Fluorescence Imaging of Adalimumab-680LT and Risankizumab-800CW in Inflammatory Bowel Disease
Trial statusNot yet recruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity Medical Center Groningen
About this trial
Inflammatory bowel diseases (IBD) are chronic relapsing inflammatory disorders of the gastrointestinal tract affecting 2.5 million patients in Europe alone. The majority of newly diagnosed patients are in adolescence or early adulthood and in the midst of their family life, career, and social development.
IBD comes with significant morbidity and complex treatment strategies and is associated with a high social burden and medical costs. Besides other factors, the pathogenesis of IBD is attributed to proinflammatory cytokine tumor necrosis factor α (TNFα) and Interleukin 23 (IL-23). Adalimumab, a human monoclonal anti-TNF antibody, and risankizumab, a humanized monoclonal anti-IL-23 antibody, are used to treat patients with moderate to severely active IBD. However, IBD patients often only partially respond to such biological immunomodulating therapies, resulting in high primary nonresponse (30-60%) and loss of response over time (48-58%). The investigators are currently missing reliable tools for response prediction because the limitations of current technologies do not allow the visualization of the molecular phenotype or heterogeneity within patients. Therefore, patients are potentially exposed to a non-effective treatment and its potential side effects while clinical deterioration is ongoing. In addition, it remains completely unknown for most biologicals used for IBD therapy whether they reach their actual targets in the tissue and if a sufficient local concentration is present to achieve treatment response. To develop a predictive tool for assessment of therapeutic (non-)response to patients and gain insights into local drug concentrations in individual patients before initiating anti-TNF or anti-IL23 therapy, the University Medical Center Groningen (UMCG), fluorescently labeled adalimumab (adalimumab-680LT) and risankizumab (risankizumab-800CW) to visualize and quantify the labeled drugs in diseased tissue with dedicated optical fluorescence imaging systems. In previous studies, the investigators have proven that those tracers bind to TNFα/IL23 in the mucosa after intravenous injection and that the investigators can investigate the drug distribution in vivo due to the colocalization of the fluorescently labeled compound. The aim of this follow-up study is to assess the feasibility of simultaneous dual wavelength imaging of adalimumab-680LT and risankizumab-800CW at baseline and evaluate target saturation after at least 14 weeks of adalimumab or risankizumab therapy. The investigators will also use in vivo and ex vivo fluorescence molecular imaging (FMI) to visualize tracer target cells and the patient's molecular phenotype for potential treatment response prediction in IBD patients in the future.
The investigators will determine the feasibility of dual wavelengths molecular fluorescence imaging using the GMPproduced near-infrared fluorescent tracers adalimumab-680LT and risankizumab-800CW for visualizing medicine distribution in and ex vivo IBD patients with dedicated fluorescence imaging systems.
Furthermore, the investigators will evaluate TNF and IL23 target saturation after 14 weeks of adalimumab or risankizumab therapy and characterize the tissue microenvironment where the drug is abundant and identify potential drug target cells.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Established IBD diagnosis (UC or CD).
Active disease: clinically active disease of the bowel is defined as at least mild activity using dedicated scoring indices or biochemically active disease as defined by a fecal calprotectin > 60 µg/g
Patients must be eligible for adalimumab or risankizumab therapy.
Age of 18 years
Disqualifiers
A female study patient of premenopausal age who does not use any reliable form of contraception at the time of adalimumab-680LT and/or risankizumab 800CW administration
Medical or psychiatric conditions that compromise the patient's ability to give informed consent
Prior anti-IL23-specific therapy (IL23/IL12 combination therapy is not an exclusion criteria)
Prior anti-TNFα therapy in the last 6 weeks before inclusion
Trial design
Design model
Sequential
Treatments tested in this trial
25mg adalimumab-680LT and 15/25 mg risankizumab-800CW
DrugAdalimumab-680LT and risankizumab-800CW will be administered intravenously. 2-3 days later, a Fluorescence Molecular Imaging procedure will be performed to enable the visualisation and detection of dual-wavelength fluorescence signals.
