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