A Trial of Bardoxolone Methyl in Patients With ADPKD - FALCON (FALCON)

A Phase 3 Trial of Bardoxolone Methyl in Patients With Autosomal Dominant Polycystic Kidney Disease

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.

Study Overview

• Status: Terminated
• Conditions: Autosomal Dominant Polycystic Kidney; ADPKD
• Intervention / Treatment: Drug: Bardoxolone methyl oral capsule; Drug: Placebo oral capsule

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.

• Study Type: Interventional
• Enrollment (Actual): 667
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Study Manager; Phone Number: +1 469-442-4754; Email: FALCON@reatapharma.com

Study Locations

• Australia
  • New South Wales
    • Gosford, New South Wales, Australia, 2250
      • Renal Research
    • New Lambton, New South Wales, Australia, 2305
      • John Hunter Hospital
    • Sydney, New South Wales, Australia, 2145
      • Westmead Hospital
  • Queensland
    • Birtinya, Queensland, Australia, 4575
      • Sunshine Coast University Hospital
    • Herston, Queensland, Australia, 4029
      • Royal Brisbane and Women's Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Health
    • Parkville, Victoria, Australia, 3050
      • Melbourne Health
    • Reservoir, Victoria, Australia, 3073
      • Melbourne Renal Research Group
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Fiona Stanley Hospital
• Belgium
  • Brussels, Belgium, 1200
    • Nephrology, Cliniques U St-Luc
  • Brussels, Belgium, B-1090
    • Universitair Ziekenhuis Brussel (VUB)
  • Leuven, Belgium, 3000
    • University Hospitals Leuven, Dept. of Nephrology, Dialysis and Renal Transplantation
  • Liège, Belgium, 4000
    • CHU Liege
• Czechia
  • Brno, Czechia, 62500
    • FN Brno
  • Prague, Czechia, 12808
    • Nephrology Dept., General Teaching Hospital
  • Praha, Czechia, 14021
    • IKEM
• France
  • Brest, France, 29200
    • University Hospital La Cavale Blanche
  • Grenoble, France, 38043
    • CHU Grenoble Alpes
  • Le Kremlin-Bicêtre, France, 94270
    • Hospital Henri-Mondor AP-HP
  • Nantes, France, 44093
    • CHU de Nantes
  • Paris, France, 75015
    • Hopital Necker, Universite Paris Descartes
• Germany
  • Essen, Germany, 45147
    • Universitatsklinikum Essen
  • Hanover, Germany, 30625
    • Medizinische Hochschule Hannover
  • München, Germany, 81675
    • Klinikum rechts der Isar der TU Munchen
• Italy
  • Milan, Italy, 20153
    • Renal Division, ASST Santi Paolo e Carlo
  • Modena, Italy, 41124
    • Università di Modena e Reggio Emilia
  • Pavia, Italy, 27100
    • ICS Maugeri SpA SB
  • Roma, Italy, 168
    • Fondazione Policlinico Gemelli
• Japan
  • Hokkaido, Japan, 060-8648
    • Hokkaido University Hospital
  • Kanagawa, Japan, 213-8587
    • Toranomon Hospital Kajigaya
  • Miyagi, Japan, 981-8501
    • Japan Community Healthcare Organization Sendai Hospital
  • Niigata, Japan, 951-8520
    • Niigata University Medical & Dental Hospital
  • Osaka, Japan, 565-0871
    • Osaka University Hospital
  • Osaka, Japan, 545-8586
    • Osaka City University Hospital
  • Osaka, Japan, 534-0021
    • Local Incorporated Administrative Agency Osaka City Hospital Organization Osaka City General Hospital
  • Tokyo, Japan, 162-8666
    • Tokyo Women's Medical University Hospital
  • Tokyo, Japan, 105-8470
    • Toranomon Hospital
  • Tokyo, Japan, 113-8431
    • Juntendo University Hospital
• Spain
  • Badajoz, Spain, 6070
    • Hospital Universitario de Badajoz
  • Barcelona, Spain, 8003
    • Hospital del Mar
  • Barcelona, Spain, 8025
    • Fundacio Puigvert
  • Córdoba, Spain, 14004
    • Hospital Universitario Reina Sofia
  • Granada, Spain, 18012
    • Hospital Universitario Virgen de las Nieves
  • Lugo, Spain, 27003
    • Hospital Lucus Augusti
  • Madrid, Spain, 28040
    • Fundacion Jimenez Diaz
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Madrid, Spain, 28905
    • Hospital de Getafe
  • Santander, Spain, 39008
    • Hospital Universitario Marques de Valdecilla
  • Valencia, Spain, 46017
    • Hospital Universitario Dr Peset
• United Kingdom
  • Bristol, United Kingdom, BS10 5NB
    • North Bristol NHS Trust
  • Manchester, United Kingdom, M13 9WL
    • Manchester University NHS Foundation Trust
  • Nottingham, United Kingdom, NG5 1PB
    • Nottingham University Hospitals
  • Swansea, United Kingdom, SA66NL
    • Morriston Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
    • Homewood, Alabama, United States, 35209
      • Nephrology Associates PC
    • Huntsville, Alabama, United States, 35805
      • Nephrology Consultants, LLC
  • Arizona
    • Glendale, Arizona, United States, 85306
      • AKDHC
    • Mesa, Arizona, United States, 85210
      • Aventiv Research, Inc
    • Tucson, Arizona, United States, 85719
      • University of Arizona
  • California
    • Downey, California, United States, 90242
      • Rancho Research Institute
    • La Mesa, California, United States, 91942
      • California Institute Renal Research
    • Los Angeles, California, United States, 90025
      • University of California, Los Angeles
    • Los Angeles, California, United States, 90033
      • Keck USC/LAC
    • Northridge, California, United States, 91324
      • Amicis Research Center
    • Palo Alto, California, United States, 94304
      • Stanford University
    • Riverside, California, United States, 92505
      • Apex Research of Riverside
    • San Francisco, California, United States, 94143
      • University of California San Francisco
  • Colorado
    • Arvada, Colorado, United States, 80002
      • Western Nephrology
    • Aurora, Colorado, United States, 80045
