Study of Sparsentan in Patients With Primary Focal Segmental Glomerulosclerosis (FSGS)

This is a randomized, multicenter, double-blind, parallel, active-control study.
Approximately 300 patients aged 8 to 75 years (inclusive) will be enrolled in the study. The
study will be conducted in approximately 150 study centers, globally. The investigational
drug (sparsentan) is a dual acting angiotensin receptor blocker and endothelin receptor
antagonist. The active control is irbesartan. Patients who meet eligibility criteria will
require wash out from renin-angiotensin-aldosterone system (RAAS) blockers, if applicable
prior to their first dose of study drug.

Patients will be randomly assigned in a 1:1 ratio to receive either sparsentan or active
control (irbesartan).

Key Inclusion Criteria:

1. The patient or parent/legal guardian (as appropriate) is willing and able to provide
signed informed consent, and where required, the patient is willing to provide assent,
prior to any screening procedures.

2. The patient has biopsy-proven primary focal segmental glomerulosclerosis (FSGS) or
documentation of a genetic mutation in a podocyte protein associated with FSGS.

3. Sites within the US: The patient is male or female aged 8 to 75 years, inclusive.

Sites outside the US: The patient is male or female aged 18 to 75 years, inclusive.

4. The patient has a urine protein/creatinine (Up/C) ≥1.5 g/g at screening.

5. The patient has an eGFR ≥30 mL/min/1.73 m2 at screening.

6. Women of childbearing potential (WOCBP) must agree to the simultaneous use of 2
medically accepted methods of contraception from Day 1/Randomization until 90 days
after the last dose of study medication.

7. Males must be surgically sterile (more than 3 months post-vasectomy) or must agree to
the use of medically accepted methods of contraception that are considered highly
reliable from Day 1/Randomization until 90 days after the last dose of study
medication.

Key Exclusion Criteria:

1. The patient has FSGS secondary to another condition.

2. The patient has positive serological tests of primary or secondary glomerular injury
not consistent with a diagnosis of primary or genetic FSGS.

3. The patient has a history of type 1 diabetes mellitus, uncontrolled type 2 diabetes
mellitus.

4. The patient has undergone any organ transplantation, with the exception of corneal
transplants, or has received certain immunosuppressive medications.

5. The patient has a documented history of heart failure, coronary artery disease or
cerebrovascular disease.

6. The patient has significant liver disease.

7. The patient is positive at screening for the human immunodeficiency virus (HIV) or
markers indicating acute or chronic hepatitis B infection or hepatitis C infection.

8. The patient has a history of malignancy other than adequately treated basal cell or
squamous cell skin cancer or cervical carcinoma within the past 2 years.

9. The patient has disqualifying laboratory abnormalities during a screening.

10. The patient is >18 years of age with a body mass index (BMI) >40, or is ≤18 years of
age with a BMI in the 99th percentile plus 5 units at screening.

11. The patient has a history of alcohol or illicit drug use disorder.

12. The patient has a history of serious side effect or allergic response to any
angiotensin II antagonist or endothelin receptor antagonist.

13. The female patient is pregnant, plans to become pregnant during the course of the
study, or is breastfeeding.

14. The male patient plans to father a child during the course of the study.

15. The patient, in the opinion of the Investigator, is unable to adhere to the
requirements of the study, including the ability to swallow the study medication
capsules whole.