Correction of the inconsistent trial number in protocol header.

Part 1. The amendment included the following main changes: 1) substance name “BI 425809” replaced by “iclepertin”; 2) clarified that the key secondary efficacy endpoint for the VRFCAT is the total adjusted time T-score; 3) clarified that study partner is required for SCoRS and Positive and Negative Syndrome Scale (PANSS) interviews at least at Visit 2 and End of treatment (EOT); 4) changed the requirement for ophthalmologic assessments to be performed for all ocular adverse events (AEs), rather than only moderate to severe vision-related AEs; 5) clarified that Paxlovid™ should not be used concomitantly with the trial medication and that patients who required treatment with Paxlovid should be temporarily discontinued from trial medication; 6) revision of a further endpoint; 7) updates to inclusion and exclusion criteria; 8) added guidance related to patients who were lost to follow-up and included a reference to the retention guide; 9) removed the requirement to follow patients after permanent discontinuation of trial treatment until EOT plus 28 days; 10) revised the list of reasons for withdrawing individual patients from trial treatment to include needing to take restricted medications; 11) removed quetiapine as an example of restricted sedative medication; 12) clarified restriction on short term use of opioids for pain, cough, or diarrhoea; 13) added vaccination for Coronavirus disease 2019 (COVID-19) to the permitted therapies; 14) allowed re-testing for urine drug screen at Visit 1a if results were positive at Visit 1; 15) added requirement that all patients consent to use the AiCure application at screening but allowed randomised patients on treatment who refused to continue using the application to remain in the trial; 16) clarified that Verified Clinical Trials would be used only for countries that had not opted out by local amendment.

Part 2. 17) removal of examples of scales that should be done by the same rater; clarified that ideally, all scales should be performed by the same rater whenever possible; 18) clarified that the clinical global impression used in the trial should be based on the global impression including the patient’s functioning based on the SCoRS assessment; 19) clarified that patients could start trial procedures after providing written informed consent even if the study partner informed consent was not yet signed; 20) clarified the procedures for rolling over into the extension trial; 21) clarified that the randomised set would exclude patients randomised in error and discontinued from the trial before the start of trial medication; 22) updated the statistical model; 23) revised wording to indicate that the caregiver would be asked to complete the additional questionnaires; 24) clarified that in case of exceptional circumstances such as the COVID-19 pandemic, secondary endpoint assessments could not be performed remotely as it would reduce quality.

The amendment included the following main changes: 1) added footnote to the Flow Chart to state that Columbia Suicide Severity Rating Scale (C-SSRS) could be repeated based on investigator discretion; 2) based on DMC recommendation, reinforced documenting details of any positive suicidal ideation and providing comments on clinical significance and any additional follow-up action items; also added that the C-SSRS could be repeated at an unscheduled visit based on investigator discretion; 3) added substance use to the Flow Chart; 4) clarified calculation of treatment compliance based on tablets removed from blisters; 5) added text to clarify the time schedule of pharmacokinetic blood sampling and added reminder that actual times were to be collected in the electronic case report form (eCRF).