      • University of Colorado Anschutz Medical Center
    • Denver, Colorado, United States, 80210
      • Kidney Associates of Colorado
    • Denver, Colorado, United States, 80230
      • Denver Nephrologist, PC
    • Westminster, Colorado, United States, 80031
      • Western Nephrology and Mineral Bone Disease, PC
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University School of Medicine
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
    • Miami Gardens, Florida, United States, 33014
      • Pro-Care Research Center, Corp.
    • Ocala, Florida, United States, 34471
      • Discovery Medical Research Group
    • Palmetto Bay, Florida, United States, 33157
      • Innovation Medical Research Center, Inc
    • Port Charlotte, Florida, United States, 33952
      • Volunteer Medical Research
    • Tampa, Florida, United States, 33606
      • University of South Florida
    • Winter Park, Florida, United States, 32789
      • Florida Premier Research Institute, LLC
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
    • Lawrenceville, Georgia, United States, 30046
      • Georgia Nephrology, LLC
  • Idaho
    • Caldwell, Idaho, United States, 83605
      • Boise Kidney & Hypertension, PLLC
    • Meridian, Idaho, United States, 83642
      • Boise Kidney & Hypertension, PLLC
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60617
      • University of Chicago
    • Maywood, Illinois, United States, 60153
      • Loyola University Chicago
  • Kansas
    • Kansas City, Kansas, United States, 66224
      • University of Kansas Medical Center
    • Topeka, Kansas, United States, 66606
      • Cotton O'Neil Clinical Research Center
    • Wichita, Kansas, United States, 67214
      • Ascension Via Christi Research
    • Wichita, Kansas, United States, 67214
      • Kansas Nephrology Research Institute, LLC
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
      • Renal Associates of Baton Rouge
    • Shreveport, Louisiana, United States, 71101
      • Northwest Louisiana Nephrology
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland School of Medicine
    • Baltimore, Maryland, United States, 21287
      • The Johns Hopkins University
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
    • Springfield, Massachusetts, United States, 01107
      • Renal and Transplant Associates of New England, PC
    • Springfield, Massachusetts, United States, 01104
      • KidneyCare and Tranplant Services of New England
  • Michigan
    • Kalamazoo, Michigan, United States, 49007
      • Paragon Health PC d/b/a Nephrology Center PC
    • Pontiac, Michigan, United States, 48341
      • Michigan Kidney Consultants
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Clinical Research Consultants, LLC
    • Saint Louis, Missouri, United States, 63110
      • Washington University in St. Louis
  • Nevada
    • Las Vegas, Nevada, United States, 89129
      • KSOSN
  • New York
    • Flushing, New York, United States, 11355
      • Nephrology Associates, P.C.
    • Great Neck, New York, United States, 11021
      • Division of Kidney Diseases and Hypertension
    • Mineola, New York, United States, 11501
      • NYU Winthrop Hospital
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Mountain Kidney & Hypertension Associates
    • Charlotte, North Carolina, United States, 28204
      • Metrolina Nephrology Associates
    • Raleigh, North Carolina, United States, 27609
      • North Carolina Nephrology, P.A. 2nd Floor
    • Winston-Salem, North Carolina, United States, 27103
      • Brookview Hills Research Associates, LLC
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati College of Medicine
    • Cincinnati, Ohio, United States, 45220
      • Cincinnati VA Medical Center
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Columbus, Ohio, United States, 43215
      • Remington-Davis Clinical Research
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18017
      • Northeast Clinical Research Center
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
    • Philadelphia, Pennsylvania, United States, 19014
      • University of Pennsylvania
  • South Carolina
    • Columbia, South Carolina, United States, 29203
      • Columbia Nephrology Associates, PA
  • Tennessee
    • Nashville, Tennessee, United States, 37205
      • Nephrology Associates, P.C.
  • Texas
    • Amarillo, Texas, United States, 79106
      • TTUHSC
    • Arlington, Texas, United States, 76015
      • Arlington Nephrology, PA
    • Austin, Texas, United States, 78758
      • Research Management, Inc.
    • Austin, Texas, United States, 78751
      • Research Management, Inc.
    • Dallas, Texas, United States, 75235
      • Renal Disease Research Institute
    • Dallas, Texas, United States, 75230
      • Liberty Research Center
    • El Paso, Texas, United States, 79925
      • Davita Clinical Research
    • Houston, Texas, United States, 77004
      • DaVita Med Center
    • San Antonio, Texas, United States, 78215
      • Clinical Advancement Center
  • Vermont
    • Burlington, Vermont, United States, 05401
      • University of Vermont Medical Center
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia
    • Fairfax, Virginia, United States, 22033
      • Nephrology Associates of Northern Virginia, Inc.
  • Washington
    • Seattle, Washington, United States, 98052
      • Swedish Medical Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin
    • Wauwatosa, Wisconsin, United States, 53226
      • Milwaukee Nephrologists, SC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 70 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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):

