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

IgA Nephropathy Clinical Trial

— PHOENIX  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03366337
• Other study ID #: 402-C-1702
• Status: Completed
• Phase: Phase 2
• Start date: December 26, 2017
• Est. completion date: January 29, 2019

Study information

• Verified date: February 2024
• Source: Biogen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 103
• Est. completion date: January 29, 2019
• Est. primary completion date: January 2, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Autosomal Dominant Polycystic Kidney
• CKD Associated With Type 1 Diabetes
• Diabetes Mellitus, Type 1
• Focal Segmental Glomerulosclerosis
• Glomerulonephritis, IGA
• Glomerulosclerosis, Focal Segmental
• IgA Nephropathy
• Kidney Diseases
• Polycystic Kidney Diseases
• Polycystic Kidney, Autosomal Dominant
• Renal Insufficiency, Chronic

Intervention

Drug:
• Bardoxolone methyl capsules
Bardoxolone 5 mg capsules

Locations

Country	Name	City	State
United States	Kidney Care Augusta	Augusta	Georgia
United States	Research Management, Inc.	Austin	Texas
United States	Northeast Clinical Research Center, LLC	Bethlehem	Pennsylvania
United States	University of Alabama Birmingham	Birmingham	Alabama
United States	Tufts Medical Center - Division of Nephrology Tufts Medical Center	Boston	Massachusetts
United States	Jacobi Medical Center	Bronx	New York
United States	Boise Kidney & Hypertension, PLLC	Caldwell	Idaho
United States	Nephrology Associates	Chattanooga	Tennessee
United States	Gulfcoast Endocrine and Diabetes Center	Clearwater	Florida
United States	Remington-Davis Clinical Research	Columbus	Ohio
United States	Renal Disease Research Intitute	Dallas	Texas
United States	Denver Nephrology	Denver	Colorado
United States	Research By Design	Evergreen Park	Illinois
United States	Mendez Center for Clinical Research LLC	Fairfax Station	Virginia
United States	Larry Stonesifer, M.D.	Federal Way	Washington
United States	Physician's East Endocrine Research	Greenville	North Carolina
United States	Clinical Research Consultants, LLC	Kansas City	Missouri
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	South Florida Research Institute	Lauderdale Lakes	Florida
United States	University of California Los Angeles	Los Angeles	California
United States	Boise Kidney & Hypertension, PLLC	Meridian	Idaho
United States	Columbia University Medical Center - Nephrology	New York	New York
United States	Four Rivers Clinical Research, Inc	Paducah	Kentucky
United States	Phoenician Centers for Research & Innovation (PCRI)	Phoenix	Arizona
United States	Coastal Nephrology Associates	Port Charlotte	Florida
United States	The Warren Alpert School of Brown University	Providence	Rhode Island
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Renal Associates, PA	San Antonio	Texas
United States	Northwest Louisiana Nephrology	Shreveport	Louisiana
United States	Advanced Clinical Research	West Jordan	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Reata, a wholly owned subsidiary of Biogen

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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