A Trial of Bardoxolone Methyl in Patients With ADPKD - FALCON
- Conditions
- ADPKDAutosomal Dominant Polycystic Kidney
- Interventions
- Drug: Placebo oral capsule
- Registration Number
- NCT03918447
- Lead Sponsor
- Reata, a wholly owned subsidiary of Biogen
- Brief Summary
This international, multi-center, randomized, double-blind, placebo-controlled Phase 3 trial will study the safety, tolerability, and efficacy of bardoxolone methyl in qualified patients with ADPKD. Approximately 850 patients will be enrolled.
- Detailed Description
This international, multi-center, randomized, double-blind, placebo-controlled Phase 3 trial will study the safety, tolerability, and efficacy of bardoxolone methyl in qualified patients with ADPKD.
Patients will be randomized 1:1 to either bardoxolone methyl or placebo. Patients receiving bardoxolone methyl will start with once-daily dosing at 5 mg and will dose-escalate to 10 mg at Week 2, to 20 mg at Week 4, and then to 30 mg at Week 6 (only if baseline ACR \>300 mg/g) unless contraindicated clinically and approved by the medical monitor. Dose de-escalation is permitted during the study if indicated clinically, and subsequent dose re-escalation is also permitted to meet the dosing objective of the highest tolerated dose.
All patients in the study will follow the same visit and assessment schedule. Patients will continue to receive study drug or placebo through Week 100 and will not receive study drug or placebo during a 12-week off-treatment period between Weeks 100 and 112.
Study Sponsor, originally Reata Pharmaceuticals, Inc., is now Reata Pharmaceuticals, Inc., a wholly owned subsidiary of Biogen.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 667
-
Male and female patients 12 ≤ age ≤ 70 upon study consent;
-
Diagnosis of ADPKD by modified Pei-Ravine criteria (for adults 18≤ age ≤70 years): 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 (12 to 55 years) or ≥ 30 to ≤ 44 mL/min/1.73 m2 (56 to 70 years):
- 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 or B visit after a period of rest.
- History of administration of polycystic kidney disease-modifying agents (somatostatin analogues) within 2 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 2 months prior to Screen A visit
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Maximum bardoxolone methyl dose of 20 mg Bardoxolone methyl oral capsule 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. Maximum bardoxolone methyl dose 30 mg Bardoxolone methyl oral capsule 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. Placebo Placebo oral capsule 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.
- Primary Outcome Measures
Name Time Method Off-treatment Period: Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 108 Baseline, Week 108 Estimated Glomerular filtration rate (eGFR) is a measure of kidney function assessed through blood/serum. eGFR was measured in milliliters per minute per 1.73 meters square (mL/min/1.73 m\^2). Higher eGFRs represent better/improved kidney function. Lower eGFRs represent poorer/decreased kidney function. Negative change from baseline in eGFR indicates worsened kidney function.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs From first dose of the study drug up to end of follow-up (up to Week 112) AE:any untoward medical occurrence in a participant regardless of its causal relationship to study drug.AE can be any unfavorable \& unintended sign,symptom/disease temporally associated with use of study drug,whether considered to be study-drug related/not.This includes clinically significant abnormal laboratory test result,any newly occurring events/previous conditions that have increased in severity/frequency since administration of study drug. SAE:any AE that at any dose results in death,life-threatening,requires hospitalization/prolongation of existing hospitalisation,substantial disruption of ability to conduct normal life functions,congenital anomaly or is an important medical event. AEs \& SAEs that occurred during treatment and within 30 days after last dose were considered TE.
- Secondary Outcome Measures
Name Time Method Treatment Period: Change From Baseline in eGFR at Week 100 Baseline, Week 100 eGFR is a measure of kidney function assessed through blood/serum. eGFR was measured in mL/min/1.73 m\^2. Higher eGFRs represent better/improved kidney function. Lower eGFRs represent poorer/decreased kidney function. A negative change from baseline in eGFR indicates worsened kidney function.
Related Research Topics
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Trial Locations
- Locations (134)
Florida Premier Research Institute, LLC
🇺🇸Winter Park, Florida, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Remington-Davis Clinical Research
🇺🇸Columbus, Ohio, United States
DaVita Med Center
🇺🇸Houston, Texas, United States
The Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
University of Cincinnati College of Medicine
🇺🇸Cincinnati, Ohio, United States
University of Miami
🇺🇸Miami, Florida, United States
University of Arizona
🇺🇸Tucson, Arizona, United States
University of California, Los Angeles
🇺🇸Los Angeles, California, United States
University of Virginia
🇺🇸Charlottesville, Virginia, United States
Swedish Medical Center
🇺🇸Seattle, Washington, United States
Monash Health
🇦🇺Clayton, Victoria, Australia
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Kidney Associates of Colorado
🇺🇸Denver, Colorado, United States
Denver Nephrologist, PC
🇺🇸Denver, Colorado, United States
Nephrology Associates, P.C.
