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:

1. Age 18 years or older at screening
2. Biopsy-proven primary IgAN
3. Proteinuria of ≥1 g/day at screening
4. eGFR ≥30 mL/min/1.73 m2 at screening
5. 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)
6. Systolic BP ≤150 mmHg and diastolic BP ≤100 mmHg at screening
7. Willing to undergo change in ACEI and/or ARB and anti-hypertensive medications
8. Agree to contraception

Key Inclusion Criteria for the Open-Label Extension Period based on assessments at the Week 110 visit:

1. Completed participation in the double-blind period, including the Week 114 visit
2. Did not permanently discontinue study medication during the double-blind period
3. Agree to contraception

Key Inclusion Criteria for the OLE Sparsentan + SGLT2 Inhibitor Sub study:

1. 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
2. A urine protein excretion value of ≥0.3 g/day.
3. An eGFR of ≥25 mL/min/1.73m2
4. 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 Double-Blind Period:

1. IgAN secondary to another condition
2. Presence of cellular glomerular crescents in >25% of glomeruli on renal biopsy (if biopsy available within 6 months of screening)
3. Chronic kidney disease (CKD) in addition to IgAN
4. History of organ transplantation, with exception of corneal transplants
5. Require any prohibited medications
6. Treatment of systemic immunosuppressive medications (including corticosteroids) for >2 weeks within 3 months of screening
7. History of heart failure or previous hospitalization for heart failure or unexplained dyspnea, orthopnea, paroxysmal nocturnal dyspnea, ascites, and/or peripheral edema
8. Clinically significant cerebrovascular disease or coronary artery disease within 6 months of screening
9. Jaundice, hepatitis, or known hepatobiliary disease or elevations of transaminases (ALT/AST) >2 times upper limit of normal at screening
10. History of malignancy other than adequately treated basal cell or squamous cell skin cancer or cervical carcinoma within the past 2 years
11. Hematocrit value <27% (0.27 V/V) or hemoglobin value <9 g/dL (90 g/L) at Screening
12. Potassium >5.5 mEq/L (5.5 mmol/L) at Screening
13. History of alcohol of illicit drug use disorder
14. 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
15. For female: Pregnancy, or planning to become pregnant during the course of the study, or breastfeeding
16. Participation in a study of another investigational product within 28 days of screening

Key Exclusion Criteria for the Open-Label Extension Period based on assessments at the Week 110 and Week 114 visits:

1. Progression to end-stage renal disease (ESRD) requiring renal replacement therapy (RRT)
2. Development of any criteria for discontinuation of study medication or discontinuation from the study, between Week 110 and Week 114
3. Patient was unable to initiate, or developed contraindications to, treatment with RAAS inhibitors between Week 110 and Week 114
4. eGFR ≤20 mL/min/1.73 m2 at Week 110
5. Female patient is pregnant or breastfeeding

Key Exclusion Criteria for the OLE Sparsentan + SGLT2 Inhibitor Sub study:

1. Progressed to ESRD requiring RRT
2. Initiated or changed dose of a systemic immunosuppressive medication (including systemic steroids) within 12 weeks
3. Taking an SGLT2 inhibitor within 12 weeks