  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 or B visit after a period of rest.

Exclusion Criteria:

• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Maximum bardoxolone methyl dose of 20 mg; 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.	Drug: Bardoxolone methyl oral capsule; Bardoxolone methyl capsules dose escalated from 5 mg to a maximum of 20 or 30 mg, depending on baseline proteinuria status.; Other Names: RTA 402
Experimental: Maximum bardoxolone methyl dose 30 mg; 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.	Drug: Bardoxolone methyl oral capsule; Bardoxolone methyl capsules dose escalated from 5 mg to a maximum of 20 or 30 mg, depending on baseline proteinuria status.; Other Names: RTA 402
Placebo Comparator: Placebo; 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.	Drug: Placebo oral capsule; Capsule containing an inert placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in eGFR from baseline (108 weeks)	To assess the off-treatment change from baseline in estimated glomerular filtration rate (eGFR) at Week 108 for patients receiving active drug, compared to patients receiving placebo.	108 weeks
Count of reported adverse events	Safety and tolerability will be assessed by counting adverse events, as defined by the Medical Dictionary for Regulatory Activities (MedDRA)	112 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in eGFR from baseline (100 weeks)	To assess the off-treatment change from baseline in eGFR at Week 100, for patients receiving active drug, compared to patients receiving placebo.	100 weeks

Collaborators and Investigators

• Sponsor: Reata, a wholly owned subsidiary of Biogen

Study record dates

Study Major Dates

• Study Start (Actual): May 29, 2019
• Primary Completion (Actual): August 8, 2023
• Study Completion (Actual): August 8, 2023

Study Registration Dates

• First Submitted: April 12, 2019
• First Submitted That Met QC Criteria: April 16, 2019
• First Posted (Actual): April 17, 2019

Study Record Updates

• Last Update Posted (Actual): April 12, 2024
• Last Update Submitted That Met QC Criteria: April 11, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: ADPKD; Bardoxolone Methyl; Autosomal Dominant Polycystic Kidney Disease; RTA 402
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Congenital Abnormalities; Genetic Diseases, Inborn; Joint Diseases; Musculoskeletal Diseases; Muscular Diseases; Musculoskeletal Abnormalities; Abnormalities, Multiple; Kidney Diseases, Cystic; Ciliopathies; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Polycystic Kidney Diseases; Polycystic Kidney, Autosomal Dominant; Arthrogryposis
• Other Study ID Numbers: 402-C-1808

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
• product manufactured in and exported from the U.S.: Yes