NCT03918447

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.

Trial Health

68
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network
Enrollment
667

participants targeted

Target at P75+ for phase_3

Timeline
Completed

Started May 2019

Typical duration for phase_3

Geographic Reach
10 countries

137 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 12, 2019

Completed
5 days until next milestone

First Posted

Study publicly available on registry

April 17, 2019

Completed
1 month until next milestone

Study Start

First participant enrolled

May 29, 2019

Completed
4.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 8, 2023

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 8, 2023

Completed
10 months until next milestone

Results Posted

Study results publicly available

June 11, 2024

Completed
Last Updated

June 3, 2025

Status Verified

May 1, 2025

Enrollment Period

4.2 years

First QC Date

April 12, 2019

Results QC Date

April 26, 2024

Last Update Submit

May 22, 2025

Conditions

Keywords

Bardoxolone MethylRTA 402Autosomal Dominant Polycystic Kidney DiseaseADPKD

Outcome Measures

Primary Outcomes (2)

  • Off-treatment Period: Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at 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.

    Baseline, Week 108

  • Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs

    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.

    From first dose of the study drug up to end of follow-up (up to Week 112)

Secondary Outcomes (1)

  • Treatment Period: Change From Baseline in eGFR at Week 100

    Baseline, Week 100

Study Arms (3)

Maximum bardoxolone methyl dose of 20 mg

EXPERIMENTAL

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

Maximum bardoxolone methyl dose 30 mg

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

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

Also known as: RTA 402
Maximum bardoxolone methyl dose 30 mgMaximum bardoxolone methyl dose of 20 mg

Capsule containing an inert placebo

Placebo

Eligibility Criteria

Age12 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Male and female patients 12 ≤ age ≤ 70 upon study consent;
  • 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.

You may not qualify if:

  • 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;
  • +2 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (137)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Nephrology Associates PC

Homewood, Alabama, 35209, United States

Location

Nephrology Consultants, LLC

Huntsville, Alabama, 35805, United States

Location

AKDHC

Glendale, Arizona, 85306, United States

Location

Aventiv Research, Inc

Mesa, Arizona, 85210, United States

Location

University of Arizona

Tucson, Arizona, 85719, United States

Location

Rancho Research Institute

Downey, California, 90242, United States

Location

California Institute Renal Research

La Mesa, California, 91942, United States

Location

University of California, Los Angeles

Los Angeles, California, 90025, United States

Location

Keck USC/LAC

Los Angeles, California, 90033, United States

Location

Amicis Research Center

Northridge, California, 91324, United States

Location

Stanford University

Palo Alto, California, 94304, United States

Location

Apex Research of Riverside

Riverside, California, 92505, United States

Location

University of California San Francisco

San Francisco, California, 94143, United States

Location

Western Nephrology

Arvada, Colorado, 80002, United States

Location

University of Colorado Anschutz Medical Center

Aurora, Colorado, 80045, United States

Location

Kidney Associates of Colorado

Denver, Colorado, 80210, United States

Location

Denver Nephrologist, PC

Denver, Colorado, 80230, United States

Location

Western Nephrology and Mineral Bone Disease, PC

Westminster, Colorado, 80031, United States

Location

Yale University School of Medicine

New Haven, Connecticut, 06520, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Pro-Care Research Center, Corp.

Miami Gardens, Florida, 33014, United States

Location

Discovery Medical Research Group

Ocala, Florida, 34471, United States

Location

Innovation Medical Research Center, Inc

Palmetto Bay, Florida, 33157, United States

Location

Volunteer Medical Research

Port Charlotte, Florida, 33952, United States

Location

University of South Florida

Tampa, Florida, 33606, United States

Location

Florida Premier Research Institute, LLC

Winter Park, Florida, 32789, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Georgia Nephrology, LLC

Lawrenceville, Georgia, 30046, United States

Location

Boise Kidney & Hypertension, PLLC

Caldwell, Idaho, 83605, United States

Location

Boise Kidney & Hypertension, PLLC

Meridian, Idaho, 83642, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Chicago

Chicago, Illinois, 60617, United States

Location

Loyola University Chicago

Maywood, Illinois, 60153, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66224, United States

