Fluorescence Imaging of IBD and RA Using Adalimumab-800CW
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity Medical Center Groningen
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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;
Disqualifiers
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
Design model
Single group
Treatments tested in this trial
Adalimumab-800CW
DrugIntravenous administration of 4.5 mg, 15 mg or 25 mg 2 - 4 days prior to the fluorescence imaging
Fluorescence Imaging
DeviceRheumatoid 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.
Treatment groups
36 Participants
are divided into 4 treatment groupsGroup A: 1. Fluorescence imaging of inflammatory bowel disease and rheumatoid arthritis with adalimumab-800CWExperimental treatment 2 interventions
Group B: 2. Fluorescence imaging of inflammatory bowel disease and rheumatoid arthritis with adalimumab-800CWExperimental treatment 2 interventions
Group C: 3. Fluorescence imaging of inflammatory bowel disease and rheumatoid arthritis with adalimumab-800CWExperimental treatment 2 interventions
Group D: 4. Fluorescence imaging of inflammatory bowel disease and rheumatoid arthritisExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
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.
Time frame
Up to 30 minutes after stop tracer injection2
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.
Time frame
Up to 24 hours after tracer injection3
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.
Time frame
Up to 1 year4
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.
Time frame
Up to 1 yearSecondary outcomes
1
The correlation between the fluorescence intensity and the disease activity measured with the DAS28 in patients with RA.
The DAS28 (Disease Activity Score 28) is developed and validated by the EULAR (European League Against Rheumatism) to measure the progress and improvement of Rheumatoid Arthritis by measuring 28 joints. When looking at these joints, both the number of joints with tenderness upon touching and swelling are counted. Furthermore, the erythrocyte sedimentation rate is measured and a patients assessment of disease activity during the preceding 7 days is measured on a scale between 0 and 100, where 0 is 'no activity' and 100 is 'highest activity possible'. DAS28 values range from 0.49 to 9.07 while higher values mean a higher disease activity. A DAS28 below the value of 2.6 is interpreted as Remission. Between 2.6 and 3.2 as low disease activity, and between 3.2 and 5.1 as moderate. Above 5.1 is indicated as high disease activity.
Time frame
Up to 1 year2
Calculation of optical properties with MDSFR/SFF spectroscopy in patients with RA
To quantify the optical properties, in vivo using multi-diameter single-fiber reflectance, single-fiber fluorescence (MDSFR/SFF) spectroscopy measurements;
Time frame
Up to 1 year3
The correlation between fluorescence intensity and the clinical disease activity score in ulcerative colitis using the SCCAI;
The SCCAI is a diagnostic questionnaire to assess the severity of symptoms in patients with ulcerative colitis. The score ranges from 0 to 19 based on questions on topics regarding the bowel frequency, urgency of defecation, blood in stool and general health. A score of 5 or higher indicates active disease.
Time frame
Up to 1 year4
The correlation between fluorescence intensity and the endoscopic disease activity score in ulcerative colitis using the Mayo endoscopic subscore;
The endoscopic Mayo Score (Mayo endoscopic subscore) evaluates ulcerative colitis stage, based only on endoscopic exploration. Endoscopic activity is based upon the assessment of a few features, such as the presence of erythema, visibility of the vascular pattern, friability, erosions, spontaneous bleeding and (large) ulcerations. Each score indicates endoscopic activity: 0 = inactive disease tot 3 = severely active disease. 3-5 = mild activity 6-10 = moderate activity \>10 = severe activity
Time frame
Up to 1 yearSponsors and contacts
Click on the lead sponsor to view all of their trials.
University Medical Center Groningen
Lead sponsor
AbbVie
Collaborator
Source ClinicalTrials.gov