Fluorescence Imaging of Adalimumab-680LT in Inflammatory Bowel Disease

Phase 2RecruitingNCT06117423

University Medical Center Groningen21 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

OTHER

Masking

NONE

Enrollment

Conditions

Crohn Disease Ulcerative Colitis

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Determine the safety of adalimumab-680LT in IBD

Evaluating possible (severe) adverse events (SAE \& AEs)

Time frame: Until 24 hours after administration

Blood pressure

Millimeters of mercure (mmHg)

Time frame: Five minutes before, and five and sixty minutes after tracer administration

Heart rate

Beats per minute

Time frame: Five minutes before, and five and sixty minutes after tracer administration

Temperature

Degrees Celsius

Time frame: Five minutes before, and five and sixty minutes after tracer administration

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.

Time frame: 12 months

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.

Time frame: 12 months

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

Time frame: 12 months

Secondary Outcomes

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

Time frame: 12 months

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

Time frame: 12 months

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?

Time frame: 12 months

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

Time frame: 12 months

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

Fluorescence Imaging of Adalimumab-680LT in Inflammatory Bowel Disease

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts