Amendment 01: The protocol was modified to further define allowable or prohibited doses of corticosteroids that could be given for vasculitis and for reasons other than vasculitis, A statement was added to clarify that the protocol-defined induction regimens for cyclophosphamide were given as treatment targets but that they could be adjusted to account for renal insufficiency or reduced white blood cell counts as dictated by local standard of care practices, A subgroup analysis by duration of Intravenous (IV) corticosteroid pulse used for induction (1 day versus. >1 day) was added, The language regarding the recommended High dose corticosteroids (HDCS) tapering to reach the entry criteria of <10 mg/day was corrected from the previously written <10 mg/kg, The dose of Methotrexate (MTX) to be used in case of Azathioprine (AZA) toxicity was clarified to be a target dose, to allow for flexibility in individual practice. A minimum dose of MTX (no less than 10 mg/week) was also specified, to ensure participants were receiving a sufficient and relatively consistent therapy. This change also ensured the guidance given for MTX was consistent with that given for AZA

Amendment 02: The protocol was modified to include testing at Screening for human immunodeficiency virus (HIV) antibody, to expand Hepatitis B serology testing, and to exclude participants who tested positive according to the criteria specified, an alternative test, Hepatitis C virus (HCV) ribonucleic acid (RNA)-polymerase chain reaction (PCR) assay, was used to detect the presence of viral RNA, and hence confirm a current infection, The protocol was modified to exclude participants at baseline with abnormal liver function according to the criteria specified, A new section was added to clarify how participants care should be managed if a patient had a liver chemistry event during the study, Measurement of vital signs (temperature, sitting blood pressure [systolic and diastolic], and heart rate) were added to the procedures for all scheduled study visits and a 12 lead electrocardiogram (ECG) was added to the procedures for the Day 0 visit, Text was added to clarify that study agents were to be provided by the sponsor during the double-blind treatment phase, Within the definition of postmenopausal in Inclusion Criterion, “1 year without menses” was changed to “12 consecutive months with no menses without an alternative medical cause, Steroid use for vasculitis was modified to restrict the use of corticosteroids up to a maximum of 20 mg/day of prednisone (or equivalent) for a maximum of 1 week within the first 2 months of the double-blind treatment period, and at other times, to <10 mg/day, The investigator evaluation of Adverse events regarding causality was modified from a multi-choice assessment, Two new appendices were added to provide the questionnaires for the possible suicidality related history questionnaire (PSRHQ), The protocol was modified to include a Benefit and Risk Assessment, The Chapel Hill Consensus Conference (CHCC) definitions for Wegener’s granulomatosis and microscopic polyangiitis were updated.

Amendment 03: The protocol was modified to provide flexibility in timing of initiation of AZA maintenance therapy.The protocol was modified to allow alternative unlicensed RTX dose for induction (1 g every 2 weeks) in addition to the licensed dosing regimen (375 mg/m2/wk for 4 doses, The protocol was modified to provide flexibility in timing of baseline Birmingham Vasculitis Activity Score (BVAS) assessments – allowing 2 baseline assessments separated by at least 14 days, The absolute requirement to randomize within 14 days of confirmation of remission was removed and clarification was added that subjects could not be randomized until at least 6 weeks after initiation of induction therapy, Clarification was added regarding HDCS for induction and text provided guidance but allowed locally accepted practice. No subject should have received <10 mg for induction, The protocol was modified to allow some flexibility to Cyclophosphamide dosing regimens, The protocol was modified to allow the option to use MTX from the outset, as an alternative to AZA, if subject was a priori known to be AZA intolerant or had low/absent thiopurine methyltransferase (TPMT) activity. Exclusion of subjects with intolerance or contraindications to MTX (where this was being considered as an alternative to AZA), The protocol was modified to allow equal to/less than 10 mg prednisone daily during maintenance, Progressive multifocal leukoencephalopathy (PML) text was updated based on new information, The Benefit and Risk Assessment section was updated to reflect new and/or amended information in the protocol body.

Amendment 04: Protocol was modified to reflect a change by the sponsor to the strategic objectives for the evaluation of belimumab in ANCA-associated vasculitis (AAV). It was proposed that trial be changed from a Phase 3 to allow for an exploratory evaluation of belimumab in AAV only. The study design and schedule was modified in to clarify that the study would no longer be driven by the requirement to achieve at least 66 relapse events. The study was to complete and the primary analysis to be undertaken once 12 months had elapsed following enrolment of the last subject. The protocol was modified throughout such that (with exception of Belgium) participants completing the study no longer had the option to participate in a 6-month open-label extension following completion of the double-blind treatment phase, In the statistical sections of the protocol, the sample size considerations were modified to reflect the fact that approximately 100 participants were to be recruited, In the section “Dose, route of administration and schedule”, it was clarified that administration of belimumab or placebo should be over 1 hour, but not less than 1 hour for reasons of safety, The section on liver chemistry stopping and follow-up criteria, which described how participant care should be managed if a liver event occurred during the study, was updated with the most recent GSK-specified protocol for managing these events, The text on Progressive multifocal PML was updated to provide further guidance, The section “Reporting a pregnancy” was modified to provide scope for following up outcomes of a pregnancy as well as the status of mother and child, The section “Randomization procedure and assignment to treatment requirements” was modified to remove the requirement for participants to be randomized within 2 weeks of achieving remission, Protocol Appendix 12 was updated to reflect the change in study status to an exploratory trial and to reflect the changes in the main protocol.