A Phase 2 Trial of the Safety and Efficacy of Bardoxolone Methyl in Patients With Rare Chronic Kidney Diseases - PHOENIX (PHOENIX)
IgA Nephropathy, CKD Associated With Type 1 Diabetes, Focal Segmental Glomerulosclerosis
About this trial
This is an interventional treatment trial for IgA Nephropathy focused on measuring IgA Nephropathy, CKD associated with type 1 diabetes, Focal segmental glomerulosclerosis, Autosomal dominant polycystic kidney disease, IgAN, FSGS, ADPKD, Bardoxolone methyl, CDDO-ME, RTA 402
Eligibility Criteria
Inclusion Criteria:
- Male and female patients 18 ≤ age ≤ 65 upon study consent;
- Screening eGFR (average of Screen A and Screen B eGFR values) ≥ 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) ≤ 2500 mg/g at Screen B visit;
- If receiving an angiotensin-converting enzyme (ACE) inhibitor and/or an angiotensin II receptor blocker (ARB), patients should be prescribed the maximally tolerated labeled daily dose (MTLDD) for at least 6 weeks prior to the Screen A visit;
- For patients enrolling in T1D Cohort: Diagnosis of type 1 diabetes confirmed by fasting C-peptide level. Diagnosis must have been made ≤ 35 years of age; and prescribed stable dose of insulin to maintain adequate glucose control for at least 6 months prior to the Screen A visit;
- For patients enrolling in IgAN Cohort: Biopsy-confirmed IgA nephropathy;
- For patients enrolling in FSGS Cohort: Biopsy-confirmed FSGS that is not due to known secondary causes including morbid obesity, decreased renal mass, viral infections, drug-induced nephrotoxicity, or prior history of vasculitis;
- For patients enrolling in ADPKD Cohort: Genetic confirmation of PKD1 mutation;
- Adequate bone marrow reserve and organ function at the Screen A visit as follows: Hematologic: Absolute neutrophil count > 1.5 x 109/L, platelets > 100 x 109/L, hemoglobin (Hgb) ≥ 9 g/dL; and Hepatic: Total bilirubin (TBL) ≤ 1.5 times the upper limit of normal (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 1.5 times ULN.
Exclusion Criteria:
- Kidney or any other solid organ transplant recipient or a planned transplant during the study;
- B-type natriuretic peptide (BNP) level > 200 pg/mL 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;
- Systemic immunosuppression for more than 2 weeks, cumulatively, within the 12 weeks prior to randomization or anticipated need for immunosuppression during the study;
- For patients enrolling in IgAN Cohort: Systemic manifestations of Henoch-Schonlein purpura within 1 year prior to Screen A visit; or have used belimumab, eculizumab, or rituximab within 6 months prior to Screen A visit;
- For patients enrolling in ADPKD Cohort: Receiving tolvaptan;
- Cerebrovascular event (stroke, transient ischemic attack) or aneurysm within 6 months prior to Screen A visit or during Screening;
- History of clinically significant left-sided heart disease and/or clinically significant cardiac disease;
- Uncontrolled systemic hypertension;
- Systolic BP < 90 mm Hg at Screen A visit after a period of rest;
- History of malignancy within 2 years prior to Screen A visit, with the exception of localized skin or cervical carcinomas;
- Uncontrolled diabetes (HbA1c > 10.0%) at Screen A visit;
- 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.
Sites / Locations
- University of Alabama Birmingham
- Phoenician Centers for Research & Innovation (PCRI)
- University of California Los Angeles
- Denver Nephrology
- Gulfcoast Endocrine and Diabetes Center
- South Florida Research Institute
- Coastal Nephrology Associates
- Kidney Care Augusta
- Boise Kidney & Hypertension, PLLC
- Boise Kidney & Hypertension, PLLC
- Research By Design
- University of Kansas Medical Center
- Four Rivers Clinical Research, Inc
- Northwest Louisiana Nephrology
- Tufts Medical Center - Division of Nephrology Tufts Medical Center
- Clinical Research Consultants, LLC
- Washington University School of Medicine
- Jacobi Medical Center
- Columbia University Medical Center - Nephrology
- Physician's East Endocrine Research
- Remington-Davis Clinical Research
- Northeast Clinical Research Center, LLC
- The Warren Alpert School of Brown University
- Nephrology Associates
- Research Management, Inc.
- Renal Disease Research Intitute
- Renal Associates, PA
- Advanced Clinical Research
- Mendez Center for Clinical Research LLC
- Larry Stonesifer, M.D.
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Experimental
Experimental
Experimental
Experimental
Bardoxolone Methyl - ADPKD
Bardoxolone Methyl - IgAN
Bardoxolone Methyl - T1D
Bardoxolone Methyl - FSGS
Participants with autosomal polycystic kidney disease (ADPKD) will receive bardoxolone methyl capsules at a starting dose of 5 mg and titrate up to a maximal dose of 20 mg (participants with UACR less than or equal to 300 mg/g) or 30 mg (participants with UACR greater than 300 mg/g) daily.
Participants with IgA nephropathy (IgAN) will receive bardoxolone methyl capsules at a starting dose of 5 mg and titrate up to a maximal dose of 20 mg (participants with UACR less than or equal to 300 mg/g) or 30 mg (participants with UACR greater than 300 mg/g) daily.
Participants with Type 1 diabetes (T1D) will receive bardoxolone methyl capsules at a starting dose of 5 mg and titrate up to a maximal dose of 20 mg (participants with UACR less than or equal to 300 mg/g) or 30 mg (participants with UACR greater than 300 mg/g) daily.
Participants with focal segmental glomerulosclerosis (FSGS) will receive bardoxolone methyl capsules at a starting dose of 5 mg and titrate up to a maximal dose of 20 mg (participants with UACR less than or equal to 300 mg/g) or 30 mg (participants with UACR greater than 300 mg/g) daily.