Evaluation of 68Ga-NODAGA-RGD PET Imaging for Monitoring Therapeutic Response in Unilateral Age-Related Macular Degeneration Patients

The primary objective of this study is to evaluate the ability of **68Ga-NODAGA-RGD PET imaging** to demonstrate a molecular therapeutic response in patients with unilateral **age-related macular degeneration (AMD)** following intraocular antiangiogenic injections. This assessment is conducted at the end of the induction phase, which occurs after three months of treatment. The clinical relevance of this objective lies in its potential to provide a non-invasive method for monitoring the effectiveness of antiangiogenic therapy in AMD, thereby aiding in the optimization of treatment strategies for this prevalent ocular condition.

Secondary objectives include:

• Measuring the relationship between **68Ga-NODAGA-RGD PET** signal intensity (SUVmax) and retinal thickness, as measured by optical coherence tomography (OCT), for each eye before treatment and after the sixth intraocular injection of the antiangiogenic agent.
• Assessing the relationship between **68Ga-NODAGA-RGD PET** signal intensity (SUVmax) and visual acuity, as measured by the ETDRS and Parinaud scales, for each eye before treatment and after the sixth intraocular injection of the antiangiogenic agent.

The clinical trial focuses on evaluating the ability of **68Ga-NODAGA-RGD PET imaging** to demonstrate a molecular therapeutic response in patients with **age-related macular degeneration** (AMD). The study population includes both male and female participants aged 18 years and older, with a specific focus on individuals diagnosed with unilateral AMD. Participants must have at least one focus of choroidal neovascularization on OCT and must be naïve to any antiangiogenic treatment. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants. Key lifestyle considerations such as diet and physical activity are not specified. Participants are required to have an initial check-up, including OCT and visual acuity measurement, conducted within one month prior to the **68Ga-NODAGA-RGD PET scan**. Additionally, participants must be affiliated with a social security scheme and have signed informed consent. The selection process for the trial population is not detailed in the provided data.

The clinical trial is designed to evaluate the efficacy of **68Ga-NODAGA-RGD** PET imaging in assessing the molecular therapeutic response in patients with unilateral **age-related macular degeneration** (AMD). This is a phase 4, randomized, double-blind, controlled trial with an estimated duration from October 2022 to January 2025. The trial involves 20 participants who meet the inclusion criteria, such as being 18 years or older, having unilateral AMD with choroidal neovascularization, and being naïve to antiangiogenic treatment. Participants must provide signed informed consent and be affiliated with a social security scheme.

The trial consists of several key visits: an initial screening visit, follow-up visits, and an end-of-study visit. The screening visit will confirm eligibility through assessments like optical coherence tomography (OCT) and visual acuity measurement, conducted within one month prior to the PET scan. Follow-up visits will occur at baseline (M0) and four months (M4) to compare PET signal intensity ratios (SUVmax) between the AMD and contralateral eyes. Secondary endpoints include correlating PET signal intensity with retinal thickness and visual acuity scores at these time points.

Participants are expected to be involved in the study for a maximum of four months, with the possibility of early termination if they experience adverse effects or fail to comply with study protocols. The investigational product, **68Ga-RGD 15MBq/mL prep**, is administered intravenously as a solution for injection, with a maximum daily dose of 2.5 MBq/kg. The trial aims to provide insights into the potential of PET imaging as a tool for monitoring therapeutic responses in AMD patients.

The clinical trial involves the use of an **experimental medication** known as 68Ga-RGD 15MBq/mL prep, which is a **solution for injection**. The active substance in this medication is 5-[4-[(2S,5S,11S,14R)-14-benzyl-11-(carboxymethyl)-5-[3-(diaminomethylideneamino)propyl]-3,6,9,12,15-pentaoxo-1,4,7,10,13-pentazacyclopentadec-2-yl]butylamino]-2-[4,7-bis(carboxymethyl)-1,4,7-triazonan-1-yl]-5-oxopentanoic acid radio-labeled with **gallium-68**. This compound is also known by the synonym 68Ga-NODAGA-RGD. The medication is administered intravenously, with a maximum daily dose of 2.5 MBq/kg and a maximum total dose of 2.5 MBq/kg. The treatment period is limited to a maximum of 2 days. The pharmaceutical form of the medication is a solution for injection, and it is not a pediatric formulation.

In this study, the experimental medication is used to evaluate the ability of 68Ga-NODAGA-RGD PET imaging to demonstrate a molecular therapeutic response in patients with unilateral **age-related macular degeneration (AMD)**. The trial aims to assess the response to intraocular antiangiogenic injections at the end of the induction phase, which occurs after 3 months of treatment. The study does not involve any non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatment. Participant compliance with the dosing schedule is monitored to ensure adherence to the protocol.

Efficacy in this clinical trial will be assessed through the use of **68Ga-NODAGA-RGD PET imaging** to evaluate the molecular therapeutic response in patients with unilateral age-related macular degeneration (AMD). The primary endpoint involves comparing the PET signal intensity ratios (SUVmax) of the AMD-affected and contralateral eyes at baseline (M0) and after four months (M4) using a paired means comparison test. Secondary endpoints include documenting the relationships between PET signal intensity (SUVmax) and retinal thickness measured by optical coherence tomography (OCT) for each eye, as well as the correlation between PET signal intensity (SUVmax) and visual acuity scores measured with psychometric scales (ETDRS and Parinaud) at M0 and M4. These assessments will provide insights into the efficacy of intraocular antiangiogenic injections over the course of the treatment period.