Fluorescence Imaging of Adalimumab-680LT and Risankizumab-800CW in Inflammatory Bowel Disease

Official title

Dual Wavelength Fluorescence Imaging Using Fluorescently Labelled Adalimumab and Risankizumab for Visualizing Drug Targeting in Inflammatory Bowel Diseases

Overview

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.

Interventions

• Drug 25mg adalimumab-680LT and 15/25 mg risankizumab-800CW
  Adalimumab-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.
• Drug Adalimumab-680LT 25mg
  Adalimumab-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.
• Drug Risankizumab-800CW 15 mg/25 mg
  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 fluorescence signals.

Primary outcome measures

• To investigate the feasibility of using dual wavelengths fluorescence molecular endoscopy (FME) [Time frame: 12 months]
• To investigate the feasibility of using ex vivo fluorescence molecular imaging (FMI) to detect adalimumab-680LT and risankizumab-800CW signals [Time frame: 12 months]
• Blood pressure [Time frame: Five minutes before, and five and sixty minutes after tracer administration]
• Heart rate [Time frame: Five minutes before, and five and sixty minutes after tracer administration]
• Temperature [Time frame: Five minutes before, and five and sixty minutes after tracer administration]

Secondary outcome measures (4)

• 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. [Time frame: 12 months]
• 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. [Time frame: 12 months]
• To evaluate the adalimumab-680LT and risankizumab-800CW distribution inside mucosal biopsies [Time frame: 12 months]
• 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 [Time frame: 12 months]

Eligibility criteria

Inclusion criteria

Patients eligible for inclusion meet all of the following criteria:

• 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
• Written informed consent
• Clinical indication for an endoscopic procedure

For female subjects who are of childbearing potential, are premenopausal with intact reproductive organs, or are less than 2 years postmenopausal:

• A negative pregnancy test (urine or blood test) must be available.

Exclusion criteria

A female study patient who is pregnant or provides breastfeeding

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Other

Study locations

Netherlands · 1 center

• University Medical Center Groningen — Groningen

Identifiers

NCT: NCT07258641 · UMCG 21773 · 2025-521420-30-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