🇺🇸Nashville, Tennessee, United States
Clinical Advancement Center
🇺🇸San Antonio, Texas, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
University of Colorado Anschutz Medical Center
🇺🇸Aurora, Colorado, United States
University of South Florida
🇺🇸Tampa, Florida, United States
NYU Winthrop Hospital
🇺🇸Mineola, New York, United States
North Carolina Nephrology, P.A. 2nd Floor
🇺🇸Raleigh, North Carolina, United States
Cincinnati VA Medical Center
🇺🇸Cincinnati, Ohio, United States
Keck USC/LAC
🇺🇸Los Angeles, California, United States
Amicis Research Center
🇺🇸Northridge, California, United States
Nephrology Consultants, LLC
🇺🇸Huntsville, Alabama, United States
Stanford University
🇺🇸Palo Alto, California, United States
Western Nephrology
🇺🇸Arvada, Colorado, United States
University of California San Francisco
🇺🇸San Francisco, California, United States
Volunteer Medical Research
🇺🇸Port Charlotte, Florida, United States
Discovery Medical Research Group
🇺🇸Ocala, Florida, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Loyola University Chicago
🇺🇸Maywood, Illinois, United States
Cotton O'Neil Clinical Research Center
🇺🇸Topeka, Kansas, United States
Northwest Louisiana Nephrology
🇺🇸Shreveport, Louisiana, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
Division of Kidney Diseases and Hypertension
🇺🇸Great Neck, New York, United States
Paragon Health PC d/b/a Nephrology Center PC
🇺🇸Kalamazoo, Michigan, United States
Renal and Transplant Associates of New England, PC
🇺🇸Springfield, Massachusetts, United States
Arlington Nephrology, PA
🇺🇸Arlington, Texas, United States
TTUHSC
🇺🇸Amarillo, Texas, United States
John Hunter Hospital
🇦🇺New Lambton, New South Wales, Australia
Melbourne Renal Research Group
🇦🇺Reservoir, Victoria, Australia
Fiona Stanley Hospital
🇦🇺Murdoch, Western Australia, Australia
Nephrology, Cliniques U St-Luc
🇧🇪Brussels, Belgium
Chu Liege
🇧🇪Liège, Belgium
Universitair Ziekenhuis Brussel (VUB)
🇧🇪Brussels, Belgium
IKEM
🇨🇿Praha, Czechia
FN Brno
🇨🇿Brno, Czechia
University Hospital La Cavale Blanche
🇫🇷Brest, France
Hopital Necker, Universite Paris Descartes
🇫🇷Paris, France
Chu Grenoble Alpes
🇫🇷Grenoble, France
Universitätsklinikum Essen
🇩🇪Essen, Germany
CHU de Nantes
🇫🇷Nantes, France
Klinikum rechts der Isar der TU München
🇩🇪München, Germany
Università di Modena e Reggio Emilia
🇮🇹Modena, Italy
ICS Maugeri SpA SB
🇮🇹Pavia, Italy
Renal Division, ASST Santi Paolo e Carlo
🇮🇹Milan, Italy
Hokkaido University Hospital
🇯🇵Hokkaido, Japan
Fondazione Policlinico Gemelli
🇮🇹Roma, Italy
Japan Community Healthcare Organization Sendai Hospital
🇯🇵Miyagi, Japan
Toranomon Hospital Kajigaya
🇯🇵Kanagawa, Japan
Niigata University Medical & Dental Hospital
🇯🇵Niigata, Japan
Osaka City University Hospital
🇯🇵Osaka, Japan
Osaka University Hospital
🇯🇵Osaka, Japan
Hospital Universitario de Badajoz
🇪🇸Badajoz, Spain
Toranomon Hospital
🇯🇵Tokyo, Japan
Juntendo University Hospital
🇯🇵Tokyo, Japan
Hospital Del Mar
🇪🇸Barcelona, Spain
Tokyo Women's Medical University Hospital
🇯🇵Tokyo, Japan
Fundacio Puigvert
🇪🇸Barcelona, Spain
Hospital Lucus Augusti
🇪🇸Lugo, Spain
Hospital Universitario Reina Sofía
🇪🇸Córdoba, Spain
Hospital Universitario Virgen de las Nieves
🇪🇸Granada, Spain
Hospital de Getafe
🇪🇸Madrid, Spain
Fundación Jiménez Díaz
🇪🇸Madrid, Spain
Hospital Universitario Dr Peset
🇪🇸Valencia, Spain
Hospital Universitario Marques de Valdecilla
🇪🇸Santander, Spain
Morriston Hospital
🇬🇧Swansea, United Kingdom
North Bristol NHS Trust
🇬🇧Bristol, United Kingdom
Western Nephrology and Mineral Bone Disease, PC
🇺🇸Westminster, Colorado, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Hospital Henri-Mondor AP-HP
🇫🇷Le Kremlin-Bicêtre, France
Nephrology Associates PC
🇺🇸Homewood, Alabama, United States
AKDHC
🇺🇸Glendale, Arizona, United States
Rancho Research Institute
🇺🇸Downey, California, United States
Aventiv Research, Inc
🇺🇸Mesa, Arizona, United States
California Institute Renal Research
🇺🇸La Mesa, California, United States
Apex Research of Riverside
🇺🇸Riverside, California, United States
Pro-Care Research Center, Corp.
