseases (VOYAGER)

This feasibility study evaluates the capability of the Windu system to perform dual tracer **fluorescence molecular endoscopy** and ex vivo **fluorescence molecular imaging** for the detection of **adalimumab-680LT** and **risankizumab-800CW** signals in patients with **Inflammatory Bowel Disease**. The primary objective addresses the technical feasibility of simultaneous visualization of two fluorescently labeled **biologic therapies** targeting distinct inflammatory pathways, which is clinically relevant for understanding drug distribution and target engagement in intestinal mucosa.

The secondary objectives include:

• Investigation of potential correlations between in vivo and ex vivo **fluorescence signal intensities** and **target saturation** with clinical response and remission following 14 weeks of adalimumab or risankizumab therapy in patients with Inflammatory Bowel Disease

• Quantification of tracer fluorescence signals in vivo using **single-fiber reflectance/single-fiber fluorescence spectroscopy** and correlation of these measurements with **inflammation severity**

• Evaluation of adalimumab-680LT and risankizumab-800CW distribution within **mucosal biopsies**

• Identification of **immune cell composition** in the mucosal microenvironment of Inflammatory Bowel Disease patients to gain insights into target cells and distribution patterns of adalimumab and risankizumab

The sponsor did not provide information regarding the total number of participants enrolled in this clinical trial. The study population includes adult participants aged 18 years and older with an established diagnosis of **Inflammatory Bowel Disease (IBD)**, specifically **ulcerative colitis** or **Crohn's disease**. Both male and female subjects are eligible for enrollment. Participants must present with active disease, defined as clinically active bowel disease with at least mild activity according to dedicated scoring indices or biochemically active disease characterized by **fecal calprotectin** levels exceeding 60 μg/g. The trial population was selected based on eligibility for **adalimumab** or **risankizumab** therapy and a clinical indication for an endoscopic procedure. Female participants of childbearing potential are required to provide a negative pregnancy test. No vulnerable populations are included in this study.

This clinical trial investigates the feasibility of dual wavelength **fluorescence molecular endoscopy** using fluorescently labeled **adalimumab** and **risankizumab** for visualizing drug targeting in patients with **Inflammatory Bowel Disease**. The study employs a Phase I/II intervention design to evaluate the Windu system's capability to detect adalimumab-680LT and risankizumab-800CW signals through **in vivo** fluorescence molecular endoscopy and **ex vivo** fluorescence microscopy imaging. The investigational medicinal products consist of Skyrizi 600 mg concentrate for **solution for infusion** containing risankizumab conjugated with IRDye 800CW administered via **intravenous administration**, and Humira 40 mg **solution for injection** in pre-filled syringe containing adalimumab labeled with IRDye 680LT administered via **subcutaneous** route.

The primary endpoint focuses on visual evaluation and distinction of both tracers during fluorescence molecular endoscopy, including assessment of visible signal presence, **target-to-background ratio** and **contrast-to-noise ratio** calculations, mean fluorescence intensities of biopsies, multidiameter single fiber reflectance and single fiber fluorescence measurements, and fluorescence/light sheet microscopy analysis. Secondary endpoints include analysis of in vivo fluorescence images with real-time quantification of fluorescence signal by **spectroscopy**, semi-quantification of fluorescence within mucosal biopsies using fluorescence scans compared with endoscopic and histologic inflammation scores, and correlation analysis between measured fluorescence and clinical response to therapy. Additional secondary objectives involve quantification of fluorescent signals by dual wavelengths spectroscopy during endoscopy correlated with inflammation severity, three-dimensional ex vivo fluorescence signal analysis on intact biopsies, **SDS-PAGE** analysis with protein extract to prove tracer integrity, detection of **TNF** and **IL23** protein and mRNA expression via **Western Blot**, and fluorescence microscopy on **FFPE** slides with immunofluorescence staining for immune cell markers including CD68, CD3, CD8, and CD20 to identify cell types positive for the labeled antibodies.

Eligible participants include adults aged 18 years or older with an established diagnosis of **ulcerative colitis** or **Crohn's disease** who present with active disease defined as clinically active bowel disease with at least mild activity using dedicated scoring indices or biochemically active disease with **fecal calprotectin** exceeding 60 μg/g. Participants must be eligible for adalimumab or risankizumab therapy and have a clinical indication for an endoscopic procedure. Female subjects of childbearing potential must provide a negative pregnancy test. All participants must provide written **informed consent** prior to enrollment.

