A Trial of Bardoxolone Methyl in Patients With ADPKD - FALCON

ADPKD Clinical Trial

— FALCON  

Official title:

A Phase 3 Trial of the Efficacy and Safety of Bardoxolone Methyl in Patients With Autosomal Dominant Polycystic Kidney Disease

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03918447
• Other study ID #: 402-C-1808
• Status: Terminated
• Phase: Phase 3
• Start date: May 29, 2019
• Est. completion date: August 8, 2023

Study information

• Verified date: June 2024
• Source: Biogen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 667
• Est. completion date: August 8, 2023
• Est. primary completion date: August 8, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• ADPKD
• Arthrogryposis
• Autosomal Dominant Polycystic Kidney
• Polycystic Kidney Diseases
• Polycystic Kidney, Autosomal Dominant

Intervention

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.
• Placebo oral capsule
Capsule containing an inert placebo

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Sunshine Coast University Hospital	Birtinya	Queensland
Australia	Monash Health	Clayton	Victoria
Australia	Renal Research	Gosford	New South Wales
Australia	Royal Brisbane and Women's Hospital	Herston	Queensland
Australia	Fiona Stanley Hospital	Murdoch	Western Australia
Australia	John Hunter Hospital	New Lambton	New South Wales
Australia	Melbourne Health	Parkville	Victoria
Australia	Melbourne Renal Research Group	Reservoir	Victoria
Australia	Westmead Hospital	Sydney	New South Wales
Belgium	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
Czechia	FN Brno	Brno
Czechia	Nephrology Dept., General Teaching Hospital	Prague
Czechia	IKEM	Praha
France	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
Germany	Universitätsklinikum Essen	Essen
Germany	Medizinische Hochschule Hannover	Hanover
Germany	Klinikum rechts der Isar der TU München	München
Italy	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
Japan	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	Juntendo University Hospital	Tokyo
Japan	Tokyo Women's Medical University Hospital	Tokyo
Japan	Toranomon Hospital	Tokyo
Spain	Hospital Universitario de Badajoz	Badajoz
Spain	Fundacio Puigvert	Barcelona
Spain	Hospital Del Mar	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 de Getafe	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Marques de Valdecilla	Santander
Spain	Hospital Universitario Dr Peset	Valencia
United Kingdom	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 States	TTUHSC	Amarillo	Texas
United States	Arlington Nephrology, PA	Arlington	Texas
United States	Western Nephrology	Arvada	Colorado
United States	Mountain Kidney & Hypertension Associates	Asheville	North Carolina
United States	Emory University	Atlanta	Georgia
United States	University of Colorado Anschutz Medical Center	Aurora	Colorado
United States	Research Management, Inc.	Austin	Texas
United States	Research Management, Inc.	Austin	Texas
United States	The Johns Hopkins University	Baltimore	Maryland
United States	University of Maryland School of Medicine	Baltimore	Maryland
United States	Renal Associates of Baton Rouge	Baton Rouge	Louisiana
United States	Northeast Clinical Research Center	Bethlehem	Pennsylvania
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	University of Vermont Medical Center	Burlington	Vermont
United States	Boise Kidney & Hypertension, PLLC	Caldwell	Idaho
United States	Metrolina Nephrology Associates	Charlotte	North Carolina
United States	University of Virginia	Charlottesville	Virginia
United States	Northwestern University	Chicago	Illinois
United States	University of Chicago	Chicago	Illinois
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	Columbia Nephrology Associates, PA	Columbia	South Carolina
United States	Remington-Davis Clinical Research	Columbus	Ohio
United States	Liberty Research Center	Dallas	Texas
United States	Renal Disease Research Institute	Dallas	Texas
United States	Denver Nephrologist, PC	Denver	Colorado
United States	Kidney Associates of Colorado	Denver	Colorado
United States	Rancho Research Institute	Downey	California
United States	Davita Clinical Research	El Paso	Texas
United States	Nephrology Associates of Northern Virginia, Inc.	Fairfax	Virginia
United States	Nephrology Associates, P.C.	Flushing	New York
United States	AKDHC	Glendale	Arizona
United States	Division of Kidney Diseases and Hypertension	Great Neck	New York
United States	Nephrology Associates PC	Homewood	Alabama
United States	DaVita Med Center	Houston	Texas
United States	Nephrology Consultants, LLC	Huntsville	Alabama
United States	Paragon Health PC d/b/a Nephrology Center PC	Kalamazoo	Michigan
United States	Clinical Research Consultants, LLC	Kansas City	Missouri
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	California Institute Renal Research	La Mesa	California
United States	KSOSN	Las Vegas	Nevada
United States	Georgia Nephrology, LLC	Lawrenceville	Georgia
United States	Keck USC/LAC	Los Angeles	California
United States	University of California, Los Angeles	Los Angeles	California
United States	Loyola University Chicago	Maywood	Illinois
United States	Boise Kidney & Hypertension, PLLC	Meridian	Idaho
United States	Aventiv Research, Inc	Mesa	Arizona
United States	University of Miami	Miami	Florida
United States	Pro-Care Research Center, Corp.	Miami Gardens	Florida
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	NYU Winthrop Hospital	Mineola	New York
United States	Nephrology Associates, P.C.	Nashville	Tennessee
United States	Yale University School of Medicine	New Haven	Connecticut
United States	Amicis Research Center	Northridge	California
United States	Discovery Medical Research Group	Ocala	Florida
United States	Innovation Medical Research Center, Inc	Palmetto Bay	Florida
United States	Stanford University	Palo Alto	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Michigan Kidney Consultants	Pontiac	Michigan
United States	Volunteer Medical Research	Port Charlotte	Florida
United States	North Carolina Nephrology, P.A. 2nd Floor	Raleigh	North Carolina
United States	Apex Research of Riverside	Riverside	California
United States	Mayo Clinic	Rochester	Minnesota
United States	Washington University in St. Louis	Saint Louis	Missouri
United States	Clinical Advancement Center	San Antonio	Texas
United States	University of California San Francisco	San Francisco	California
United States	Swedish Medical Center	Seattle	Washington
United States	Northwest Louisiana Nephrology	Shreveport	Louisiana
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	University of South Florida	Tampa	Florida
United States	Cotton O'Neil Clinical Research Center	Topeka	Kansas
United States	University of Arizona	Tucson	Arizona
United States	Milwaukee Nephrologists, SC	Wauwatosa	Wisconsin
United States	Western Nephrology and Mineral Bone Disease, PC	Westminster	Colorado
United States	Ascension Via Christi Research	Wichita	Kansas
United States	Kansas Nephrology Research Institute, LLC	Wichita	Kansas
United States	Brookview Hills Research Associates, LLC	Winston-Salem	North Carolina
United States	Florida Premier Research Institute, LLC	Winter Park	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Reata, a wholly owned subsidiary of Biogen

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Treatment Period: Change From Baseline in eGFR at 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.	Baseline, Week 100