A Phase 2 Trial of the Safety and Efficacy of Bardoxolone Methyl in Patients With Rare Chronic Kidney Diseases - PHOENIX (PHOENIX)

A Phase 2 Trial of the Safety and Efficacy of Bardoxolone Methyl in Patients With Rare Chronic Kidney Diseases

This multi-center, open-label Phase 2 trial will study the safety, tolerability, and efficacy of bardoxolone methyl in qualified patients with the following rare chronic kidney diseases (CKD): CKD associated with type 1 diabetes (T1D), IgA nephropathy (IgAN), focal segmental glomerulosclerosis (FSGS), and autosomal dominant polycystic kidney disease (ADPKD). Patients will be enrolled in disease specific cohorts within the trial, and effectiveness of bardoxolone methyl in treating CKD will be assessed separately by cohort for each rare CKD.

All patients in the study will follow the same visit and assessment schedule. Following randomization on Day 1, patients will be scheduled to be assessed during treatment at Weeks 1, 2, 4, 6, 8, and 12, and by telephone contact on Days 3, 10, 21, 31, 38, and 45. Patients will also be scheduled to be assessed at an in-person follow-up visit at Week 16, four weeks after the end of treatment.

Study Overview

• Status: Completed
• Conditions: Focal Segmental Glomerulosclerosis; IgA Nephropathy; Autosomal Dominant Polycystic Kidney; CKD Associated With Type 1 Diabetes
• Intervention / Treatment: Drug: Bardoxolone methyl capsules

Detailed Description

Study Sponsor, originally Reata Pharmaceuticals, Inc., is now Reata Pharmaceuticals, Inc., a wholly owned subsidiary of Biogen.

• Study Type: Interventional
• Enrollment (Actual): 103
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama Birmingham
  • Arizona
    • Phoenix, Arizona, United States, 85021
      • Phoenician Centers for Research & Innovation (PCRI)
  • California
    • Los Angeles, California, United States, 90095
      • University of California Los Angeles
  • Colorado
    • Denver, Colorado, United States, 80230
      • Denver Nephrology
  • Florida
    • Clearwater, Florida, United States, 33756
      • Gulfcoast Endocrine and Diabetes Center
    • Lauderdale Lakes, Florida, United States, 33313
      • South Florida Research Institute
    • Port Charlotte, Florida, United States, 33952
      • Coastal Nephrology Associates
  • Georgia
    • Augusta, Georgia, United States, 30909
      • Kidney Care Augusta
  • Idaho
    • Caldwell, Idaho, United States, 83605
      • Boise Kidney & Hypertension, PLLC
    • Meridian, Idaho, United States, 83642
      • Boise Kidney & Hypertension, PLLC
  • Illinois
    • Evergreen Park, Illinois, United States, 60805
      • Research by Design
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Kentucky
    • Paducah, Kentucky, United States, 42003
      • Four Rivers Clinical Research, Inc
  • Louisiana
    • Shreveport, Louisiana, United States, 71101
      • Northwest Louisiana Nephrology
  • Massachusetts
    • Boston, Massachusetts, United States, 02110
      • Tufts Medical Center - Division of Nephrology Tufts Medical Center
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Clinical Research Consultants, LLC
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New York
    • Bronx, New York, United States, 10461
      • Jacobi Medical Center
    • New York, New York, United States, 10032
      • Columbia University Medical Center - Nephrology
  • North Carolina
    • Greenville, North Carolina, United States, 27834
      • Physician's East Endocrine Research
  • Ohio
    • Columbus, Ohio, United States, 43215
      • Remington-Davis Clinical Research
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18017
      • Northeast Clinical Research Center, LLC
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • The Warren Alpert School of Brown University
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Nephrology Associates
  • Texas
    • Austin, Texas, United States, 78751
      • Research Management, Inc.
    • Dallas, Texas, United States, 75235
      • Renal Disease Research Intitute
    • San Antonio, Texas, United States, 78215
      • Renal Associates, PA
  • Utah
    • West Jordan, Utah, United States, 84088
      • Advanced Clinical Research
  • Virginia
    • Fairfax Station, Virginia, United States, 22039
      • Mendez Center for Clinical Research LLC
  • Washington
    • Federal Way, Washington, United States, 98003
      • Larry Stonesifer, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bardoxolone Methyl - ADPKD; 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.	Drug: Bardoxolone methyl capsules; Bardoxolone 5 mg capsules; Other Names: RTA 402
Experimental: Bardoxolone Methyl - IgAN; 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.	Drug: Bardoxolone methyl capsules; Bardoxolone 5 mg capsules; Other Names: RTA 402
Experimental: Bardoxolone Methyl - T1D; 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.	Drug: Bardoxolone methyl capsules; Bardoxolone 5 mg capsules; Other Names: RTA 402
Experimental: Bardoxolone Methyl - FSGS; 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.	Drug: Bardoxolone methyl capsules; Bardoxolone 5 mg capsules; Other Names: RTA 402

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 12	To assess the change in eGFR from baseline to week 12. eGFR is a measure of kidney function assessed through blood/serum. Higher eGFRs represent better/improved kidney function. Lower eGFRs represent poorer/decreased kidney function.	12 weeks after participant receives the first dose

Collaborators and Investigators

• Sponsor: Biogen

Publications and helpful links

Helpful Links

• Link to the PHOENIX trial website, which contains information about the trial and participating centers

Study record dates

Study Major Dates

• Study Start (Actual): December 26, 2017
• Primary Completion (Actual): January 2, 2019
• Study Completion (Actual): January 29, 2019

Study Registration Dates

• First Submitted: December 4, 2017
• First Submitted That Met QC Criteria: December 4, 2017
• First Posted (Actual): December 8, 2017

Study Record Updates

• Last Update Posted (Actual): June 3, 2025
• Last Update Submitted That Met QC Criteria: May 22, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: ADPKD; FSGS; IgA Nephropathy; RTA 402; Bardoxolone methyl; Autosomal dominant polycystic kidney disease; IgAN; Focal segmental glomerulosclerosis; CDDO-ME; CKD associated with type 1 diabetes
• Additional Relevant MeSH Terms: Ciliopathies; Urogenital Diseases; Endocrine System Diseases; Pathologic Processes; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Genetic Diseases, Inborn; Metabolic Diseases; Autoimmune Diseases; Immune System Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Renal Insufficiency; Congenital Abnormalities; Abnormalities, Multiple; Glomerulonephritis; Nephritis; Kidney Diseases, Cystic; Diabetes Mellitus, Type 1; Kidney Diseases; Renal Insufficiency, Chronic; Glomerulonephritis, IGA; Polycystic Kidney Diseases; Polycystic Kidney, Autosomal Dominant; Glomerulosclerosis, Focal Segmental
• Other Study ID Numbers: 402-C-1702

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No