Fluorescence Imaging of IBD and RA Using Adalimumab-800CW (STRATIFY)

University Medical Center Groningen (UMCG)

Status and phase: Enrolling; Phase 2

Conditions: IBD; Rheumatoid Arthritis

Treatments: Drug: Adalimumab-800CW; Device: Fluorescence Imaging

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03938701

NL75246.042.20

Details and patient eligibility

About

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.

Full description

See brief summary

Enrollment: 36 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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36 participants in 4 patient groups

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

Experimental group

Description:

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

Treatment:

Device: Fluorescence Imaging

Drug: Adalimumab-800CW

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

Experimental group

Description:

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

Treatment:

Device: Fluorescence Imaging

Drug: Adalimumab-800CW

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

Experimental group

Description:

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

Treatment:

Device: Fluorescence Imaging

Drug: Adalimumab-800CW

4. Fluorescence imaging of inflammatory bowel disease and rheumatoid arthritis

Experimental group

Description:

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

Treatment:

Device: Fluorescence Imaging