Adalimumab-680LT 25mg
DrugAdalimumab-680LT will be administered intravenously. 2-3 days later, a Fluorescence Molecular Imaging procedure will be performed to enable the visualisation and detection of fluorescence signals.
Risankizumab-800CW 15 mg/25 mg
DrugRisankizumab-800CW will be administered intravenously. 2-3 days later, a Fluorescence Molecular Imaging procedure will be performed to enable the visualisation and detection of fluorescence signals.
Treatment groups
30 Participants
are divided into 4 treatment groupsGroup A: 25 mg adalimumab-680LT and 15/25 mg risankizumab-800CWExperimental treatment 1 intervention
Group B: 25 mg adalimumab-680LTExperimental treatment 1 intervention
Group C: 15/25 mg risankizumab-800CWExperimental treatment 1 intervention
Group D: No second procedureNo intervention 0 interventions
Trial outcomes
Primary outcomes
1
To investigate the feasibility of using dual wavelengths fluorescence molecular endoscopy (FME)
Visual evaluation and distinction of both tracers during FME (visible signal yes/no), as well as TBR and CNR calculations, will be performed to assess in vivo signal detectability.
Time frame
12 months2
To investigate the feasibility of using ex vivo fluorescence molecular imaging (FMI) to detect adalimumab-680LT and risankizumab-800CW signals
Ex vivo analysis will include mean fluorescence intensities (MFIs) of biopsies, MDSFR/SFF measurements, and fluorescence and light sheet microscopy to quantify and localize tracer signals.
Time frame
12 months3
Blood pressure
Systolic and diastolic in millimeters of mercure (mmHg)
Time frame
Five minutes before, and five and sixty minutes after tracer administration4
Heart rate
Beats per minute
Time frame
Five minutes before, and five and sixty minutes after tracer administrationSecondary outcomes
1
To investigate a potential correlation of in vivo and ex vivo fluorescence signal intensities and target saturation to clinical response/remission after 14 weeks of adalimumab/risankizumab therapy regimen in patients with IBD.
This will involve semi-quantitative and spectroscopic analysis of fluorescence signals during endoscopy and in biopsies, comparison with inflammation scores, and molecular validation of tracer binding and immune cell localization to assess predictive and response-related biomarkers.
Time frame
12 months2
To quantify the fluorescence signals of the tracers in vivo by using single-fiber reflectance/single-fiber fluorescence (MDSFR/SFF) spectroscopy and correlate these measurements to inflammation severity.
This will be achieved through real-time spectroscopic quantification of fluorescence signals during endoscopy in each investigated bowel segment, followed by comparison with endoscopic and histologic inflammation scores to assess the relationship between tracer signal intensity and tissue inflammation.
Time frame
12 months3
To evaluate the adalimumab-680LT and risankizumab-800CW distribution inside mucosal biopsies
This will be achieved through 3D ex vivo fluorescence signal analysis of intact biopsies collected from high and low fluorescence areas during endoscopy, enabling assessment of tracer distribution across inflamed and non-inflamed tissue. Additional validation will include SDS-PAGE to confirm tracer integrity, fluorescence microscopy, and immunofluorescence staining to visualize and quantify tracer-positive cells and their immune cell types.
Time frame
12 months4
To identify the composition of immune cells in the mucosal microenvironment of IBD patients and gain new insights into the target cells and distribution of adalimumab and risankizumab
This will be addressed through fluorescence microscopy and immunofluorescence staining of FFPE biopsy slides to visualize adalimumab-680LT and risankizumab-800CW signals and identify immune cell types (e.g., CD68, CD3, CD8, CD20). The number and distribution of tracer-positive cells and immune subsets will be quantified to explore associations with therapy response and mucosal immune profiles.
Time frame
12 monthsSponsors and contacts
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Source ClinicalTrials.gov
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