Targeted Fluorescence Imaging in AMD (LEAF)

Targeted Fluorescence Imaging Using Bevacizumab-800CW Within Age-related Macular Degeneration (AMD) Patients to Evaluate the Upregulation of VEGF

Rationale:

To track performance of intravitreal distribution of anti-VEGF-A (Bevazicumab-800CW) and provide information about neovascularization and inflammation in Age-Related Macular Degeneration (AMD), thereby predicting progression and optimizing treatment

Objective:

To determine the safety and feasibility of fluorescence imaging of the eye with the fluorescent tracer bevacizumab-800CW for identification AMD with scanning laser angiography

Study design:

A non-randomized, non-blinded, prospective, single-center feasibility study.

Study population:

Patients group: patients with naïve wet AMD and wet AMD aged >60 years old with current treatment of anti-VEGF intravitreal.

Control group: patients with naïve wet AMD and wet AMD aged >60 years old with current treatment of anti-VEGF intravitreal

Intervention (if applicable):

Intravenous injection of bevacizumab-800CW in the patient group and vedolizumab-800CW in the control group.

Main study parameters/endpoints:

Safety and feasibility of the intravenous tracer bevacizumab-800CW in patients with naïve wet AMD and wet AMD by observing the uptake in retinal, choroid and neovascular tissue.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: No risk described in other (running) studies on intravenous injection with bevacizumab-800 CW. Patients need to come back 48-96 hours after injection and the eye measurements take about half an hour longer.

There is no benefit with participation.

Study Overview

• Status: Recruiting
• Conditions: Age-Related Macular Degeneration
• Intervention / Treatment: Drug: Bevacizumab-IRDye800CW; Drug: Vedolizumab-IRDye800CW

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands, 9713GZ
    • Recruiting
    • University Medical Center Groningen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with either naïve wet AMD or wet AMD receiving standard care of anti-VEGF therapy
• Aged >60 years old

Optional: Patients already included in fluorescence study which involves Bevacizumab-800CW

Exclusion Criteria:

• Eye pathology interfering with retinal imaging;
• Patients with psychological diseases or medical issues who are not able to sign informed consent form;
• Concurrent uncontrolled medical conditions;
• Received a different investigational drug within 30 days prior to the dose of bevacizumab-800CW;
• History of infusion reactions to bevacizumab or other monoclonal antibody.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: AMD with bevacizumab-800CW; Patients with AMD receive bevacizumab-800CW followed by angiography	Drug: Bevacizumab-IRDye800CW; Bevacizumab-800CW is administered to the patient and angiography is performed before and directly after tracer administration and after 48-96 hours.
Placebo Comparator: AMD with vedolizumab-800CW; Patients with AMD receive vedolizumab-800CW followed by angiography	Drug: Vedolizumab-IRDye800CW; Vedolizumab-800CW is administered to the patient and angiography is performed before and directly after tracer administration and after 48-96 hours.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety: number of participants with symptoms or changes in vital signs (blood pressure, heart rate and temperature) that are related to administration of bevacizumab-800CW	To determine the safety of bevacizumab-800CW in patients with AMD by monitoring of vital signs (blood pressure, heart rate and temperature), before and until one hour after administration.	Directly after administration until 96 hours after.
Feasibility: the possibility of measuring the specific uptake of fluorescence within the eye using both scanning laser angiography and optical coherence tomography.	The target-to-background radio will be measured during fluorescence imaging and compared with imaging before tracer administration.	Directly after administration until 96 hours after

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determination of the most optimal dose of bevacizumab-800CW for fluorescence imaging of the eye vascularization.	The target-to-background radio will be calculated and the dose with the highest ratio will be used as most optimal dose.	Directly after administration until 96 hours after.
Verification the specific uptake of bevazicumab-800CW by comparing the target-to-background ratio to the control antibody vedolizumab-800CW	The target-to-background of bevacizumab-800CW and vedolizumab-800CW will be compared.	Up to 1 year
Correlation between fluorescence intensity and clinical score	The subtype and severity of neovascularization will be determined and used as a clinical score.	Up to 1 year
Correlation of VEGF expression within the tear fluid with the fluorescent signal	Gather tear fluid with Schirmer strips and using ELISA to extract the VEGF concentration and correlate this with the fluorescence signal	Up to 1 year
Correlation of the fluorescence intensity, target-to-background ratio (TBR), with disease identification	The target-to-background ratio will be calculated and compared to the disease identification scale.	Up to 1 year

Collaborators and Investigators

• Sponsor: University Medical Center Groningen

Study record dates

Study Major Dates

• Study Start (Actual): October 28, 2022
• Primary Completion (Anticipated): September 30, 2023
• Study Completion (Anticipated): September 30, 2023

Study Registration Dates

• First Submitted: November 19, 2021
• First Submitted That Met QC Criteria: March 1, 2022
• First Posted (Actual): March 2, 2022

Study Record Updates

• Last Update Posted (Actual): March 23, 2023
• Last Update Submitted That Met QC Criteria: March 21, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Physiological Effects of Drugs; Antineoplastic Agents; Gastrointestinal Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab; Vedolizumab
• Other Study ID Numbers: NL78391.056.21

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No