A Phase 2/3 Trial of the Efficacy and Safety of Bardoxolone Methyl in Patients With Alport Syndrome - CARDINAL

Inclusion Criteria:

• Male and female patients 12 ≤ age ≤ 60 upon study consent;
• Diagnosis of Alport syndrome by genetic testing (documented mutation in a geneassociated with Alport syndrome, including COL4A3, COL4A4, or COL4A5) or histologicassessment using electron microscopy;
• Screening eGFR ≥ 30 and ≤ 90 mL/min/1.73 m2. The two eGFR values collected at Screen Aand Screen B visits used to determine eligibility must have a percent difference ≤ 25%;
• Albumin to creatinine ratio (ACR) ≤ 3500 mg/g at Screen B visit;
• If receiving an angiotensin-converting enzyme (ACE) inhibitor and/or an angiotensin IIreceptor blocker (ARB), the medications must remain the same for at least 6 weeksprior to the Screen A visit and during Screening. The dosage of ACE inhibitor and/orARB must also be stable for 2 weeks prior to the Screen A visit and remain the samethrough Day 1 (i.e., no change in dosage or medication). Patients not taking an ACEinhibitor and/or ARB because of a medical contraindication must have discontinuedtreatment at least 8 weeks prior to the Screen A visit;
• Adequate bone marrow reserve and organ function at the Screen A visit
• Able to swallow capsules;
• Willing and able to comply with scheduled visits, treatment plan, laboratory tests,and other study procedures;

Exclusion Criteria:

• Prior exposure to bardoxolone methyl;
• Ongoing chronic hemodialysis or peritoneal dialysis therapy;
• Renal transplant recipient;
• B-type natriuretic peptide (BNP) level > 200 pg/mL at Screen A visit;
• Uncontrolled diabetes (HbA1c > 11.0%) at Screen A visit;
• Acute dialysis or acute kidney injury within 12 weeks prior to Screen A visit orduring Screening;
• Serum albumin < 3 g/dL at Screen A visit;
• History of clinically significant left-sided heart disease and/or clinicallysignificant cardiac disease, including but not limited to any of the following:
• Uncontrolled systemic hypertension as evidenced by sitting systolic blood pressure (BP) > 160 mm Hg or sitting diastolic BP > 100 mm Hg at Screen A visit after a periodof rest;
• Systolic BP < 90 mm Hg at Screen A visit after a period of rest;
• History of malignancy within 5 years prior to Screen A visit, with the exception oflocalized skin or cervical carcinomas;
• Systemic immunosuppression for more than 2 weeks, cumulatively, within the 12 weeksprior to randomization or anticipated need for immunosuppression during the study;
• Untreated or uncontrolled active bacterial, fungal, or viral infection;
• Participation in other interventional clinical studies within 30 days prior to Day 1;
• Unwilling to practice acceptable methods of birth control (both males who havepartners of child-bearing potential and females of childbearing potential) duringScreening, while taking study drug, and for at least 30 days after the last dose ofstudy drug is ingested;
• Women who are pregnant or breastfeeding;
• Known hypersensitivity to any component of the study drug