Long-Term Outcomes Evaluation of Aflibercept in Pediatric Retinopathy of Prematurity: An Extension of the VGFTe-ROP-1920 Study

The primary objectives of this extension study are to evaluate **binocular visual acuity** and long-term safety outcomes in patients who received treatment for **retinopathy of prematurity (ROP)** in the VGFTe-ROP-1920 study. These objectives are clinically relevant as they aim to assess the effectiveness and safety of the treatment over an extended period, providing valuable insights into the long-term management of ROP, a condition that can lead to visual impairment in premature infants.

Secondary objectives include:

• Describing visual function in patients from the VGFTe-ROP-1920 study.
• Describing overall development in these patients.

The clinical trial involves a total of **77 participants** who are being studied for the treatment of **retinopathy of prematurity (ROP)**. The study population includes both male and female subjects, all of whom are under 13 months of chronological age. Participants were selected based on their previous treatment in the VGFTe-ROP-1920 study. The trial population is considered vulnerable due to the young age of the participants. The study does not specify any particular lifestyle considerations such as diet or physical activity. The selection criteria required signed informed consent from the parent(s) or legal guardian(s), ensuring compliance with the study's requirements and restrictions.

The clinical trial is designed as a **randomized**, **double-blind**, and **controlled** study to evaluate the long-term outcomes of patients who received treatment for **retinopathy of prematurity (ROP)** in a previous study. The trial will assess the efficacy and safety of **aflibercept**, administered as a 40 mg/mL solution for injection via the **intravitreal route**. The study is expected to span approximately five years, with an estimated end date in November 2026.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as previous treatment in the VGFTe-ROP-1920 study, age under 13 months, and signed informed consent from parents or legal guardians. The primary objectives include evaluating binocular visual acuity and long-term safety outcomes. Primary endpoints will focus on binocular best-corrected visual acuity (BCVA) and the proportion of patients experiencing adverse events. Secondary endpoints will assess ocular structural outcomes, BCVA in each eye, refractive spherical equivalent, and neurodevelopmental outcomes using standardized assessments such as BSID-III, WPPSI-IV, and VABS-II.

Participants will be involved in the study for a maximum treatment period of 60 months. Follow-up visits will be scheduled periodically to monitor progress and collect data on both primary and secondary endpoints. The end-of-study visit will conclude the trial, where final assessments will be conducted to evaluate the long-term outcomes of the treatment. Conditions that may lead to early termination from the study include non-compliance with the protocol, withdrawal of consent, or the occurrence of serious adverse events that necessitate discontinuation of participation.

The clinical trial involves the administration of **Eylea**, a pharmaceutical product containing the active substance **aflibercept**. Eylea is formulated as a **solution for injection** and is provided in a vial with a concentration of 40 mg/mL. The route of administration is **intravitreal use**, which involves injecting the solution directly into the eye. The treatment is designed for patients who have previously participated in the VGFTe-ROP-1920 study for the treatment of retinopathy of prematurity. The maximum treatment period for this study is 60 days. The product is manufactured by Bayer AG and is not a pediatric formulation. The study does not specify a maximum daily or total dose amount, indicating that dosing will be determined based on clinical judgment and patient response.

In this clinical trial, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus is solely on evaluating the long-term outcomes and safety of Eylea in the specified patient population. Participant compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the treatment protocol. The study aims to assess binocular visual acuity and long-term safety outcomes in patients who received treatment for retinopathy of prematurity in the previous study.

Efficacy in this clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoints include the evaluation of **binocular best-corrected visual acuity (BCVA)** and the proportion of patients experiencing adverse events and serious adverse events. Secondary endpoints will focus on additional parameters such as the proportion of patients developing unfavorable ocular structural outcomes, BCVA in each eye, refractive spherical equivalent in each eye, and neurodevelopmental outcomes assessed using the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III), the Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition (WPPSI-IV), and the Vineland Adaptive Behavior Scales, Second Edition (VABS-II). Furthermore, the study will monitor the proportion of patients with recurrence of retinopathy of prematurity (ROP) and those requiring treatment for ROP.

The efficacy parameters will be measured and collected at specified timepoints throughout the study duration. The assessments will be conducted using validated scales and instruments appropriate for each endpoint. The data collected will be analyzed to determine the long-term outcomes of patients who received treatment for ROP in the VGFTe-ROP-1920 study. The study aims to provide comprehensive insights into the efficacy and safety of the treatment over an extended period.