Clinical trial NCT06117423: Fluorescence Imaging of Adalimumab-680LT in Inflammatory Bowel Disease
Official title: Investigating the Safety, Feasibility, and Optimal Dose of Fluorescently Labeled Adalimumab-680LT for Visualizing Drug Targeting in Inflammatory Bowel Diseases
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Crohn Disease
Ulcerative Colitis
Keywords: Fluorescence Molecular Endoscopy
Inflammatory Bowel Disease
Adalimumab-680LT
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
First posted: 2023-11-07
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: OTHER

Brief summary: Crohn's Disease (CD) and Ulcerative Colitis (UC) are chronic inflammatory bowel diseases (IBD). Adalimumab is a human monoclonal antibody against TNF-alpha, a pro-inflammatory cytokine that mediates the inflammatory response in IBD upon binding to the TNF receptors. Primary non-response to adalimumab is high in both CD and UC. Currently, there are no predictors of response to adalimumab and the actual mechanism of action has not yet been elucidated. To gain better understanding of the drug targeting of adalimumab in IBD, the University Medical Center Groningen (UMCG) developed fluorescently labeled adalimumab (adalimumab-680LT). This study aims to assess the safety and the optimal dose of adalimumab-680LT to visualize and potentially quantify the local drug concentration and predict treatment response in IBD patients using in vivo and ex vivo fluorescence molecular imaging (FMI).


Eligibility criteria: Inclusion Criteria:

* Established IBD diagnosis (UC or CD)
* Active disease (clinically defined as at least mild activity using dedicated scoring indices and biochemically defined by a fecal calprotectin \> 60 µg/g, measured within the last 6 weeks before inclusion)
* Patients must be eligible for adalimumab therapy
* Clinical indication for an endoscopic procedure
* Age: 18 years or older
* Written informed consent
* For female patients of premenopausal age with intact reproductive organs or who are less than 2 years postmenopausal, a negative pregnancy test must be available.

Exclusion Criteria:

* Pregnancy or breast feeding
* Female patient of premenopausal age who does not use any reliable form of contraception at the time of adalimumab-680LT administration and the following 10 weeks.
* Medical or psychiatric conditions that compromise the patient's ability to give informed consent
* Prior anti-TNF therapy in the last 6 weeks before inclusion
* Active extra gastrointestinal manifestations of Crohn's disease
* Previous treatment with adalimumab and detectable anti-adalimumab antibodies levels

Primary outcomes:
measure: Determine the safety of adalimumab-680LT in IBD
timeFrame: Until 24 hours after administration
measure: Blood pressure
timeFrame: Five minutes before, and five and sixty minutes after tracer administration
measure: Heart rate
timeFrame: Five minutes before, and five and sixty minutes after tracer administration
measure: Temperature
timeFrame: Five minutes before, and five and sixty minutes after tracer administration
measure: Investigate the feasibility of using FME to detect adalimumab-680LT signals
timeFrame: 12 months
measure: Investigate the feasibility of using ex vivo FMI to detect adalimumab-680LT
timeFrame: 12 months
measure: Determining the optimal imaging dose of adalimumab-680LT
timeFrame: 12 months
Secondary outcomes:
measure: Investigate a potential correlation of in vivo fluorescence signal intensities and target saturation to clinical response/remission after 14 weeks of adalimumab therapy regimen in patients with IBD
timeFrame: 12 months
measure: Investigate a potential correlation of ex vivo fluorescence signal intensities and target saturation to clinical response/remission after 14 weeks of adalimumab therapy regimen in patients with IBD
timeFrame: 12 months
measure: Quantify the fluorescence signals of the tracer in vivo by using single-fiber reflectance/single-fiber fluorescence (MDSFR/SFF) spectroscopy and correlate these measurements to tracer dose, in vivo fluorescence intensities and inflammation severity
timeFrame: 12 months
measure: To correlate ex vivo fluorescence signals to inflammation severity and tracer dose based on histopathological examination inside the obtained biopsies
timeFrame: 12 months
measure: To assess tracer stability, tracer distribution and tracer concentration, and to identify the composition of immune cells ex vivo to learn more about adalimumab mucosal target cells
timeFrame: 12 months
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
Study officials:
References: