Evaluation of Safety, Feasibility, and Optimal Dosing of Fluorescently Labeled Adalimumab-680LT in Patients with Inflammatory Bowel Disease

The primary objective of this study is to evaluate the **safety** of adalimumab-680LT in patients with **Inflammatory Bowel Disease (IBD)**. This will be achieved by monitoring vital signs, assessing the injection site, and evaluating potential tracer-related severe adverse events (SAEs) and suspected unexpected serious adverse reactions (SUSARs). Additionally, the study aims to investigate the feasibility of using fluorescence molecular endoscopy (FME) and ex vivo fluorescence molecular imaging (FMI) to detect adalimumab-680LT signals and determine the most optimal imaging dose. These objectives are clinically relevant as they aim to ensure patient safety and optimize the use of adalimumab-680LT for effective visualization of drug targeting in IBD.

Secondary objectives include: - Investigating the correlation between in vivo and ex vivo fluorescence signal intensities and target saturation with clinical response/remission after 14 weeks of adalimumab therapy. - Quantifying the fluorescence signals of the tracer in vivo using single-fiber reflectance/single-fiber fluorescence spectroscopy and correlating these measurements to tracer dose, in vivo fluorescence intensities, and inflammation severity. - Correlating ex vivo fluorescence signals to inflammation severity and tracer dose based on histopathological examination of biopsies. - Assessing tracer stability, distribution, concentration, and identifying the composition of immune cells ex vivo to gain insights into adalimumab mucosal target cells.

The clinical trial involves participants diagnosed with **Inflammatory Bowel Disease (IBD)**, specifically those with either ulcerative colitis (UC) or Crohn's disease (CD). The study population includes both male and female subjects, aged 18 years and older, who are eligible for adalimumab therapy. Participants must have clinically active disease, as defined by specific scoring indices, and biochemically active disease, indicated by a fecal calprotectin level greater than 60 µg/g. The trial does not include a vulnerable population. The sponsor has not provided the total number of participants. All participants are required to provide written informed consent and have a clinical indication for an endoscopic procedure. Lifestyle factors such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the **safety** and feasibility of using fluorescently labeled **adalimumab-680LT** in patients with **Inflammatory Bowel Disease (IBD)**. This is a Phase 2, randomized, double-blind, controlled trial. The trial aims to assess the safety of adalimumab-680LT by monitoring vital signs, injection sites, and evaluating potential tracer-related severe adverse events (SAEs) and suspected unexpected serious adverse reactions (SUSARs). Additionally, the trial investigates the feasibility of using fluorescence molecular endoscopy (FME) and ex vivo fluorescence molecular imaging (FMI) to detect adalimumab-680LT signals and determine the optimal imaging dose.

The trial is expected to commence recruitment on February 1, 2024, and conclude by December 31, 2024. Participants will be involved in the study for a minimum of 14 weeks. The study includes several key visits: an initial screening visit to confirm eligibility, follow-up visits to monitor safety and efficacy, and an end-of-study visit to assess final outcomes. The inclusion criteria require participants to have an established diagnosis of IBD, be eligible for adalimumab therapy, and provide written informed consent. Participants must also have clinically active disease and a clinical indication for an endoscopic procedure.

Primary endpoints include monitoring vital signs before and after tracer administration and evaluating possible adverse events. Secondary endpoints involve comparing in vivo fluorescence images and other measurements before and after at least 14 weeks of adalimumab treatment. Participants may be terminated early from the study if they experience severe adverse reactions or if they withdraw consent. The trial will utilize Humira 40 mg solution for injection in pre-filled syringes, administered subcutaneously. The study is not a low-intervention trial and is categorized as a Phase 2 intervention trial.

The clinical trial involves the use of **adalimumab**, marketed under the name Humira, as the experimental medication. Humira is formulated as a **solution for injection** in a pre-filled syringe, containing 40 mg of the active substance. The pharmaceutical form is specifically designed for **subcutaneous** administration. The trial aims to investigate the safety, feasibility, and optimal dose of adalimumab labeled with IRDye 680LT for visualizing drug targeting in patients with Inflammatory Bowel Diseases. The administration frequency and dosing schedule are determined based on the study protocol, with careful monitoring of participant compliance and any potential adverse events.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus is solely on the experimental use of adalimumab-680LT. The trial includes monitoring of vital signs, the injection site, and evaluation of possible tracer-related severe adverse events (SAEs) and suspected unexpected serious adverse reactions (SUSARs). The feasibility of using fluorescence molecular endoscopy (FME) and ex vivo fluorescence molecular imaging (FMI) to detect adalimumab-680LT signals is also assessed to determine the most optimal imaging dose.

Efficacy in this clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoints include monitoring vital signs before and after the administration of the tracer and evaluating possible severe adverse events (SAEs) and adverse events (AEs). Additionally, visual evaluation during fluorescence molecular endoscopy (FME) will be conducted to determine the presence of visible signals, along with calculations of target-to-background ratio (TBR) and contrast-to-noise ratio (CNR). Mean fluorescence intensities (MFIs) of biopsies, MDSFR/SFF measurements, and fluorescence/light sheet microscopy will also be utilized.

Secondary endpoints involve the comparison of in vivo fluorescence images, MFIs of biopsies, MDSFR/SFF measurements, fluorescence microscopy results, and tracer concentrations inside biopsies before and after at least 14 weeks of **adalimumab** treatment. Quantification of MDSFR/SFF measurements in inflamed tissue compared to non-inflamed tissue will be performed, with an investigation into the correlation between MDSFR/SFF measurements and dose/inflammation severity. Histological analysis will categorize tissue types as normal (non-inflamed) or inflamed in the ileum, colon, and rectum, as well as random high-fluorescent and non-fluorescent tissues.

Fluorescence (confocal) microscopy will be employed with additional immune panels and spatial transcriptomics analysis before and after at least 14 weeks of **adalimumab** treatment. Measurements of the **adalimumab-680LT** concentration will be conducted using light-sheet microscopy after tissue clearing. Insights into **adalimumab**-target cells and the presence of immune cells inside biopsies and blood samples will be obtained through flow cytometry, and tracer stability will be assessed by Western Blot.