A Trial of Bardoxolone Methyl in Patients With ADPKD - FALCON (FALCON)
Autosomal Dominant Polycystic Kidney, ADPKD
About this trial
This is an interventional treatment trial for Autosomal Dominant Polycystic Kidney focused on measuring Bardoxolone Methyl, RTA 402, Autosomal Dominant Polycystic Kidney Disease, ADPKD
Eligibility Criteria
Inclusion Criteria:
- Male and female patients 12 ≤ age ≤ 70 upon study consent;
- Diagnosis of ADPKD by modified Pei-Ravine criteria: 1) at least 3 cysts per kidney by sonography or at least 5 cysts by CT or MRI with family history of ADPKD or 2) at least 10 cysts per kidney by any radiologic method and exclusion of other cystic kidney diseases if without family history;
Screening eGFR (average of Screen A and Screen B eGFR values) ≥ 30 to≤ 90 mL/min/1.73 m2 (18 to 55 years) or ≥ 30 to ≤ 44 mL/min/1.73 m2 (56 to 70 years):
1) Patients with either screening eGFR ≥ 60 to ≤ 90 mL/min/1.73 m2 or age 56 to 70 years, must have evidence of ADPKD progression (i.e., eGFR decline of ≥ 2.0 mL/min/1.73 m2 per year, based on historical eGFR data and medical monitor discretion); 2)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;
- Systolic blood pressure ≤ 140 mmHg and diastolic blood pressure ≤ 90 mmHg at Screen A visit after a period of rest.
Exclusion Criteria:
- History of administration of polycystic kidney disease-modifying agents (somatostatin analogues) within 3 months prior to the Screen A visit;
- B-type natriuretic peptide (BNP) level > 200 pg/mL at Screen A visit;
- Uncontrolled diabetes (HbA1c > 11.0%) at Screen A visit;
- Serum albumin < 3 g/dL at Screen A visit;
- History of intracranial aneurysms;
- Kidney or any other solid organ transplant recipient or a planned transplant during the study;
- Acute dialysis or acute kidney injury within 12 weeks prior to Screen A visit or during Screening;
- History of clinically significant left-sided heart disease and/or clinically significant cardiac disease;
- Systolic BP < 90 mm Hg at Screen A visit after a period of rest;
- BMI < 18.5 kg/m2 at the Screen A visit;
- History of malignancy within 5 years prior to Screen A visit, with the exception of localized skin or cervical carcinomas;
- Systemic immunosuppression for more than 2 weeks, cumulatively, within the 12 weeks prior to randomization or anticipated need for immunosuppression during the study;
- 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;
- Concomitant use of tolvaptan is excluded. Patients previously treated with tolvaptan must have discontinued drug for at least 3 months prior to Screen A visit
Sites / Locations
- University of Alabama at Birmingham
- Nephrology Associates PC
- Nephrology Consultants, LLC
- AKDHC
- Aventiv Research, Inc
- University of Arizona
- Rancho Research Institute
- California Institute Renal Research
- University of California, Los Angeles
- Keck USC/LAC
- Amicis Research Center
- Stanford University
- Apex Research of Riverside
- University of California San Francisco
- Western Nephrology
- University of Colorado Anschutz Medical Center
- Kidney Associates of Colorado
- Denver Nephrologist, PC
- Western Nephrology and Mineral Bone Disease, PC
- Yale University School of Medicine
- Pro-Care Research Center, Corp.
- University of Miami
- Discovery Medical Research Group
- Innovation Medical Research Center, Inc
- Volunteer Medical Research
- University of South Florida
- Florida Premier Research Institute, LLC
- Emory University
- Georgia Nephrology, LLC
- Boise Kidney & Hypertension, PLLC
- Boise Kidney & Hypertension, PLLC
- Northwestern University
- University of Chicago
- Loyola University Chicago
- University of Kansas Medical Center
- Cotton O'Neil Clinical Research Center
- Ascension Via Christi Research
- Kansas Nephrology Research Institute, LLC
- Renal Associates of Baton Rouge
- Northwest Louisiana Nephrology
- University of Maryland School of Medicine
- The Johns Hopkins University
- Tufts Medical Center
- Beth Israel Deaconess Medical Center
- KidneyCare and Tranplant Services of New England
- Renal and Transplant Associates of New England, PC
- Paragon Health PC d/b/a Nephrology Center PC
- Michigan Kidney Consultants
- Mayo Clinic
- Clinical Research Consultants, LLC
- Washington University in St. Louis
- KSOSN
- Nephrology Associates, P.C.
