Fluorescence Imaging of Adalimumab-680LT in Inflammatory Bowel Disease

NCT06117423 | Recruiting Phase 1

• 2 other identifiers: 181462023-508391-11-00
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

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).

Conditions

Crohn Disease; Ulcerative Colitis

Keywords

Fluorescence Molecular Endoscopy; Inflammatory Bowel Disease; Adalimumab-680LT

Outcome Measures

Primary Outcomes (7)

• Determine the safety of adalimumab-680LT in IBD

  Evaluating possible (severe) adverse events (SAE \& AEs)

  Until 24 hours after administration

• Blood pressure

  Millimeters of mercure (mmHg)

  Five minutes before, and five and sixty minutes after tracer administration

• Heart rate

  Beats per minute

  Five minutes before, and five and sixty minutes after tracer administration

• Temperature

  Degrees Celsius

  Five minutes before, and five and sixty minutes after tracer administration

• Investigate the feasibility of using FME to detect adalimumab-680LT signals

  Evaluating the performance of FME for detecting adalimumab-680LT signals. This evaluation will be based on a visual evaluation during FME (visible signal yes/no), TBR and CNR calculations and MDSFR/SFF measurements.

  12 months

• Investigate the feasibility of using ex vivo FMI to detect adalimumab-680LT

  Evaluating the performance of ex vivo FMI for detecting adalimumab-680LT signals. This evaluation will be based on mean fluorescence intensities (MFIs) of biopsies and fluorescence/light sheet microscopy.

  12 months

• Determining the optimal imaging dose of adalimumab-680LT

  The optimal dose will be based on the adalimumab-680LT signals during FME and ex vivo FMI

  12 months

Secondary Outcomes (5)

• 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

  12 months

• 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

  12 months

• 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

  12 months

• To correlate ex vivo fluorescence signals to inflammation severity and tracer dose based on histopathological examination inside the obtained biopsies

  12 months

• 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

  12 months

Study Arms (5)

No administration of adalimumab-680LT

OTHER

Patients did not receive adalimumab-680LT, but underwent a Fluorescence Molecular Imaging procedure to serve as a control group and compare results with patients receiving the tracer

Other: Control

4.5 mg adalimumab-680LT

EXPERIMENTAL

Patients received 4.5 mg adalimumab-680LT and underwent a Fluorescence Molecular Imaging procedure

Drug: Adalimumab-680LT

15 mg adalimumab-680LT

EXPERIMENTAL

Patients received 15 mg adalimumab-680LT and underwent a Fluorescence Molecular Imaging procedure

Drug: Adalimumab-680LT

25 mg adalimumab-680LT

EXPERIMENTAL

Patients received 25 mg adalimumab-680LT and underwent a Fluorescence Molecular Imaging procedure

Drug: Adalimumab-680LT

>14 weeks of adalimumab therapy + optimal dose adalimumab-680LT

EXPERIMENTAL

Patients who received the optimal dose during the first Fluorescence Molecular Imaging procedure are invited for a second procedure after at least 14 weeks of adalimumab therapy. They will receive the optimal dose adalimumab-680LT and will undergo another Fluorescence Molecular Imaging procedure

Drug: Adalimumab-680LT

Interventions

Adalimumab-680LT DRUG

First, adalimumab-680LT was administered intravenously. 2-3 days later, a Fluorescence Molecular Imaging procedure was performed to enable the visualisation and detection of fluorescence signals.

15 mg adalimumab-680LT; 25 mg adalimumab-680LT; 4.5 mg adalimumab-680LT; >14 weeks of adalimumab therapy + optimal dose adalimumab-680LT

Control OTHER

Fluorescence Molecular Imaging was performed to enable the visualisation and detection of fluorescence signals.

No administration of adalimumab-680LT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Established IBD diagnosis (UC or CD)
• 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.

You may not qualify if:

• 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
• Active extra gastrointestinal manifestations of Crohn's disease
• Previous treatment with adalimumab and detectable anti-adalimumab antibodies levels

Sponsors & Collaborators

• University Medical Center Groningen: lead

Study Sites (1)

University Medical Center Groningen

Groningen, 9713GZ, Netherlands

RECRUITING

MeSH Terms

Conditions

Crohn Disease; Colitis, Ulcerative; Inflammatory Bowel Diseases

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Colitis; Colonic Diseases

Central Study Contacts

Wouter B Nagengast, MD, PhD, PharmD

CONTACT

+31(0)503612620; w.b.nagengast@umcg.nl

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: prof. dr.

Study Record Dates

• First Submitted: October 23, 2023
• First Posted: November 7, 2023
• Study Start: March 1, 2024
• Primary Completion: December 1, 2024
• Study Completion: June 1, 2025
• Last Updated: March 12, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)