Clinical trial NCT03918447: A Trial of Bardoxolone Methyl in Patients With ADPKD - FALCON
Official title: A Phase 3 Trial of the Efficacy and Safety of Bardoxolone Methyl in Patients With Autosomal Dominant Polycystic Kidney Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Autosomal Dominant Polycystic Kidney
ADPKD
Keywords: Bardoxolone Methyl
RTA 402
Autosomal Dominant Polycystic Kidney Disease
ADPKD
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2019-04-17
Enrollment: 667
Sex: ALL
Minimum age (years): 12
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Off-treatment Period: Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 108
timeFrame: Baseline, Week 108
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
timeFrame: From first dose of the study drug up to end of follow-up (up to Week 112)
Secondary outcomes:
measure: Treatment Period: Change From Baseline in eGFR at Week 100
timeFrame: Baseline, Week 100
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Homewood
country: United States
facility: Nephrology Associates PC
state: Alabama
city: Huntsville
country: United States
facility: Nephrology Consultants, LLC
state: Alabama
city: Glendale
country: United States
facility: AKDHC
state: Arizona
city: Mesa
country: United States
facility: Aventiv Research, Inc
state: Arizona
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: Downey
country: United States
facility: Rancho Research Institute
state: California
city: La Mesa
country: United States
facility: California Institute Renal Research
state: California
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
city: Los Angeles
country: United States
facility: Keck USC/LAC
state: California
city: Northridge
country: United States
facility: Amicis Research Center
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Riverside
country: United States
facility: Apex Research of Riverside
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Arvada
country: United States
facility: Western Nephrology
state: Colorado
city: Aurora
country: United States
facility: University of Colorado Anschutz Medical Center
state: Colorado
city: Denver
country: United States
facility: Kidney Associates of Colorado
state: Colorado
city: Denver
country: United States
facility: Denver Nephrologist, PC
state: Colorado
city: Westminster
country: United States
facility: Western Nephrology and Mineral Bone Disease, PC
state: Colorado
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Miami Gardens
country: United States
facility: Pro-Care Research Center, Corp.
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Ocala
country: United States
facility: Discovery Medical Research Group
state: Florida
city: Palmetto Bay
country: United States
facility: Innovation Medical Research Center, Inc
state: Florida
city: Port Charlotte
country: United States
facility: Volunteer Medical Research
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Winter Park
country: United States
facility: Florida Premier Research Institute, LLC
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Lawrenceville
country: United States
facility: Georgia Nephrology, LLC
state: Georgia
city: Caldwell
country: United States
facility: Boise Kidney & Hypertension, PLLC
state: Idaho
city: Meridian
country: United States
facility: Boise Kidney & Hypertension, PLLC
state: Idaho
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Maywood
country: United States
facility: Loyola University Chicago
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Topeka
country: United States
facility: Cotton O'Neil Clinical Research Center
state: Kansas
city: Wichita
country: United States
facility: Ascension Via Christi Research
state: Kansas
city: Wichita
country: United States
facility: Kansas Nephrology Research Institute, LLC
state: Kansas
city: Baton Rouge
country: United States
facility: Renal Associates of Baton Rouge
state: Louisiana
city: Shreveport
country: United States
facility: Northwest Louisiana Nephrology
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland School of Medicine
state: Maryland
city: Baltimore
country: United States
facility: The Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Springfield
country: United States
facility: KidneyCare and Tranplant Services of New England
state: Massachusetts
city: Springfield
country: United States
facility: Renal and Transplant Associates of New England, PC
state: Massachusetts
city: Kalamazoo
country: United States
facility: Paragon Health PC d/b/a Nephrology Center PC
state: Michigan
city: Pontiac
country: United States
facility: Michigan Kidney Consultants
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Kansas City
country: United States
facility: Clinical Research Consultants, LLC
state: Missouri
city: Saint Louis
country: United States
facility: Washington University in St. Louis
state: Missouri
city: Las Vegas
country: United States
facility: KSOSN
state: Nevada
city: Flushing
country: United States
facility: Nephrology Associates, P.C.
state: New York
city: Great Neck
country: United States
facility: Division of Kidney Diseases and Hypertension
state: New York
city: Mineola
country: United States
facility: NYU Winthrop Hospital
state: New York
city: Asheville
country: United States
facility: Mountain Kidney & Hypertension Associates
state: North Carolina
city: Charlotte
country: United States
facility: Metrolina Nephrology Associates
state: North Carolina
city: Raleigh
country: United States
facility: North Carolina Nephrology, P.A. 2nd Floor
state: North Carolina
city: Winston-Salem
country: United States
facility: Brookview Hills Research Associates, LLC
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati VA Medical Center
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati College of Medicine
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: Remington-Davis Clinical Research
state: Ohio
city: Bethlehem
country: United States
facility: Northeast Clinical Research Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Columbia
country: United States
facility: Columbia Nephrology Associates, PA
state: South Carolina
city: Nashville
country: United States
facility: Nephrology Associates, P.C.
