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

• Status: Completed
• Trial end date: 2020-10-30
• Target enrollment: 0
• Participant gender: All

Summary

This international, multi-center, Phase 2/3 trial will study the safety, tolerability, and efficacy of bardoxolone methyl in qualified patients with Alport syndrome. The Phase 2 portion of the trial will be open-label and enroll up to 30 patients. The Phase 3 portion of the trial will be double-blind, randomized, placebo-controlled and will enroll up to 180 patients.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Reata Pharmaceuticals, Inc.

Criteria

Inclusion Criteria:

• Male and female patients 12 ≤ age ≤ 60 upon study consent;

• Diagnosis of Alport syndrome by genetic testing (documented mutation in a gene associated with Alport syndrome, including COL4A3, COL4A4, or COL4A5) or histologic assessment using electron microscopy;

• Screening eGFR ≥ 30 and ≤ 90 mL/min/1.73 m2. The two eGFR values collected at Screen A and 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 II receptor blocker (ARB), the medications must remain the same for at least 6 weeks prior to the Screen A visit and during Screening. The dosage of ACE inhibitor and/or ARB must also be stable for 2 weeks prior to the Screen A visit and remain the same through Day 1 (i.e., no change in dosage or medication). Patients not taking an ACE inhibitor and/or ARB because of a medical contraindication must have discontinued treatment 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 or during Screening;

• Serum albumin < 3 g/dL at Screen A visit;

• History of clinically significant left-sided heart disease and/or clinically significant 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 period of 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 of localized skin or cervical carcinomas;

• Systemic immunosuppression for more than 2 weeks, cumulatively, within the 12 weeks prior 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 have partners of child-bearing potential and females of childbearing potential) during Screening, while taking study drug, and for at least 30 days after the last dose of study drug is ingested;

• Women who are pregnant or breastfeeding;

• Known hypersensitivity to any component of the study drug