Fluorescence Imaging of IBD and RA Using Adalimumab-800CW

Official title

Near-infrared Fluorescence Molecular Imaging of Adalimumab-800CW to Elucidate the Drug Distribution Throughout Inflamed Tissue in Inflammatory Bowel Disease and Rheumotoid Arthritis

Overview

Inflammatory bowel disease (IBD) and rheumatoid arthritis (RA) are both auto-immune diseases that are characterized by chronic relapsing inflammation of respectively the ileocolonic tissue and the synovium. Pathogenesis of both auto-immune diseases is attributed to the proinflammatory cytokine tumor necrosis factor α (TNFa). Adalimumab is a human monoclonal anti-TNF antibody used for treating patients with moderate to severely active IBD and RA. However, current rates of therapeutic nonresponsiveness to this antibody are variable and difficult to predict in advance, whereas patients are potentially exposed to a non-effective treatment and its potential side effects; while clinical deterioration progresses. A key unmet need is the development of a predictive tool for assessment of a therapeutic (non-) response to patients and finding an optimal dose strategy in individual patients before initiating anti-TNF therapy. Unfortunately, we currently lack crucial information about drug distribution of the drug of interest throughout the targeted inflamed tissue itself. Therefore, it remains unknown in both IBD and RA, if the drug reaches its target (in sufficient amounts) and how local drug concentrations are related to therapeutic response. Thus, we linked adalimumab to a fluorescent dye (adalimumab-800CW) in order to create a fluorescent signal of the labelled drug in the diseased tissue that we can visualize and quantify with dedicated optical fluorescence imaging systems. We hypothesize that this tracer will bind to TNFa in the mucosa/synovium and thus create a map of medicine distribution in vivo due to colocalization of the fluorescent labelled compound. Therefore, the aim of this study is to assess the feasibility of fluorescent molecular imaging of adalimumab-800CW in IBD and RA patients.

Detailed description

See brief summary

Interventions

• Drug Adalimumab-800CW
  Intravenous administration of 4.5 mg, 15 mg or 25 mg 2 - 4 days prior to the fluorescence imaging
• Device Fluorescence Imaging
  Rheumatoid arthritis: a flexible fiber-bundle is attached to a fluorescence camera platform to enable the detection of fluorescence signals open-air by using a black-box. Inflammatory bowel disease: a flexible fiber-bundle is attached to a fluorescence camera platform to enable the detection of fluorescence signals. The fluorescence fibre-probe is inserted through the standard working channel of the standard clinical endoscope. Fluorescence imaging will be performed during standard clinical col

Primary outcome measures

• Safety: number of participants with symptoms or changes in vital signs (blood pressure, heart rate and temperature) that are related to administration of adalimumab-800CW [Time frame: Up to 30 minutes after stop tracer injection]
• Safety: number of participants with (serious) adverse events that are related to the administration of adalimumab-800CW [Time frame: Up to 24 hours after tracer injection]
• Discrimination of inflamed and normal tissue based on in vivo fluorescence measurements from adalimumab-800CW gained during fluorescence imaging of the hand of rheumatoid arthritis patients [Time frame: Up to 1 year]
• Discrimination of inflamed and normal tissue based on in vivo and ex vivo fluorescence measurements from adalimumab-800CW gained during fluorescence endoscopy in patients with ulcerative colitis (UC). [Time frame: Up to 1 year]
• Discrimination of inflamed and normal tissue based on in vivo and ex vivo fluorescence measurements from adalimumab-800CW gained during fluorescence endoscopy in patients with Crohn's disease (CD). [Time frame: Up to 1 year]

Secondary outcome measures (9)

• The correlation between the fluorescence intensity and the disease activity measured with the DAS28 in patients with RA. [Time frame: Up to 1 year]
• Calculation of optical properties with MDSFR/SFF spectroscopy in patients with RA [Time frame: Up to 1 year]
• The correlation between fluorescence intensity and the clinical disease activity score in ulcerative colitis using the SCCAI; [Time frame: Up to 1 year]
• The correlation between fluorescence intensity and the endoscopic disease activity score in ulcerative colitis using the Mayo endoscopic subscore; [Time frame: Up to 1 year]
• The correlation between fluorescence intensity and the clinical disease activity score in Crohn's disease using the Crohn's Disease Activity Index (CDAI). [Time frame: Up to 1 year]
• The correlation between fluorescence intensity and the disease activity score in Crohn's disease using the SES-CD score [Time frame: Up to 1 year]
• The correlation and validation of fluorescence signals detected in vivo to the pathology of biopsies for IBD patients; [Time frame: Up to 1 year]
• Quantification of fluorescence signals in vivo and ex vivo of inflamed and normal tissue using multi-diameter single-fiber reflectance, single-fiber fluorescence (MDSFR/SFF) spectroscopy measurements in IBD patients; [Time frame: Up to 1 year]
• Correlation in IBD between the detected fluorescence signals in vivo and the clinical response to induction therapy at week 14. [Time frame: Up to 1 year]

Eligibility criteria

Inclusion criteria

• Established IBD or RD diagnosis
• Active disease.

• IBD cohort: clinically active disease of the bowel defined either clinically as at least mild activity using dedicated scoring indices (for definitions of disease activity, see below) or biochemically active disease as defined by a faecal calprotectin > 200 µg/g;
• RA cohort: clinically active disease of at least one joint of the hand as assessed by a rheumatologist;
• Age of 18 years or older and mentally competent;
• Written informed consent.

IBD patients must already have an ileocolonoscopy scheduled due to a clinical indication.

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

• A negative pregnancy test must be available
• Willing to ensure that she uses effective contraception during the study and for 3 months thereafter.

Exclusion criteria

• Medical or psychiatric conditions that compromise the patient's ability to give informed consent;
• A potential female subject that is pregnant or provides breastfeeding will be excluded from participation in this study.
• The exclusion criterium that is specific for RD patients involves a skin type above type 3 according to the Fitzpatrick scale due to feasibility of the MDSFR/SFF spectroscopy measurements.

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

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Netherlands · 1 center

• University Medical Center Groningen — Groningen

Publications

• Gabriels RY, van der Waaij AM, Linssen MD, Dobosz M, Volkmer P, Jalal S, Robinson D, Hermoso MA, Lub-de Hooge MN, Festen EAM, Kats-Ugurlu G, Dijkstra G, Nagengast WB. Fluorescently labelled vedolizumab to visualise drug distribution and mucosal target cells in inflammatory bowel disease. Gut. 2024 Aug 8;73(9):1454-1463. doi: 10.1136/gutjnl-2023-331696. PMID 38580386

Identifiers

NCT: NCT03938701 · NL75246.042.20

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