state: Tennessee
city: Amarillo
country: United States
facility: TTUHSC
state: Texas
city: Arlington
country: United States
facility: Arlington Nephrology, PA
state: Texas
city: Austin
country: United States
facility: Research Management, Inc.
state: Texas
city: Austin
country: United States
facility: Research Management, Inc.
state: Texas
city: Dallas
country: United States
facility: Liberty Research Center
state: Texas
city: Dallas
country: United States
facility: Renal Disease Research Institute
state: Texas
city: El Paso
country: United States
facility: Davita Clinical Research
state: Texas
city: Houston
country: United States
facility: DaVita Med Center
state: Texas
city: San Antonio
country: United States
facility: Clinical Advancement Center
state: Texas
city: Burlington
country: United States
facility: University of Vermont Medical Center
state: Vermont
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Fairfax
country: United States
facility: Nephrology Associates of Northern Virginia, Inc.
state: Virginia
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Wauwatosa
country: United States
facility: Milwaukee Nephrologists, SC
state: Wisconsin
city: Gosford
country: Australia
facility: Renal Research
state: New South Wales
city: New Lambton
country: Australia
facility: John Hunter Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Birtinya
country: Australia
facility: Sunshine Coast University Hospital
state: Queensland
city: Herston
country: Australia
facility: Royal Brisbane and Women's Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Clayton
country: Australia
facility: Monash Health
state: Victoria
city: Parkville
country: Australia
facility: Melbourne Health
state: Victoria
city: Reservoir
country: Australia
facility: Melbourne Renal Research Group
state: Victoria
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital
state: Western Australia
city: Brussels
country: Belgium
facility: Nephrology, Cliniques U St-Luc
city: Brussels
country: Belgium
facility: Universitair Ziekenhuis Brussel (VUB)
city: Leuven
country: Belgium
facility: University Hospitals Leuven, Dept. of Nephrology, Dialysis and Renal Transplantation
city: Liège
country: Belgium
facility: Chu Liege
city: Brno
country: Czechia
facility: FN Brno
city: Prague
country: Czechia
facility: Nephrology Dept., General Teaching Hospital
city: Praha
country: Czechia
facility: IKEM
city: Brest
country: France
facility: University Hospital La Cavale Blanche
city: Grenoble
country: France
facility: Chu Grenoble Alpes
city: Le Kremlin-Bicêtre
country: France
facility: Hospital Henri-Mondor AP-HP
city: Nantes
country: France
facility: CHU de Nantes
city: Paris
country: France
facility: Hopital Necker, Universite Paris Descartes
city: Essen
country: Germany
facility: Universitätsklinikum Essen
city: Hanover
country: Germany
facility: Medizinische Hochschule Hannover
city: München
country: Germany
facility: Klinikum rechts der Isar der TU München
city: Milan
country: Italy
facility: Renal Division, ASST Santi Paolo e Carlo
city: Modena
country: Italy
facility: Università di Modena e Reggio Emilia
city: Pavia
country: Italy
facility: ICS Maugeri SpA SB
city: Roma
country: Italy
facility: Fondazione Policlinico Gemelli
city: Hokkaido
country: Japan
facility: Hokkaido University Hospital
city: Kanagawa
country: Japan
facility: Toranomon Hospital Kajigaya
city: Miyagi
country: Japan
facility: Japan Community Healthcare Organization Sendai Hospital
city: Niigata
country: Japan
facility: Niigata University Medical & Dental Hospital
city: Osaka
country: Japan
facility: Local Incorporated Administrative Agency Osaka City Hospital Organization Osaka City General Hospital
city: Osaka
country: Japan
facility: Osaka City University Hospital
city: Osaka
country: Japan
facility: Osaka University Hospital
city: Tokyo
country: Japan
facility: Toranomon Hospital
city: Tokyo
country: Japan
facility: Juntendo University Hospital
city: Tokyo
country: Japan
facility: Tokyo Women's Medical University Hospital
city: Badajoz
country: Spain
facility: Hospital Universitario de Badajoz
city: Barcelona
country: Spain
facility: Hospital Del Mar
city: Barcelona
country: Spain
facility: Fundacio Puigvert
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofía
city: Granada
country: Spain
facility: Hospital Universitario Virgen de las Nieves
city: Lugo
country: Spain
facility: Hospital Lucus Augusti
city: Madrid
country: Spain
facility: Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Madrid
country: Spain
facility: Hospital de Getafe
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla
city: Valencia
country: Spain
facility: Hospital Universitario Dr Peset
city: Bristol
country: United Kingdom
facility: North Bristol NHS Trust
city: Manchester
country: United Kingdom
facility: Manchester University NHS Foundation Trust
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals
city: Swansea
country: United Kingdom
facility: Morriston Hospital
Study officials:
References: