A Study of the Effect and Safety of Sparsentan in the Treatment of Patients With IgA Nephropathy

Key Inclusion Criteria for the Double-Blind Period: * Age 18 years or older at screening * Biopsy-proven primary IgAN * Proteinuria of ≥1 g/day at screening * eGFR ≥30 mL/min/1.73 m2 at screening * Currently on stable dose of ACEI and/or ARB therapy, for at least 12 weeks prior to screening (maximum tolerated dose and at least one-half of the maximum labeled dose) * Systolic BP ≤150 mmHg and diastolic BP ≤100 mmHg at screening * Willing to undergo change in ACEI and/or ARB and anti-hypertensive medications * Agree to contraception Key Exclusion Criteria for the Double-Blind Period: * IgAN secondary to another condition * Presence of cellular glomerular crescents in \>25% of glomeruli on renal biopsy (if biopsy available within 6 months of screening) * Chronic kidney disease (CKD) in addition to IgAN * History of organ transplantation, with exception of corneal transplants * Require any prohibited medications * Treatment of systemic immunosuppressive medications (including corticosteroids) for \>2 weeks within 3 months of screening * History of heart failure or previous hospitalization for heart failure or unexplained dyspnea, orthopnea, paroxysmal nocturnal dyspnea, ascites, and/or peripheral edema * Clinically significant cerebrovascular disease or coronary artery disease within 6 months of screening * Jaundice, hepatitis, or known hepatobiliary disease or elevations of transaminases (ALT/AST) \>2 times upper limit of normal at screening * History of malignancy other than adequately treated basal cell or squamous cell skin cancer or cervical carcinoma within the past 2 years * Hematocrit value \<27% (0.27 V/V) or hemoglobin value \<9 g/dL (90 g/L) at Screening * Potassium \>5.5 mEq/L (5.5 mmol/L) at Screening * History of alcohol of illicit drug use disorder * History of serious side effect or allergic response to any angiotensin II antagonist or endothelin receptor antagonist, including sparsentan or irbesartan, or has a hypersensitivity to any of the excipients in the study medications * For female: Pregnancy, or planning to become pregnant during the course of the study, or breastfeeding * Participation in a study of another investigational product within 28 days of screening Key Inclusion Criteria for the Open-Label Extension Period based on assessments at the Week 110 visit: * Completed participation in the double-blind period, including the Week 114 visit * Did not permanently discontinue study medication during the double-blind period * Agree to contraception Key Exclusion Criteria for the Open-Label Extension Period based on assessments at the Week 110 and Week 114 visits: * Progression to end-stage renal disease (ESRD) requiring renal replacement therapy (RRT) * Development of any criteria for discontinuation of study medication or discontinuation from the study, between Week 110 and Week 114 * Patient was unable to initiate, or developed contraindications to, treatment with RAAS inhibitors between Week 110 and Week 114 * eGFR ≤20 mL/min/1.73 m2 at Week 110 * Female patient is pregnant or breastfeeding Key Inclusion Criteria for the OLE Sparsentan + SGLT2 Inhibitor Sub study: * Participating in the open-label extension and is willing and able to provide signed informed consent for participation in the open-label extension period Sub study * A urine protein excretion value of ≥0.3 g/day. * An eGFR of ≥25 mL/min/1.73m2 * On a stable dose of sparsentan for ≥8 weeks in the open-label extension period that is the maximum tolerated dose. Key Exclusion Criteria for the OLE Sparsentan + SGLT2 Inhibitor Sub study: * Progressed to ESRD requiring RRT * Initiated or changed dose of a systemic immunosuppressive medication (including systemic steroids) within 12 weeks * Taking an SGLT2 inhibitor within 12 weeks