Date

2022-08-01

Protocol

Protocol changed

Item Changed

Inclusion criteria

Previous Version

• Male and female patients >18 years of age. • Biopsy-confirmed IgA Nephropathy (IgAN). (Patients with an eGFR of 30 to 45 mL/min/1.73m2 must have had a kidney biopsy performed within 36 months of the screening visit). • Stable and maximally tolerated dose of ACEI (Angiotensin-converting enzyme inhibitor) and/or ARB (Angiotensin receptor blocker) for at least 3 months prior to screening. Patients who are on a stable dose of SGLT2i may participate if treatment was initiated >3 months prior to screening. Patients who are unable to take an ACEI or ARB may participate if their overall management conforms with standards of care and other protocol requirements. • Screening urine protein/creatinine ratio (uPCR) >0.75 g/g or urine protein >1.0 g/day • eGFR >30 mL/min/1.73 m2, (for the exploratory cohort* only: eGFR 20- <30 mL/min/1.73 m2), calculated using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation. *The Exploratory cohort is up to 20 subjects with IgAN and an eGFR of 20 to 30 mL/min/1.73 m2. These subjects will also randomized with equal allocation (1:1) to sibeprenlimab or placebo in this cohort.

Next Version

• Subjects ? 18 years of age and of local legal consenting age at the time of signing the informed consent. • Subject has source-verified biopsy-confirmed IgAN. • Subject is on a stable and maximally tolerated dose of authorized ACEI and/or ARB (as per local SOC and applicable guidelines) for at least 3 months prior to screening. Furthermore, subjects who are on a stable dose of SGLT2i therapy for IgAN, in addition to ACEIs and/or ARBs, may participate in the trial if treatment was initiated at least 3 months prior to screening. Subjects who are unable to tolerate ACEI and/or ARB therapy may be eligible for participation in the trial if their overall management of IgAN, including blood pressure control, is as per local SOC and applicable guidelines. • Subject has screening urine protein/creatinine ratio (uPCR) ? 0.75 g/g or urine protein ? 1.0 g/day, as measured from 24-hour urine samples (mean of the two 24-hour urine samples collected up to 2 weeks apart at screening) and when the o subject is considered to be in steady-state. o Subject has eGFR ? 30 mL/min/1.73 m2, calculated using the CKD-EPI equation. o Subjects with an eGFR of 30 to 45 L/min/1.73m2 are required to have had a kidney biopsy performed within 36 months of the screening visit. o For the exploratory cohort only: subject has eGFR of 20 to 30 mL/min/1.73 m2, calculated using the CKD-EPI equation. o Serum creatinine assessments for the determination of eGFR should be taken when the subject 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, trimethoprim, cimetidine, pyrimethamine, fenofibrate, or creatine supplements), or changes in dietary protein intake. • Ability to provide written informed consent prior to initiation of any trial-specific procedures, and ability, in the opinion of the principal investigator, to comply with all the requirements of the trial.