The purpose of this amendment was to incorporate changes requested by Regulatory Authorities. Clarification of the washout period between the last dose of the anti-VEGF treatment received by the patient prior to be included in the study and the first dose of brolucizumab 6 mg administrated in the study. Clarification on the number of mandatory visits and on the data to collect for the fellow eye.

The purpose was to provide clarification and guidance on safety assessments in accordance to the urgent safety measures regarding the post-marketing reports with brolucizumab 6 mg (Beovu®) in the treatment of nAMD. Restrictions in the use of corticosteroids were removed to provide flexibility using systemic steroids for the treatment of AEs at the Investigator’s discretion. Additional guidance was added to emphasize that if any sign of IOI was present, an IVT injection were not to be performed and patients were to be treated for IOI according to clinical practice. Additional examinations and assessments were included to fully characterize cases of IOI. The number of study sites was increased from 50 to 75 to ensure the feasibility of patient recruitment in a 9-month period. Instructions on ophthalmic examinations in case of symptoms of IOI were added.

As per the urgent safety measures, clarification and guidance were provided on the early discontinuation of study treatment required for those patients who were on q4w dosing beyond the first 3-monthly loading phase or would need q4w dosing beyond the “loading phase” based on the Investigator’s assessment. Discontinuation of study treatment for patients who develop RV and/or RVO was added in line with the urgent safety measures. The safety sections were updated throughout the protocol including updating the Risks and Benefits section and creating a new section under Safety Monitoring to consolidate all the information regarding the risk mitigation into one section in the protocol and require close monitoring of patients with IOI. Clarification was provided on record of prior Intraocular or periocular use of corticosteroids in the study eye and remove of the study timelines and number of sites.

The optional Patient reported outcome (PRO) self-assessment of BCNVA by the patient at home was removed because of the scarce use by the elderly population of the study, which would not allow valid conclusions from data collected. The Warnings and Precautions for Use section of the Beovu® brolucizumab 6 mg EU SmPC was updated to indicate that patients treated with Beovu with a medical history of IOI and/or RVO should be closely monitored, and for patients who develop IOI, even if not associated with RV and/or RVO, treatment with Beovu should be discontinued and the events promptly managed. Information on gender imbalance on IOI following brolucizumab 6 mg treatment was added.

Due to COVID-19 and the urgent safety measures, the originally planned number of patients could not be achieved. Thus, the sample size was reassessed.