The study is scheduled to commence recruitment in January 2026 with an estimated completion date of March 2027, resulting in an overall trial duration of approximately 15 months. Participant involvement includes a screening visit to assess eligibility criteria, followed by administration of the fluorescently labeled investigational products and subsequent endoscopic evaluation with fluorescence molecular endoscopy. During the endoscopic procedure, mucosal biopsies will be obtained from areas demonstrating high and low fluorescence signals for ex vivo analysis. Blood samples will be collected for tracer integrity assessment and correlation studies. The end-of-study visit will complete the participant's involvement in the trial. Early termination from the study may occur due to withdrawal of consent, adverse events requiring discontinuation, protocol violations, or investigator decision based on safety concerns or participant's best interest.

The experimental treatment consists of two fluorescently labelled **monoclonal antibodies** used for dual wavelength **fluorescence imaging** in patients with **Inflammatory Bowel Diseases**. Both investigational medicinal products represent modifications of authorized biologics through conjugation with fluorescent dyes for visualization purposes during **fluorescence molecular endoscopy** and ex vivo fluorescence molecular imaging.

**Risankizumab-800CW** is administered as a **solution for infusion** derived from Skyrizi 600 mg concentrate for solution for infusion. The active substance **risankizumab** is conjugated with **IRDye 800CW** fluorescent marker. The product is administered via **intravenous administration**. Risankizumab is a protein-based therapeutic agent with synonyms including BI 655066, ABBV-066, and CKD-704. The conjugation with IRDye 800CW represents a modification from the marketed authorization to enable fluorescence detection during endoscopic procedures.

**Adalimumab-680LT** is administered as a **solution for injection** derived from Humira 40 mg solution for injection in pre-filled syringe. The active substance **adalimumab** is labelled with **IRDye 680LT** fluorescent marker. The product is administered via **subcutaneous** route. Adalimumab is a protein-based therapeutic agent with synonyms including ABP 501, BI 695501, and MSB11022. The labelling with IRDye 680LT represents a modification from the marketed authorization to enable dual tracer fluorescence detection using the Windu system.

The dual wavelength approach allows simultaneous detection of both fluorescently labelled antibodies during endoscopic examination. The Windu system is utilized for visualization and detection of fluorescence signals from both tracers. Participant compliance monitoring and drug administration procedures follow protocols designed to ensure adequate fluorescence signal detection during both in vivo endoscopic imaging and ex vivo tissue imaging procedures.

Efficacy will be assessed through multiple parameters evaluating the feasibility and performance of dual tracer **fluorescence molecular endoscopy** and ex vivo fluorescence molecular imaging. The primary endpoint includes visual evaluation and distinction of both tracers during fluorescence molecular endoscopy, determination of tracer visibility, target-to-background ratio and contrast-to-noise ratio calculations, mean fluorescence intensities of biopsies, multispectral diffuse scanning fluorescence reflectance and single fiber fluorescence measurements, and fluorescence/light sheet microscopy.

Secondary endpoints encompass analysis of in vivo fluorescence images with real-time quantification of fluorescence signal by spectroscopy. Semi-quantification of fluorescence within mucosal biopsies will be performed using fluorescence scans and compared with endoscopic and histologic inflammation scores as well as in vivo results. Correlation between in vivo and ex vivo measured fluorescence and endoscopic/histologic response to **adalimumab** and **risankizumab** therapy will be evaluated. Quantification of fluorescent signals by dual wavelengths spectroscopy during endoscopy will be correlated with fluorescence intensities visualized using the fluorescence molecular endoscopy camera and endoscopic/histologic inflammation severity to assess drug distribution into inflamed or non-inflamed tissue. Three-dimensional ex vivo fluorescence signal analysis will be conducted on intact biopsies taken from high and low fluorescence areas to assess the distribution of labeled **adalimumab-680LT** and **risankizumab-800CW**. Tracer integrity will be verified using SDS-PAGE with protein extract from biopsies and blood samples. Protein and mRNA expression of **TNF** and **IL23** will be detected via Western Blot to determine correlation between tracer signal and target expression. Fluorescence microscopy on formalin-fixed paraffin-embedded slides will be performed to microscopically visualize the tracer signals, with additional immunofluorescence staining for different immune cell markers including CD68, CD3, CD8, and CD20 to identify the immune cell types of tracer-positive cells.