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

RTA 402-C-1603

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.

2017-03-02

2020-10-06

2020-10-30

Completed

Early phase I

187

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

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2', 'PHASE3'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'TRIPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR']}}, 'enrollmentInfo': {'count': 187, 'type': 'ACTUAL'}}

2024-02-02