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

NCT07258641 | Not Yet Recruiting Phase 1

• 2 other identifiers: UMCG 217732025-521420-30-00
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Ulcerative Colitis (UC); Crohn Disease (CD)

Keywords

Fluorescence Molecular Endoscopy; Inflammatory Bowel Disease; Risankizumab-800CW; Adalimumab-680LT

Outcome Measures

Primary Outcomes (5)

• 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.

  12 months

• 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.

  12 months

• Blood pressure

  Systolic and diastolic in millimeters of mercure (mmHg)

  Five minutes before, and five and sixty minutes after tracer administration

• Heart rate

  Beats per minute

  Five minutes before, and five and sixty minutes after tracer administration

• Temperature

  Degrees Celsius

  Five minutes before, and five and sixty minutes after tracer administration

Secondary Outcomes (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.

  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.

  12 months

• To evaluate the adalimumab-680LT and risankizumab-800CW distribution inside mucosal biopsies

  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

  12 months

Study Arms (4)

25 mg adalimumab-680LT and 15/25 mg risankizumab-800CW

EXPERIMENTAL

Patients receive 25 mg adalimumab-680LT and 15/25 mg risankizumab-800CW and undergo a Fluorescence Molecular Imaging Procedure

Drug: 25mg adalimumab-680LT and 15/25 mg risankizumab-800CW

25 mg adalimumab-680LT

EXPERIMENTAL

Patients starting with adalimumab will receive 25 mg adalimumab-680LT and undergo a Fluorescence Molecular Imaging procedure

Drug: Adalimumab-680LT 25mg

15/25 mg risankizumab-800CW

EXPERIMENTAL

Patients starting with risankizumab receive 15/25 mg risankizumab-800CW and undergo a Fluorescence Molecular Imaging procedure

Drug: Risankizumab-800CW 15 mg/25 mg

No second procedure

NO INTERVENTION

Patients starting with drugs other than adalimumab or risankizumab will not undergo a second procedure

Interventions

25mg adalimumab-680LT and 15/25 mg risankizumab-800CW DRUG

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.

25 mg adalimumab-680LT and 15/25 mg risankizumab-800CW

Adalimumab-680LT 25mg DRUG

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.

25 mg adalimumab-680LT

Risankizumab-800CW 15 mg/25 mg DRUG

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.

15/25 mg risankizumab-800CW

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• University Medical Center Groningen: lead

Study Sites (1)

University Medical Center Groningen

Groningen, Provincie Groningen, 9713GZ, Netherlands

Location

MeSH Terms

Conditions

Colitis, Ulcerative; Crohn Disease; Inflammatory Bowel Diseases

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Colonic Diseases; Intestinal Diseases

Central Study Contacts

Wouter B Nagengast, MD, PharmD, PhD, Professor

CONTACT

+31(0)503612620; w.b.nagengast@umcg.nl

Antonio M da Costa de Pina, MSc

CONTACT

+31(0)625648290; a.m.da.costa.de.pina@umcg.nl

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2025
• First Posted: December 2, 2025
• Study Start: January 15, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): April 1, 2028
• Last Updated: January 14, 2026

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)