🇺🇸Miami Gardens, Florida, United States
Innovation Medical Research Center, Inc
🇺🇸Palmetto Bay, Florida, United States
Georgia Nephrology, LLC
🇺🇸Lawrenceville, Georgia, United States
Boise Kidney & Hypertension, PLLC
🇺🇸Meridian, Idaho, United States
Ascension Via Christi Research
🇺🇸Wichita, Kansas, United States
Kansas Nephrology Research Institute, LLC
🇺🇸Wichita, Kansas, United States
Renal Associates of Baton Rouge
🇺🇸Baton Rouge, Louisiana, United States
University of Maryland School of Medicine
🇺🇸Baltimore, Maryland, United States
KidneyCare and Tranplant Services of New England
🇺🇸Springfield, Massachusetts, United States
Michigan Kidney Consultants
🇺🇸Pontiac, Michigan, United States
KSOSN
🇺🇸Las Vegas, Nevada, United States
Washington University in St. Louis
🇺🇸Saint Louis, Missouri, United States
Mountain Kidney & Hypertension Associates
🇺🇸Asheville, North Carolina, United States
Metrolina Nephrology Associates
🇺🇸Charlotte, North Carolina, United States
Northeast Clinical Research Center
🇺🇸Bethlehem, Pennsylvania, United States
Research Management, Inc.
🇺🇸Austin, Texas, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Columbia Nephrology Associates, PA
🇺🇸Columbia, South Carolina, United States
Liberty Research Center
🇺🇸Dallas, Texas, United States
Renal Disease Research Institute
🇺🇸Dallas, Texas, United States
Davita Clinical Research
🇺🇸El Paso, Texas, United States
Nephrology Associates of Northern Virginia, Inc.
🇺🇸Fairfax, Virginia, United States
University of Vermont Medical Center
🇺🇸Burlington, Vermont, United States
Milwaukee Nephrologists, SC
🇺🇸Wauwatosa, Wisconsin, United States
Renal Research
🇦🇺Gosford, New South Wales, Australia
Westmead Hospital
🇦🇺Sydney, New South Wales, Australia
Royal Brisbane and Women's Hospital
🇦🇺Herston, Queensland, Australia
Sunshine Coast University Hospital
🇦🇺Birtinya, Queensland, Australia
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
Melbourne Health
🇦🇺Parkville, Victoria, Australia
University Hospitals Leuven, Dept. of Nephrology, Dialysis and Renal Transplantation
🇧🇪Leuven, Belgium
Nephrology Dept., General Teaching Hospital
🇨🇿Prague, Czechia
Medizinische Hochschule Hannover
🇩🇪Hanover, Germany
Local Incorporated Administrative Agency Osaka City Hospital Organization Osaka City General Hospital
🇯🇵Osaka, Japan
Nottingham University Hospitals
🇬🇧Nottingham, United Kingdom
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Manchester University NHS Foundation Trust
🇬🇧Manchester, United Kingdom
Brookview Hills Research Associates, LLC
🇺🇸Winston-Salem, North Carolina, United States
Yale University School of Medicine
🇺🇸New Haven, Connecticut, United States
Clinical Research Consultants, LLC
🇺🇸Kansas City, Missouri, United States
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States