Randomized, Double-Blind, Safety and Efficacy Study of RE-021 (Sparsentan) in Focal Segmental Glomerulosclerosis

Inclusion Criteria

• Biopsy-proven FSGS OR documentation of a genetic mutation in a podocyte protein associated with the disease.
• Urine protein/creatinine ratio (Up/C) at or above 1.0 g/g.
• Estimated glomerular filtration rate (eGFR) >30.
• Mean seated blood pressure (BP) >100/60 mmHg and /= 18 years of age. Mean seated BP for patients 90/60 mmHg and 8%), or non-fasting blood glucose >180 mg/dL at screening.
• Patients who have had any organ transplant.
• Patients with a requirement for any of the medications indicated on the list of Excluded Medications, with the exception of ACE and ARBs.
• Patients with a documented history of heart failure (NYHA Class II-IV), and / or previous hospitalization for heart failure or unexplained dyspnea, orthopnea, paroxysmal nocturnal dyspnea, ascites and peripheral edema. Patients with clinically significant cerebrovascular disease (transient ischemic attack or stroke) and/or coronary artery disease (hospitalization for myocardial infarction or unstable angina, new onset of angina with positive functional tests or coronary angiogram revealing stenosis, coronary revascularization procedure) within 6 months before screening.
• Patients with clinically significant cardiac conduction defects, including second or third degree atrioventricular block, left bundle branch block, sick sinus syndrome, atrial fibrillation, atrial flutter, an accessory bypass tract, or any arrhythmia requiring medication.
• Patients with jaundice, hepatitis, or known hepatobiliary disease (includes asymptomatic cholelithiasis); alanine aminotransferase and/or aspartate aminotransferase >2 times the upper limit of normal at Screening.
• Patients positive for human immunodeficiency virus (HIV), and markers indicating acute (positivity of at least one of the following: Hepatitis B surface antigen [HBsAg], Hepatitis B "e" antigen [HBeAg], Hepatitis B virus [HBV] DNA in blood or liver, Immunoglobulin M Hepatitis B core antibody) or chronic (HBsAg and/or HBeAg and/or Hepatitis B virus [HBV] DNA positivity) HBV infection, or hepatitis C virus (HCV) infection (reactive anti-HCV antibody and/or HCV RNA). Testing at screening is only required for patients >/= 18 years of age.
• History of malignancy other than adequately treated basal cell or squamous cell skin cancer within the past 5 years.
• Patients with hemodynamically significant valvular disease.
• Hematocrit (HCT) 5.5 mEq/L.
• Patients >18 years of age with Estimated Glomerular Filtration Rate (eGFR) ≥60 ml mL/min who have N-terminal prohormone of brain natriuretic peptide (NT-proBNP) ≥200 pg/mL (57.8 pmol/L). For patients >18 years of age with eGFR 18 years of age with eGFR 45 59.9 mL/min
• NT-proBNP = 200-299 pg/mL in patients >18 years of age with eGFR 45 59.9 mL/min, and abnormal ejection fraction (EF 18 years of age with eGFR 30.0 44.9 mL/min
• NT-proBNP = 200-399 pg/mL in patients >18 years of age with eGFR 30.0 44.9 mL/min, and abnormal ejection fraction (EF /= 18 years of age with body mass index (BMI) >40. Patients 12 consecutive months and for women on hormone replacement therapy, only with documented plasma follicle stimulating hormone level greater than 35 mIU/mL). Women using oral, implanted or injected contraceptive hormones, an intrauterine device, barrier methods (diaphragm, condoms, spermicidal) to prevent pregnancy, practicing abstinence or where the partner is sterile (e.g. vasectomy) As well as postmenopausal women who have fertilized eggs implanted are also considered WOCBP.
• Patients who have participated in another investigational drug study within 28 days prior to screening, or who will participate in another drug study during the course of this study.
• Prior exposure to Sparsentan, dual acting receptor antagonist (DARA), or PS433540.
• Patients who are unable to comply with the study procedures and assessments, including the ability swallow the study drug or control capsules.