Date

2021-06-29

Protocol

Protocol changed

Item Changed

Inclusion criteria

Previous Version

Participants are eligible to be included in the study only if all of the following criteria apply: 1. Participant is a male or female greater than or equal 18 years of age at the time of signing the informed consent. Participant has biopsy-confirmed IgAN. Participant has medical records showing they have been on stable and maximally tolerated doses of either ACEI or ARB, as per SOC and applicable guidelines, for at least 3 months preceding screening. Participants should be on at least 50% of the maximum recommended dose of these agents to be considered as having adequate RAAS blockade. Participants who are unable to tolerate ACEI/ARB therapy may be eligible for participation in the study if their overall management of IgAN, including BP control, is as per SOC and applicable guidelines. Participant has screening uPCR greater than or equal to 0.75 g/g measured from a 24-hour urine (or an intended 24-hour urine sample) or 24-hour urine protein greater than or equal to 1.0 g/d, as measured from 24-hour urine collection (or an intended 24-hour urine sample). The proteinuria should be stable, defined as < 25% change when compared to values from greater than or equal to 3 months previously (if available). • If previous values are not available or if the change from a prior value is > 25%, a repeat measurement of proteinuria will be done after 15 days and the participant should fulfill the above proteinuria criteria to be eligible for randomization in the study. • The proteinuria should be assessed when the participant is considered to be in a steady state with no recent heavy exercise, fever, or other potential issues that could impact the result. Participant has eGFR greater than or equal to 45 mL/min/1.73 m2, calculated using the CKD-EPI formula. The eGFR should be stable, as defined by a < 25% change when compared to values from greater than or equal to 3 months previously (if available). • If previous values are not available or if the change from a prior value is > 25%, a repeat measurement of eGFR will be done after 15 days and the participant should fulfill the eGFR criteria to be eligible for randomization in the study. • The eGFR should be measured when the participant is considered to be in a steady state without recent changes in volume status, medications that could impact the result (eg, nonsteroidal anti-inflammatory drugs [NSAIDs], aminoglycosides, co-trimoxazole), or changes in dietary protein intake. 6.Participant’s serum Ig values must meet the following criteria: •IgG: greater than or equal 700 mg/dL •IgM: greater than or equal 40 mg/dL •IgA: greater than or equal 70 mg/dL 7.Female participants of childbearing potential must have a negative serum pregnancy test prior to the first dose. 8.Participant is willing to adhere to contraceptive requirements specified.

Next Version

1. Participant is a male or female ? 18 years of age at the time of signing the informed consent. 2. Participant has source-verified biopsy-confirmed IgAN. 3. Participant has medical records showing they have been on stable and maximally tolerated doses of either ACEI or ARB, as per local SOC and applicable guidelines, for at least 3 months preceding screening. Participants should optimally be on at least 50% of the maximum recommended dose of these agents; however, if a participant is on their maximally tolerated dose (and this is < 50% of the maximum recommended dose) and has been on this dose for at least 3 months, they may be enrolled. Participants who are unable to tolerate ACEI/ARB therapy may be eligible for participation in the study, if their overall management of IgAN, including BP control, is as per local SOC and applicable guidelines. 4. Participant has screening uPCR ? 0.75 g/g measured from a 24-hour urine sample (or an intended 24-hour urine sample) or 24-hour urine protein ? 1.0 g/d, as measured from 24-hour urine sample (or an intended 24-hour urine sample). The proteinuria should be assessed when the participant is considered to be in steady state with no recent heavy exercise, fever, or other potential issues that could impact the result. 5. Participant has eGFR ? 45 mL/min/1.73 m2, calculated using the CKD-EPI formula. Participants with eGFR ? 30 mL/min/1.73 m2 and < 45 mL/min/1.73 m2 may also undergo screening, if they have undergone a kidney biopsy within 12 months of the date of initial screening and do not have ? 50% tubulo-interstitial fibrosis (T2 if using MEST-C score) or crescents in ? 25% of glomeruli (C2 if using MEST-C score). The eGFR should be measured when the participant is considered to be in a steady state without recent changes in volume status, medications that could impact the result (eg, nonsteroidal anti-inflammatory drugs [NSAIDs], aminoglycosides, co-trimoxazole), or changes in dietary protein intake. 6. Participant’s serum Ig values must meet the following criteria: • IgG: ? 700 mg/dL • IgM: ? 37 mg/dL • c. IgA: ? 70 mg/dL