Clinical trial NCT03938701: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: IBD
Rheumatoid Arthritis
Keywords: Molecular imaging
Adalimumab-800CW
Fluorescence
Inflammatory bowel disease
Rheumatoid arthritis
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
Collaborators: name: AbbVie
First posted: 2019-05-06
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: See brief summary

Eligibility criteria: Inclusion criteria:

* Established IBD or RA 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;
* No history of previous anti-TNF therapy (anti-TNF naïve);
* 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:

* The use of Methotrexate during the execution of the trial.
* 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.
* RA patients with a skin type above type 3 according to the Fitzpatrick scale due to feasibility of the MDSFR/SFF spectroscopy measurements.

Primary outcomes:
measure: 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
timeFrame: Up to 30 minutes after stop tracer injection
measure: Safety: number of participants with (serious) adverse events that are related to the administration of adalimumab-800CW
timeFrame: Up to 24 hours after tracer injection
measure: 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
timeFrame: Up to 1 year
measure: 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).
timeFrame: Up to 1 year
measure: 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).
timeFrame: Up to 1 year
Secondary outcomes:
measure: The correlation between the fluorescence intensity and the disease activity measured with the DAS28 in patients with RA.
timeFrame: Up to 1 year
measure: Calculation of optical properties with MDSFR/SFF spectroscopy in patients with RA
timeFrame: Up to 1 year
measure: The correlation between fluorescence intensity and the clinical disease activity score in ulcerative colitis using the SCCAI;
timeFrame: Up to 1 year
measure: The correlation between fluorescence intensity and the endoscopic disease activity score in ulcerative colitis using the Mayo endoscopic subscore;
timeFrame: Up to 1 year
measure: The correlation between fluorescence intensity and the clinical disease activity score in Crohn's disease using the Crohn's Disease Activity Index (CDAI).
timeFrame: Up to 1 year
measure: The correlation between fluorescence intensity and the disease activity score in Crohn's disease using the SES-CD score
timeFrame: Up to 1 year
measure: The correlation and validation of fluorescence signals detected in vivo to the pathology of biopsies for IBD patients;
timeFrame: Up to 1 year
measure: 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;
timeFrame: Up to 1 year
measure: Correlation in IBD between the detected fluorescence signals in vivo and the clinical response to induction therapy at week 14.
timeFrame: Up to 1 year
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
Study officials:
affiliation: University Medical Center Groningen
name: Wouter B. Nagengast, MD, PhD, PharmD
role: PRINCIPAL_INVESTIGATOR
References: