• SUSAR reporting section was modified to permit delegation of SUSAR reporting responsibilities by the CI. • Clinical trial identifier was added. • Study short title was added

• Changes to study design. • Addition of text relating to the recruitment of non-English speakers. • Amendment to text relating to the unblinding process. • Changes relating to the cellular immunology aspects of the protocol. • Clarification of level of training required for administration of the study drug. • Clarification of text relating to the treatment of reaction occurring during study drug administration. • Clarification of text relating to exposure to the study drug during pregnancy. • Correction made to SAE definition • Clarification of time points for obtaining research blood samples. • Several minor administrative changes made to text for clarity

• Change to the timing of completion of discharge questionnaires. • Removal of GOSEPeds at discharge • Amendment to text relating to one of the exploratory objectives and clarification of outcome measures to achieve this objective • Change to and addition of new study time point for research blood sampling • Removal of 'region' as a stratification factor for randomization • Amendment of information relating to documentation of participant Study ID • Clarification on the process of questionnaire completion • Amendment to text relating to blood processing for clarity • Amendment to the Study Flow Chart and Schedule of Study Procedures • Several minor amendments made to text for clarity.

• Clarification of time window for administration of first dose of the study drug. • Clarification of exclusion criterion relating to IgA deficiency. • Clarification to text relating to research sample type being collected. • Clarification of text relating to withdrawal of participant from study treatment. • Clarification of the role of DSMC relating to review of data quality. • Amendment to the risk of anaphylaxis following general anaesthesia. • Minor amendment made to schedule of study procedures to clarify timing of research blood sampling.

• Addition of mandatory full blood count check 24-48 hours following the 2nd dose of the study drug as a risk mitigation measure to monitor for signs of haemolysis with IVIG treatment. • Amendment to age ranges that define which of the neuropsychology assessments will be done.

• Page 36: Time point ‘T6 Around 12 months post randomisation’ was incorrectly documented as ‘T5 Around 12 months post randomisation’. This has been corrected to read T6. • Page 42: Section 9.5 Concomitant Medications - The sentence ‘Participants should not be enrolled if they are still being actively followed up in another study that involves an IMP’ has been removed, consistent with similar changes in version 3.0 of the protocol, as per the decision at the previous DSMC meeting.

• Clarification on reporting of serious adverse events beyond the 6 months post randomisation time point. • Clarification of what age to use for ex premature infants when assessing eligibility. • Modification of the exclusion criterion relating to co-enrolment to other IMP trials to make this in line with the changes made in the last amendment. • Clarification of the process of obtaining consent from 16 year old participants beyond the initial hospital admission period. • Clarification of the processes around the time of randomization. • Clarification on the role of the PI in unblinding. • Clarification of the age groups for the different cognitive scales for participants in the IgNiTE trial. • Clarification on the process of obtaining the safety FBC result for participant’s transferred to a non-IgNiTE participating hospital before the test is due. • Amendment to the description of the study time points to provide clarity. • Clarification on the procedure for recording adverse events. • Clarification of the process of reporting serious adverse events and follow up of these where ongoing at the end of the participant’s time in the study. • Minor change to the wording of the exclusion criterion relating to recruitment within the study time window to improve clarity. • For consistency of terminology, we have used 4instead of SAEs judged to be related to the IMP throughout the protocol. • Update to the versions of the WPPSI and WISC to be used. Note that REC approval to update the WPPSI to version 4 was obtained in SA5 but this change was not effected in the protocol. • Correction to the spelling of ‘Behaviors’ in the text ‘Adaptive Behaviors Assessment System’. • For consistency and where appropriate, we have replaced the term ‘IMP’ with ‘study drug’. • Addition of a window around the T2+7d time point. • Extension of the 4-6 week post discharge from acute care time point by 2 weeks to allow an additional time for completion of study questionnaires.

• Extension of the time window for administration of the first dose of study drug. • Clarification on the starting point for calculating the time window for administering the first dose of study treatment. • Deletion of the exclusion criterion relating to the time window for administering the first dose of study drug . • Increase in the number of recruiting sites to 40. • Inclusion of additional clinical endpoints 6. Modification of text relating to an inclusion criterion to provide clarity. • Addition of text explaining the rationale for inclusion of clinically improving patients to the IgNiTE trial. • Correction to the protocol version number for the last substantial amendment in the amendment history section of the protocol. • Clarification of patients to be recorded on the screening log.

• Update to details of key trial contacts. • Reference to UK GDPR added to the protocol alongside the reference to the Data Protection Act. • Removal of endpoints which cannot be derived from the data collected. • Removal of Biobank approach and consent in section 8.8. • Updates to section numbering where subsections have been deleted due to the changes made to study design. • Update to version number and date throughout. • Removal of information on blood processing related to exploratory endpoints. • Minor change to text for clarity. • Update the statisticians on the trial. • Update the statistical analysis section due to the early termination. • Addition of text relating to early trial termination. • Post study completion clarification of study activities at the T2 +7d time point, allowing this to be completed by telephone should it be required and clarification that AESIs and SAEs can be collected at this timepoint. • At the time that funding was withdrawn, the NIHR continued to fund completion of study activities for all enrolled participants unless they had withdrawn consent. They completed the trial activities as planned