Evaluation of Ranibizumab with or without Early Targeted Peripheral Laser Photocoagulation in Macular Edema Secondary to Central Retinal Vein Occlusion

The primary objective of this study is to assess whether the duration of guideline-conform periodic **ranibizumab** injections can be reduced or successfully terminated in patients with **macular edema** due to central retinal vein occlusion when early targeted peripheral laser photocoagulation is applied concurrently. This is clinically relevant as it may lead to a reduction in treatment burden and potential side effects associated with prolonged anti-VEGF therapy.

Secondary objectives include:

• Evaluating visual acuity during and after the intervention, quality of life aspects, and potential issues related to the intervention. Key endpoints are best corrected visual acuity (BCVA), central subfield thickness (CST), and the number of ranibizumab injections required until treatment success and up to the end of observation.
• Assessing the proportion of subjects developing neovascularization over the observation period, health-related quality of life (HrQoL), the area of non-perfusion, vessel density, and the area of the foveal avascular zone, potential visual field loss, development of collaterals, and the number of laser treatments and laser spots in the experimental group.
• Comparing the safety profile of the combined intervention to the guideline-based standard intervention in terms of adverse events (AEs) and serious adverse reactions (SARs) occurrence until four weeks after the last trial-related intervention, with critical ocular events evaluated until the end of the study.

The clinical trial focuses on patients diagnosed with **macular edema due to central retinal vein occlusion**. The study population includes both male and female participants aged 18 years and older. Participants are required to have a foveal thickness greater than 250 μm, as measured by OCT, and a BCVA score in the study eye between 24 and 78 letters on the ETDRS chart. The trial does not involve a vulnerable population. Participants must have a history of central retinal vein occlusion no longer than six months and exhibit capillary non-perfusion in the peripheral retina larger than five disc areas, documented through ultra wide-field fluorescein angiography. The ability and willingness to attend all scheduled visits and assessments are also necessary. The sponsor has not provided information regarding the total number of participants in the trial.

The clinical trial is designed to evaluate the efficacy of **ranibizumab** injections, with or without early targeted peripheral laser photocoagulation, in treating **macular edema** due to central retinal vein occlusion. This study is a randomized, double-blind, controlled trial, categorized as a low interventional clinical trial, and is in phase 5. The trial aims to determine if the duration of periodic ranibizumab injections can be shortened or successfully terminated when combined with laser photocoagulation. The trial is expected to run from August 26, 2020, to August 31, 2026, with a maximum treatment period of 23 months for each participant.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as a diagnosis of macular edema due to central retinal vein occlusion, age of 18 years or older, and a history of central retinal vein occlusion no longer than six months. The inclusion visit will also involve obtaining written informed consent and assessing the best corrected visual acuity (BCVA) and central subfield thickness (CST) using optical coherence tomography (OCT). Follow-up visits will occur regularly to monitor BCVA, CST, and the number of ranibizumab injections required. The primary endpoint is the time to treatment success, defined as the time from randomization until the last criteria-based intravitreal injection, followed by a treatment-free period of at least six months. Secondary endpoints include BCVA letter scores and CST measurements per visit.

The expected length of participant involvement is up to 29 months, including the observation period for late recurrence of macular edema. Conditions that may lead to early termination from the study include failure to meet the inclusion criteria, inability to attend scheduled visits, or adverse events that compromise participant safety. Participants will conclude their involvement with an end-of-study visit, where final assessments will be conducted to evaluate the long-term outcomes of the treatment regimen.

The clinical trial involves the administration of **RANIBIZUMAB**, an anti-VEGF (vascular endothelial growth factor) drug, for the treatment of macular edema due to central retinal vein occlusion. **RANIBIZUMAB** is provided in the form of a **solution for injection** and is administered via **intravitreal use**. The dosage is set at a maximum of 0.5 mg per administration, with the treatment period extending up to 23 weeks. The administration frequency is determined by the study protocol, which aims to evaluate the potential for reducing or terminating the need for periodic injections when combined with early targeted peripheral laser photocoagulation.

In addition to the experimental treatment, the study may involve the use of standard-of-care therapies as deemed necessary by the clinical investigators. These therapies are not experimental and are used to provide comprehensive care to participants, ensuring that all patients receive the best possible treatment for their condition. Compliance with the dosing schedule and administration protocol is monitored throughout the study to ensure adherence and to evaluate the efficacy and safety of the treatment regimen.

Efficacy in the clinical trial titled "Long-term need of Ranibizumab injections with or without early targeted peripheral laser photocoagulation for treatment of macular edema due to central retinal vein occlusion (CoRaLa II trial)" will be assessed using both primary and secondary endpoints. The primary efficacy endpoint is defined as the time to treatment success, which is the duration from randomization until the last criteria-based intravitreal injection, followed by a treatment-free period of at least six months. This endpoint will be evaluated based on objective criteria for further treatment indications.

Secondary endpoints include the assessment of best corrected visual acuity (BCVA) using BCVA letter scores from ETDRS charts at each visit, and the measurement of central subfield thickness (CST) via optical coherence tomography (OCT) at each visit. Additionally, the number of **Ranibizumab** injections required after the initial three monthly injections, according to re-treatment criteria, will be recorded until treatment success is achieved or up to 29 months post-randomization, accounting for any late recurrence of macular edema. These parameters will be systematically collected and analyzed to determine the efficacy of the treatment regimen.