Location

Cotton O'Neil Clinical Research Center

Topeka, Kansas, 66606, United States

Location

Ascension Via Christi Research

Wichita, Kansas, 67214, United States

Location

Kansas Nephrology Research Institute, LLC

Wichita, Kansas, 67214, United States

Location

Renal Associates of Baton Rouge

Baton Rouge, Louisiana, 70808, United States

Location

Northwest Louisiana Nephrology

Shreveport, Louisiana, 71101, United States

Location

University of Maryland School of Medicine

Baltimore, Maryland, 21201, United States

Location

The Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

KidneyCare and Tranplant Services of New England

Springfield, Massachusetts, 01104, United States

Location

Renal and Transplant Associates of New England, PC

Springfield, Massachusetts, 01107, United States

Location

Paragon Health PC d/b/a Nephrology Center PC

Kalamazoo, Michigan, 49007, United States

Location

Michigan Kidney Consultants

Pontiac, Michigan, 48341, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Clinical Research Consultants, LLC

Kansas City, Missouri, 64111, United States

Location

Washington University in St. Louis

St Louis, Missouri, 63110, United States

Location

KSOSN

Las Vegas, Nevada, 89129, United States

Location

Nephrology Associates, P.C.

Flushing, New York, 11355, United States

Location

Division of Kidney Diseases and Hypertension

Great Neck, New York, 11021, United States

Location

NYU Winthrop Hospital

Mineola, New York, 11501, United States

Location

Mountain Kidney & Hypertension Associates

Asheville, North Carolina, 28801, United States

Location

Metrolina Nephrology Associates

Charlotte, North Carolina, 28204, United States

Location

North Carolina Nephrology, P.A. 2nd Floor

Raleigh, North Carolina, 27609, United States

Location

Brookview Hills Research Associates, LLC

Winston-Salem, North Carolina, 27103, United States

Location

Cincinnati VA Medical Center

Cincinnati, Ohio, 45220, United States

Location

University of Cincinnati College of Medicine

Cincinnati, Ohio, 45267, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Remington-Davis Clinical Research

Columbus, Ohio, 43215, United States

Location

Northeast Clinical Research Center

Bethlehem, Pennsylvania, 18017, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19014, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Columbia Nephrology Associates, PA

Columbia, South Carolina, 29203, United States

Location

Nephrology Associates, P.C.

Nashville, Tennessee, 37205, United States

Location

TTUHSC

Amarillo, Texas, 79106, United States

Location

Arlington Nephrology, PA

Arlington, Texas, 76015, United States

Location

Research Management, Inc.

Austin, Texas, 78751, United States

Location

Research Management, Inc.

Austin, Texas, 78758, United States

Location

Liberty Research Center

Dallas, Texas, 75230, United States

Location

Renal Disease Research Institute

Dallas, Texas, 75235, United States

Location

Davita Clinical Research

El Paso, Texas, 79925, United States

Location

DaVita Med Center

Houston, Texas, 77004, United States

Location

Clinical Advancement Center

San Antonio, Texas, 78215, United States

Location

University of Vermont Medical Center

Burlington, Vermont, 05401, United States

Location

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

Nephrology Associates of Northern Virginia, Inc.

Fairfax, Virginia, 22033, United States

Location

Swedish Medical Center

Seattle, Washington, 98052, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Milwaukee Nephrologists, SC

Wauwatosa, Wisconsin, 53226, United States

Location

Renal Research

Gosford, New South Wales, 2250, Australia

Location

John Hunter Hospital

New Lambton, New South Wales, 2305, Australia

Location

Westmead Hospital

Sydney, New South Wales, 2145, Australia

Location

Sunshine Coast University Hospital

Birtinya, Queensland, 4575, Australia

Location

Royal Brisbane and Women's Hospital

Herston, Queensland, 4029, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Monash Health

Clayton, Victoria, 3168, Australia

Location

Melbourne Health

Parkville, Victoria, 3050, Australia

Location

Melbourne Renal Research Group

Reservoir, Victoria, 3073, Australia

Location

Fiona Stanley Hospital

Murdoch, Western Australia, 6150, Australia

Location

Nephrology, Cliniques U St-Luc

Brussels, 1200, Belgium

Location

Universitair Ziekenhuis Brussel (VUB)

