Fluorescence Imaging of IBD and RA Using Adalimumab-800CW

NCT03938701 | Recruiting Phase 2

• 1 other identifier: NL75246.042.20
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

IBD; Rheumatoid Arthritis

Keywords

Molecular imaging; Adalimumab-800CW; Fluorescence; Inflammatory bowel disease; Rheumatoid arthritis

Outcome Measures

Primary Outcomes (5)

• 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

  To determine the safety of adalimumab-800CW in inflammatory bowel disease (IBD) and rheumatoid arthritis patients by monitoring of vital signs (blood pressure, heart rate and temperature) before, during and after tracer infusion. These vital signs are measured before tracer administration, directly after and then every 15 minutes until 1 hour after tracer administration.

  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

  (serious) adverse events will be monitored until 24 hours after tracer administration.

  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

  The target-to-background/contrast-to-noise ratio will be calculated after fluorescence imaging. These results will be related to the gold standard clinical care to evaluate the feasibility of molecular fluorescence imaging using the tracer adalimumab-800CW for the evaluation of drug distribution in patients with rheumatoid arthritis.

  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).

  The target-to-background/contrast-to-noise ratio will be calculated after fluorescence molecular endoscopy (FME) and MDSFR/SFF spectroscopy. These results will be related to the gold standard clinical care to evaluate the feasibility of fluorescence molecular endoscopy using the tracer adalimumab-800CW for the evaluation of drug distribution in patients with ulcerative colitis.

  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).

  The target-to-background/contrast-to-noise ratio will be calculated after fluorescence molecular endoscopy (FME) and MDSFR/SFF spectroscopy. These results will be related to the gold standard clinical care to evaluate the feasibility of fluorescence molecular endoscopy using the tracer adalimumab-800CW for the evaluation of drug distribution in patients with Crohn's disease.

  Up to 1 year

Secondary Outcomes (9)

• The correlation between the fluorescence intensity and the disease activity measured with the DAS28 in patients with RA.

  Up to 1 year

• Calculation of optical properties with MDSFR/SFF spectroscopy in patients with RA

  Up to 1 year

• The correlation between fluorescence intensity and the clinical disease activity score in ulcerative colitis using the SCCAI;

  Up to 1 year

• The correlation between fluorescence intensity and the endoscopic disease activity score in ulcerative colitis using the Mayo endoscopic subscore;

  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).

  Up to 1 year

Study Arms (4)

1. Fluorescence imaging of inflammatory bowel disease and rheumatoid arthritis with adalimumab-800CW

EXPERIMENTAL

Fluorescence imaging with 4.5 mg adalimumab-800CW in inflammatory bowel disease and rheumatoid arthritis.

Drug: Adalimumab-800CW; Device: Fluorescence Imaging

2. Fluorescence imaging of inflammatory bowel disease and rheumatoid arthritis with adalimumab-800CW

EXPERIMENTAL

Fluorescence imaging with 15 mg adalimumab-800CW in inflammatory bowel disease and rheumatoid arthritis.

Drug: Adalimumab-800CW; Device: Fluorescence Imaging

3. Fluorescence imaging of inflammatory bowel disease and rheumatoid arthritis with adalimumab-800CW

EXPERIMENTAL

Fluorescence imaging with 25 mg adalimumab-800CW in inflammatory bowel disease and rheumatoid arthritis.

Drug: Adalimumab-800CW; Device: Fluorescence Imaging

4. Fluorescence imaging of inflammatory bowel disease and rheumatoid arthritis

EXPERIMENTAL

Fluorescence imaging without adalimumab-800CW in inflammatory bowel disease and rheumatoid arthritis.

Device: Fluorescence Imaging

Interventions

Adalimumab-800CW DRUG

Intravenous administration of 4.5 mg, 15 mg or 25 mg 2 - 4 days prior to the fluorescence imaging

Also known as: Humira

1. Fluorescence imaging of inflammatory bowel disease and rheumatoid arthritis with adalimumab-800CW; 2. Fluorescence imaging of inflammatory bowel disease and rheumatoid arthritis with adalimumab-800CW; 3. Fluorescence imaging of inflammatory bowel disease and rheumatoid arthritis with adalimumab-800CW

Fluorescence Imaging DEVICE

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 colonoscopy.

Also known as: Quantified fluorescence molecular endoscopy

1. Fluorescence imaging of inflammatory bowel disease and rheumatoid arthritis with adalimumab-800CW; 2. Fluorescence imaging of inflammatory bowel disease and rheumatoid arthritis with adalimumab-800CW; 3. Fluorescence imaging of inflammatory bowel disease and rheumatoid arthritis with adalimumab-800CW; 4. Fluorescence imaging of inflammatory bowel disease and rheumatoid arthritis

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Medical Center Groningen: lead
• AbbVie: collaborator

Study Sites (1)

University Medical Center Groningen

Groningen, Provincie Groningen, 9713 GZ, Netherlands

RECRUITING

MeSH Terms

Conditions

Arthritis, Rheumatoid; Inflammatory Bowel Diseases

Interventions

Adalimumab; Optical Imaging

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Officials

• Wouter B. Nagengast, MD, PhD, PharmD

  University Medical Center Groningen

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wouter B. Nagengast, MD, PhD, PharmD

CONTACT

+31503612620; w.b.nagengast@umcg.nl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 25, 2019
• First Posted: May 6, 2019
• Study Start: August 6, 2024
• Primary Completion: March 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: August 19, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)