Alport Syndrome
Conditions
Interventions
Drug: Bardoxolone Methyl Bardoxolone methyl dose escalated from 5 mg to a maximum of 20 or 30 mg, depending on baseline proteinuria status. Dosing period is up to 2 years.
Drug: Placebo Oral Capsule
Sponsors
Reata Pharmaceuticals, Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male and female patients from the age of 12 to 70 upon study consent 2. 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 3. Screening eGFR (average of Screen A and Screen B eGFR values) is from 30 to 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 of 25% and under 4. Albumin to creatinine ratio (ACR) is 3500 mg/g and under at Screen B visit. Up to 50% of patients in the Phase 2 cohort and approximately 40% of patients enrolled in the Phase 3 cohort can have ACR of 301 to 3500 mg/g. Once enrollment of these patients is complete, the ACR inclusion criterion is 300 mg/g and under. 5. Patients receiving an angiotensin-converting enzyme (ACE) inhibitor and/or an angiotensin II receptor blocker (ARB) should be receiving the maximally tolerated labeled daily dose for at least 6 weeks prior to the Screen A visit. The dosage of ACE inhibitor and/or ARB should remain the same throughout the remainder of the study. Patients not currently taking an ACE inhibitor and/or ARB because they are not indicated or because of a medical contraindication may be eligible provided the patient has not taken an ACE inhibitor and/or ARB at least 8 weeks prior to the Screen A visit. 6. Adequate bone marrow reserve and organ function at the Screen A visit as follows: a. Hematologic: Absolute neutrophil count > 1500/microliter, platelets > 100000/microliter, hemoglobin of 9 g/dL and over b. Hepatic: Total bilirubin (TBL) of 1.5X the upper limit of normal (ULN) and under, ALT and AST of 1.5X ULN and under 7. Able to swallow capsules 8. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures 9. Evidence of a personally signed and dated informed consent document
Exclusion criteria
Exclusion criteria: 1. Prior exposure to bardoxolone methyl 2. Ongoing chronic hemodialysis or peritoneal dialysis therapy 3. Renal transplant recipient 4. B-type natriuretic peptide (BNP) level > 200 pg/mL at Screen A visit 5. Uncontrolled diabetes (HbA1c > 11.0%) at Screen A visit 6. Acute dialysis or acute kidney injury within 12 weeks prior to Screen A visit or during Screening 7. Serum albumin < 3 g/dL at Screen A visit 8. History of clinically significant left-sided heart disease and/or clinically significant cardiac disease 9. 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 10. Systolic BP < 90 mm Hg at Screen A visit after a period of rest 11. History of malignancy within 5 years prior to Screen A visit, with the exception of localized skin or cervical carcinomas 12. Systemic immunosuppression for more than 2 weeks, cumulatively, within the 12 weeks prior to randomization or anticipated need for immunosuppression during the study 13. Untreated or uncontrolled active bacterial, fungal, or viral infection 14. Participation in other interventional clinical studies within 30 days prior to Day 1 15. 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 16. Women who are pregnant or breastfeeding 17. Known hypersensitivity to any component of the study drug
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The change from baseline in eGFR in bardoxolone methyl-treated patients relative to placebo at Week 48 | — |
Secondary
| Measure | Time frame |
|---|---|
| The change from baseline in eGFR in bardoxolone methyl-treated patients relative to placebo at Week 52 following a 4-week drug treatment withdrawal period. | — |
Countries
Japan,North America,Australia,Europe
Contacts
Public ContactYukiko Hagihara
Labcorp Development Japan K.K. Clinical Development Services
Outcome results
None listed