A Trial of Bardoxolone Methyl in Patients With ADPKD - FALCON

NCT ID: NCT03918447

Last Updated: 2025-06-03

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 667 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-29
• Study Completion Date: 2023-08-08

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.

Conditions

Autosomal Dominant Polycystic Kidney; ADPKD

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Bardoxolone methyl oral capsule

Intervention Type: DRUG

Bardoxolone methyl capsules dose escalated from 5 mg to a maximum of 20 or 30 mg, depending on baseline proteinuria status.

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.

Group Type: EXPERIMENTAL

Bardoxolone methyl oral capsule

Intervention Type: DRUG

Bardoxolone methyl capsules dose escalated from 5 mg to a maximum of 20 or 30 mg, depending on baseline proteinuria status.

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.

Group Type: PLACEBO_COMPARATOR

Placebo oral capsule

Intervention Type: DRUG

Capsule containing an inert placebo

Interventions

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.

Intervention Type: DRUG

Placebo oral capsule

Capsule containing an inert placebo

Intervention Type: DRUG

Other Intervention Names

RTA 402

Eligibility Criteria

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

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Biogen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Nephrology Associates PC

Homewood, Alabama, United States

Nephrology Consultants, LLC

Huntsville, Alabama, United States

AKDHC

Glendale, Arizona, United States

Aventiv Research, Inc

Mesa, Arizona, United States

University of Arizona

Tucson, Arizona, United States

Rancho Research Institute

Downey, California, United States

California Institute Renal Research

La Mesa, California, United States

University of California, Los Angeles

Los Angeles, California, United States

Keck USC/LAC

Los Angeles, California, United States

Amicis Research Center

Northridge, California, United States

Stanford University

Palo Alto, California, United States

Apex Research of Riverside

Riverside, California, United States

University of California San Francisco

San Francisco, California, United States

Western Nephrology

Arvada, Colorado, United States

University of Colorado Anschutz Medical Center

Aurora, Colorado, United States

Kidney Associates of Colorado

Denver, Colorado, United States

Denver Nephrologist, PC

Denver, Colorado, United States

Western Nephrology and Mineral Bone Disease, PC

Westminster, Colorado, United States

Yale University School of Medicine

New Haven, Connecticut, United States

University of Miami

Miami, Florida, United States

Pro-Care Research Center, Corp.

Miami Gardens, Florida, United States

Discovery Medical Research Group

Ocala, Florida, United States

Innovation Medical Research Center, Inc

Palmetto Bay, Florida, United States

Volunteer Medical Research

Port Charlotte, Florida, United States

University of South Florida

Tampa, Florida, United States

Florida Premier Research Institute, LLC

Winter Park, Florida, United States

Emory University

Atlanta, Georgia, United States

Georgia Nephrology, LLC

Lawrenceville, Georgia, United States

Boise Kidney & Hypertension, PLLC

Caldwell, Idaho, United States

Boise Kidney & Hypertension, PLLC

Meridian, Idaho, United States

Northwestern University

Chicago, Illinois, United States

University of Chicago

Chicago, Illinois, United States

Loyola University Chicago

Maywood, Illinois, United States

University of Kansas Medical Center

Kansas City, Kansas, United States

Cotton O'Neil Clinical Research Center

Topeka, Kansas, 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

Northwest Louisiana Nephrology

Shreveport, Louisiana, United States

University of Maryland School of Medicine

Baltimore, Maryland, United States

The Johns Hopkins University

Baltimore, Maryland, United States

Tufts Medical Center

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

KidneyCare and Tranplant Services of New England

Springfield, Massachusetts, United States

Renal and Transplant Associates of New England, PC

Springfield, Massachusetts, United States

Paragon Health PC d/b/a Nephrology Center PC

Kalamazoo, Michigan, United States

Michigan Kidney Consultants

Pontiac, Michigan, United States

Mayo Clinic

Rochester, Minnesota, United States

Clinical Research Consultants, LLC

Kansas City, Missouri, United States

Washington University in St. Louis

St Louis, Missouri, United States

KSOSN

Las Vegas, Nevada, United States

Nephrology Associates, P.C.

Flushing, New York, United States

Division of Kidney Diseases and Hypertension

Great Neck, New York, United States

NYU Winthrop Hospital

Mineola, New York, United States

Mountain Kidney & Hypertension Associates

Asheville, North Carolina, United States

Metrolina Nephrology Associates

Charlotte, North Carolina, United States

North Carolina Nephrology, P.A. 2nd Floor

Raleigh, North Carolina, United States

Brookview Hills Research Associates, LLC

Winston-Salem, North Carolina, United States

Cincinnati VA Medical Center

Cincinnati, Ohio, United States

University of Cincinnati College of Medicine

Cincinnati, Ohio, United States

Cleveland Clinic

Cleveland, Ohio, United States

Remington-Davis Clinical Research

Columbus, Ohio, United States

Northeast Clinical Research Center

Bethlehem, Pennsylvania, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Columbia Nephrology Associates, PA

Columbia, South Carolina, United States

Nephrology Associates, P.C.