- Division of Kidney Diseases and Hypertension
- NYU Winthrop Hospital
- Mountain Kidney & Hypertension Associates
- Metrolina Nephrology Associates
- North Carolina Nephrology, P.A. 2nd Floor
- Brookview Hills Research Associates, LLC
- Cincinnati VA Medical Center
- University of Cincinnati College of Medicine
- Cleveland Clinic
- Remington-Davis Clinical Research
- Northeast Clinical Research Center
- University of Pennsylvania
- Children's Hospital of Philadelphia
- Columbia Nephrology Associates, PA
- Nephrology Associates, P.C.
- TTUHSC
- Arlington Nephrology, PA
- Research Management, Inc.
- Research Management, Inc.
- Liberty Research Center
- Renal Disease Research Institute
- Davita Clinical Research
- DaVita Med Center
- Clinical Advancement Center
- University of Vermont Medical Center
- University of Virginia
- Nephrology Associates of Northern Virginia, Inc.
- Swedish Medical Center
- Medical College of Wisconsin
- Milwaukee Nephrologists, SC
- Renal Research
- John Hunter Hospital
- Westmead Hospital
- Sunshine Coast University Hospital
- Royal Brisbane and Women's Hospital
- Royal Adelaide Hospital
- Monash Health
- Melbourne Health
- Melbourne Renal Research Group
- Fiona Stanley Hospital
- Nephrology, Cliniques U St-Luc
- Universitair Ziekenhuis Brussel (VUB)
- University Hospitals Leuven, Dept. of Nephrology, Dialysis and Renal Transplantation
- Chu Liege
- FN Brno
- Nephrology Dept., General Teaching Hospital
- IKEM
- University Hospital La Cavale Blanche
- Chu Grenoble Alpes
- Hospital Henri-Mondor AP-HP
- CHU de Nantes
- Hopital Necker, Universite Paris Descartes
- Universitätsklinikum Essen
- Medizinische Hochschule Hannover
- Klinikum rechts der Isar der TU München
- Renal Division, ASST Santi Paolo e Carlo
- Università di Modena e Reggio Emilia
- ICS Maugeri SpA SB
- Fondazione Policlinico Gemelli
- Hokkaido University Hospital
- Toranomon Hospital Kajigaya
- Japan Community Healthcare Organization Sendai Hospital
- Niigata University Medical & Dental Hospital
- Local Incorporated Administrative Agency Osaka City Hospital Organization Osaka City General Hospital
- Osaka City University Hospital
- Osaka University Hospital
- Toranomon Hospital
- Juntendo University Hospital
- Tokyo Women's Medical University Hospital
- Hospital Universitario de Badajoz
- Hospital Del Mar
- Fundacio Puigvert
- Hospital Universitario Reina Sofía
- Hospital Universitario Virgen de las Nieves
- Hospital Lucus Augusti
- Fundación Jiménez Díaz
- Hospital Universitario La Paz
- Hospital de Getafe
- Hospital Universitario Marques de Valdecilla
- Hospital Universitario Dr Peset
- North Bristol NHS Trust
- Manchester University NHS Foundation Trust
- Nottingham University Hospitals
- Morriston Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Placebo Comparator
Maximum bardoxolone methyl dose of 20 mg
Maximum bardoxolone methyl dose 30 mg
Placebo
Patients randomized to receive bardoxolone methyl with a baseline ACR less than or equal to 300 mg/g will be titrated to a maximum dose of 20 mg. Patients will begin once-daily dosing with bardoxolone methyl capsules at 5 mg and will dose escalate to 10 mg at Week 2 and 20 mg at Week 4. Patients will continue to receive study drug through Week 100, and will not receive study drug during a 12-week off-treatment period between Weeks 100 and 112.
Patients randomized to receive bardoxolone methyl with a baseline ACR greater than 300 mg/g will be titrated to a maximum dose of 30 mg. Patients will begin once-daily dosing with bardoxolone methyl capsules at 5 mg and will dose escalate to 10 mg at Week 2, 20 mg at Week 4 and 30 mg at Week 6. Patients will continue to receive study drug through Week 100, and will not receive study drug during a 12-week off-treatment period between Weeks 100 and 112.
Patients randomized to placebo will remain on placebo capsules throughout the study, undergoing sham titration. Patients will continue to receive placebo capsules through Week 100, and will not receive capsules during a 12-week off-treatment period between Weeks 100 and 112.