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

Phase 2

Completed

• Conditions: Autosomal Dominant Polycystic Kidney; IgA Nephropathy; CKD Associated With Type 1 Diabetes; Focal Segmental Glomerulosclerosis
• Interventions: Drug: Bardoxolone methyl capsules

• Registration Number: NCT03366337
• Lead Sponsor: Reata, a wholly owned subsidiary of Biogen

Brief Summary

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.

Detailed Description

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

Study Timeline

• Study First Submitted: 2017-12-04
• Study First Submitted QC: 2017-12-04
• Study First Posted: 2017-12-08
• Study Start: 2017-12-26
• Primary Completion: 2019-01-02
• Study Completion: 2019-01-29
• Disposition First Submitted: 2019-12-20
• Disposition First Submitted QC: 2019-12-20
• Disposition First Posted: 2019-12-24
• Results First Submitted: 2021-12-17
• Results First Submitted QC: 2021-12-17
• Results First Posted: 2022-01-18
• Status Verified: 2024-02
• Last Update Submitted: 2024-02-01
• Last Update Posted: 2024-02-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 103

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Bardoxolone Methyl - IgAN	Bardoxolone methyl capsules	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.
Bardoxolone Methyl - FSGS	Bardoxolone methyl capsules	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.
Bardoxolone Methyl - ADPKD	Bardoxolone methyl capsules	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.
Bardoxolone Methyl - T1D	Bardoxolone methyl capsules	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.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 12	12 weeks after participant receives the first dose	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.

Trial Locations

Locations (29)

Tufts Medical Center - Division of Nephrology Tufts Medical Center; 🇺🇸 Boston, Massachusetts, United States

Gulfcoast Endocrine and Diabetes Center; 🇺🇸 Clearwater, Florida, United States

Advanced Clinical Research; 🇺🇸 West Jordan, Utah, United States

Coastal Nephrology Associates; 🇺🇸 Port Charlotte, Florida, United States

Kidney Care Augusta; 🇺🇸 Augusta, Georgia, United States

Four Rivers Clinical Research, Inc; 🇺🇸 Paducah, Kentucky, United States

Remington-Davis Clinical Research; 🇺🇸 Columbus, Ohio, United States

Physician's East Endocrine Research; 🇺🇸 Greenville, North Carolina, United States

Renal Disease Research Intitute; 🇺🇸 Dallas, Texas, United States

Northwest Louisiana Nephrology; 🇺🇸 Shreveport, Louisiana, United States

Boise Kidney & Hypertension, PLLC; 🇺🇸 Meridian, Idaho, United States

Phoenician Centers for Research & Innovation (PCRI); 🇺🇸 Phoenix, Arizona, United States

Renal Associates, PA; 🇺🇸 San Antonio, Texas, United States

University of Alabama Birmingham; 🇺🇸 Birmingham, Alabama, United States

Denver Nephrology; 🇺🇸 Denver, Colorado, United States

Research Management, Inc.; 🇺🇸 Austin, Texas, United States

University of California Los Angeles; 🇺🇸 Los Angeles, California, United States

South Florida Research Institute; 🇺🇸 Lauderdale Lakes, Florida, United States

Research By Design; 🇺🇸 Evergreen Park, Illinois, United States

Columbia University Medical Center - Nephrology; 🇺🇸 New York, New York, United States

The Warren Alpert School of Brown University; 🇺🇸 Providence, Rhode Island, United States

Northeast Clinical Research Center, LLC; 🇺🇸 Bethlehem, Pennsylvania, United States

Nephrology Associates; 🇺🇸 Chattanooga, Tennessee, United States

Larry Stonesifer, M.D.; 🇺🇸 Federal Way, Washington, United States

Mendez Center for Clinical Research LLC; 🇺🇸 Fairfax Station, Virginia, United States

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States

Clinical Research Consultants, LLC; 🇺🇸 Kansas City, Missouri, United States

Jacobi Medical Center; 🇺🇸 Bronx, New York, United States

University of Kansas Medical Center; 🇺🇸 Kansas City, Kansas, United States