Nashville, Tennessee, United States

TTUHSC

Amarillo, Texas, United States

Arlington Nephrology, PA

Arlington, Texas, United States

Research Management, Inc.

Austin, Texas, United States

Research Management, Inc.

Austin, Texas, 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

DaVita Med Center

Houston, Texas, United States

Clinical Advancement Center

San Antonio, Texas, United States

University of Vermont Medical Center

Burlington, Vermont, United States

University of Virginia

Charlottesville, Virginia, United States

Nephrology Associates of Northern Virginia, Inc.

Fairfax, Virginia, United States

Swedish Medical Center

Seattle, Washington, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Milwaukee Nephrologists, SC

Wauwatosa, Wisconsin, United States

Renal Research

Gosford, New South Wales, Australia

John Hunter Hospital

New Lambton, New South Wales, Australia

Westmead Hospital

Sydney, New South Wales, Australia

Sunshine Coast University Hospital

Birtinya, Queensland, Australia

Royal Brisbane and Women's Hospital

Herston, Queensland, Australia

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Monash Health

Clayton, Victoria, Australia

Melbourne Health

Parkville, Victoria, Australia

Melbourne Renal Research Group

Reservoir, Victoria, Australia

Fiona Stanley Hospital

Murdoch, Western Australia, Australia

Nephrology, Cliniques U St-Luc

Brussels, , Belgium

Universitair Ziekenhuis Brussel (VUB)

Brussels, , Belgium

University Hospitals Leuven, Dept. of Nephrology, Dialysis and Renal Transplantation

Leuven, , Belgium

Chu Liege

Liège, , Belgium

FN Brno

Brno, , Czechia

Nephrology Dept., General Teaching Hospital

Prague, , Czechia

IKEM

Prague, , Czechia

University Hospital La Cavale Blanche

Brest, , France

Chu Grenoble Alpes

Grenoble, , France

Hospital Henri-Mondor AP-HP

Le Kremlin-Bicêtre, , France

CHU de Nantes

Nantes, , France

Hopital Necker, Universite Paris Descartes

Paris, , France

Universitätsklinikum Essen

Essen, , Germany

Medizinische Hochschule Hannover

Hanover, , Germany

Klinikum rechts der Isar der TU München

München, , Germany

Renal Division, ASST Santi Paolo e Carlo

Milan, , Italy

Università di Modena e Reggio Emilia

Modena, , Italy

ICS Maugeri SpA SB

Pavia, , Italy

Fondazione Policlinico Gemelli

Roma, , Italy

Hokkaido University Hospital

Hokkaido, , Japan

Toranomon Hospital Kajigaya

Kanagawa, , Japan

Japan Community Healthcare Organization Sendai Hospital

Miyagi, , Japan

Niigata University Medical & Dental Hospital

Niigata, , Japan

Local Incorporated Administrative Agency Osaka City Hospital Organization Osaka City General Hospital

Osaka, , Japan

Osaka City University Hospital

Osaka, , Japan

Osaka University Hospital

Osaka, , Japan

Toranomon Hospital

Tokyo, , Japan

Juntendo University Hospital

Tokyo, , Japan

Tokyo Women's Medical University Hospital

Tokyo, , Japan

Hospital Universitario de Badajoz

Badajoz, , Spain

Hospital Del Mar

Barcelona, , Spain

Fundacio Puigvert

Barcelona, , Spain

Hospital Universitario Reina Sofía

Córdoba, , Spain

Hospital Universitario Virgen de las Nieves

Granada, , Spain

Hospital Lucus Augusti

Lugo, , Spain

Fundación Jiménez Díaz

Madrid, , Spain

Hospital Universitario La Paz

Madrid, , Spain

Hospital de Getafe

Madrid, , Spain

Hospital Universitario Marques de Valdecilla

Santander, , Spain

Hospital Universitario Dr Peset

Valencia, , Spain

North Bristol NHS Trust

Bristol, , United Kingdom

Manchester University NHS Foundation Trust

Manchester, , United Kingdom

Nottingham University Hospitals

Nottingham, , United Kingdom

Morriston Hospital

Swansea, , United Kingdom

Countries

United States; Australia; Belgium; Czechia; France; Germany; Italy; Japan; Spain; United Kingdom

References

St Pierre K, Cashmore BA, Bolignano D, Zoccali C, Ruospo M, Craig JC, Strippoli GF, Mallett AJ, Green SC, Tunnicliffe DJ. Interventions for preventing the progression of autosomal dominant polycystic kidney disease. Cochrane Database Syst Rev. 2024 Oct 2;10(10):CD010294. doi: 10.1002/14651858.CD010294.pub3.

Reference Type: DERIVED

PMID: 39356039 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

402-C-1808

Identifier Type: -

Identifier Source: org_study_id