Targeted Fluorescence Imaging in AMD

Study Overview
=================
Brief Summary
-----------------
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.

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

Conditions
-----------------
Age-Related Macular Degeneration

Intervention / Treatment
-----------------
* Drug: Bevacizumab-IRDye800CW
* Drug: Vedolizumab-IRDye800CW


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: First a dose finding study is performed using bevacizumab-800CW within the AMD patient group. Using the optimal dose and if fluorescence is visible, the vedolizumab group is added.
Masking: None (Open Label)


Arms and Interventions

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

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. | 
| 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 | 
| 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 |