Brussels, B-1090, Belgium

Location

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

Leuven, 3000, Belgium

Location

Chu Liege

Liège, 4000, Belgium

Location

FN Brno

Brno, 62500, Czechia

Location

Nephrology Dept., General Teaching Hospital

Prague, 12808, Czechia

Location

IKEM

Prague, 14021, Czechia

Location

University Hospital La Cavale Blanche

Brest, 29200, France

Location

Chu Grenoble Alpes

Grenoble, 38043, France

Location

Hospital Henri-Mondor AP-HP

Le Kremlin-Bicêtre, 94270, France

Location

CHU de Nantes

Nantes, 44093, France

Location

Hopital Necker, Universite Paris Descartes

Paris, 75015, France

Location

Universitätsklinikum Essen

Essen, 45147, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Klinikum rechts der Isar der TU München

München, 81675, Germany

Location

Renal Division, ASST Santi Paolo e Carlo

Milan, 20153, Italy

Location

Università di Modena e Reggio Emilia

Modena, 41124, Italy

Location

ICS Maugeri SpA SB

Pavia, 27100, Italy

Location

Fondazione Policlinico Gemelli

Roma, 168, Italy

Location

Hokkaido University Hospital

Hokkaido, 060-8648, Japan

Location

Toranomon Hospital Kajigaya

Kanagawa, 213-8587, Japan

Location

Japan Community Healthcare Organization Sendai Hospital

Miyagi, 981-8501, Japan

Location

Niigata University Medical & Dental Hospital

Niigata, 951-8520, Japan

Location

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

Osaka, 534-0021, Japan

Location

Osaka City University Hospital

Osaka, 545-8586, Japan

Location

Osaka University Hospital

Osaka, 565-0871, Japan

Location

Toranomon Hospital

Tokyo, 105-8470, Japan

Location

Juntendo University Hospital

Tokyo, 113-8431, Japan

Location

Tokyo Women's Medical University Hospital

Tokyo, 162-8666, Japan

Location

Hospital Universitario de Badajoz

Badajoz, 6070, Spain

Location

Hospital Del Mar

Barcelona, 8003, Spain

Location

Fundacio Puigvert

Barcelona, 8025, Spain

Location

Hospital Universitario Reina Sofía

Córdoba, 14004, Spain

Location

Hospital Universitario Virgen de las Nieves

Granada, 18012, Spain

Location

Hospital Lucus Augusti

Lugo, 27003, Spain

Location

Fundación Jiménez Díaz

Madrid, 28040, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital de Getafe

Madrid, 28905, Spain

Location

Hospital Universitario Marques de Valdecilla

Santander, 39008, Spain

Location

Hospital Universitario Dr Peset

Valencia, 46017, Spain

Location

North Bristol NHS Trust

Bristol, BS10 5NB, United Kingdom

Location

Manchester University NHS Foundation Trust

Manchester, M13 9WL, United Kingdom

Location

Nottingham University Hospitals

Nottingham, NG5 1PB, United Kingdom

Location

Morriston Hospital

Swansea, SA66NL, United Kingdom

Location

Related Publications (1)

  • 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.

MeSH Terms

Conditions

Polycystic Kidney, Autosomal Dominant

Interventions

bardoxolone methyl

Condition Hierarchy (Ancestors)

Polycystic Kidney DiseasesKidney Diseases, CysticKidney DiseasesUrologic DiseasesFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesMale Urogenital DiseasesAbnormalities, MultipleCongenital AbnormalitiesCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesCiliopathiesGenetic Diseases, Inborn

Limitations and Caveats

Due to discontinuation of all bardoxolone chronic kidney disease programs, study was terminated early.

Results Point of Contact

Title
US Biogen Clinical Trial Center
Organization
Biogen

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 12, 2019

First Posted

April 17, 2019

Study Start

May 29, 2019

Primary Completion

August 8, 2023

Study Completion

August 8, 2023

Last Updated

June 3, 2025

Results First Posted

June 11, 2024

Record last verified: 2025-05

Data Sharing

IPD Sharing
Will share

In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/

More information

Locations