Clinical trial NCT02278341: Roxadustat in the Treatment of Anemia in End Stage Renal Disease (ESRD) Patients on Stable Dialysis
Official title: A Phase 3, Randomized, Open-Label, Active-Controlled Study to Evaluate the Efficacy and Safety of Roxadustat in the Maintenance Treatment of Anemia in End Stage Renal Disease Patients on Stable Dialysis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Anemia
End Stage Renal Disease (ESRD)
Keywords: ASP1517
FG-4592
Anemia
End Stage Renal Disease (ESRD)
Erythropoetin Stimulating Agents (ESAs)
Chronic Kidney Disease
Hematopoetic Agents
HIF-PH inhibitor
Hemoglobin
Dialysis
roxadustat
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
Collaborators: name: FibroGen
First posted: 2014-10-30
Enrollment: 838
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study was conducted to explore a new therapy for anemia in participants with end stage renal disease (ESRD) on dialysis. Anemia is a reduced number of red blood cells or hemoglobin. Hemoglobin (which contains iron) is important for the transport of oxygen in your blood. The purpose of this study was to evaluate if roxadustat is effective and safe in the maintenance treatment of anemia in ESRD participants on stable dialysis. Roxadustat was compared to epoetin alfa and darbepoetin alfa, commercially available medicines for treatment of anemia.

Detailed description: This study consisted of three study periods as follows:

* Screening Period: up to 6 weeks
* Treatment Period: a minimum of 52 weeks up to a maximum of 104 weeks
* Follow-up Period: 4 weeks

Eligibility criteria: Inclusion Criteria:

Main Inclusion:

* Participant is on stable hemodialysis (HD), hemodiafiltration (HDF) or peritoneal dialysis (PD) treatment with the same mode of dialysis for ≥4 months prior to randomization.
* Participant is on IV or SC epoetin or IV or SC darbepoetin alfa treatment for ≥8 weeks prior to randomization with stable weekly doses (during 4 weeks prior to randomization).
* Mean of the participant's three most recent Hb values, as measured by central laboratory, during the Screening Period.
* Participant's alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are ≤3 x upper limit of normal (ULN), and total bilirubin (TBL) is ≤1.5 x ULN

Exclusion Criteria:

Main Exclusion:

* Participant has received a red blood cell (RBC) transfusion within 8 weeks prior to randomization.
* Participant has a known hereditary hematologic disease such as thalassemia or sickle cell anemia, pure red cell aplasia, or other known causes for anemia other than Chronic Kidney Disease (CKD).
* Participant has had a myocardial infarction, acute coronary syndrome, stroke, seizure, or a thrombotic/thrombo-embolic event (e.g., deep vein thrombosis or pulmonary embolism) within 12 weeks prior to randomization.
* Participant has had uncontrolled hypertension, in the opinion of the investigator, within 2 weeks prior to randomization.
* Participant has a history of malignancy, except for the following: cancers determined to be cured or in remission for ≥5 years, curatively resected basal cell or squamous cell skin cancers, cervical cancer in situ, or resected colonic polyps.
* Participant has had any prior organ transplant (that has not been explanted), or participant is scheduled for organ transplantation.

Primary outcomes:
measure: Change From Baseline (BL) to the Average Hemoglobin (Hb) in Weeks 28-36 Without Rescue Therapy [EU (EMA)]
timeFrame: Baseline and weeks 28 to 36
measure: Change From BL to the Average Hb in Weeks 28 to 52 Regardless of Rescue Therapy [US (FDA)]
timeFrame: Baseline and weeks 28 to 52
Secondary outcomes:
measure: Percentage of Participants With Hb Response During Weeks 28 to 36
timeFrame: Weeks 28 to 36
measure: Change From BL in Low Density Lipoprotein Cholesterol (LDL-C) to the Average LDL-C of Weeks 12 to 28
timeFrame: Baseline and weeks 12 to 28
measure: Mean Monthly Intravenous (IV) Iron Use
timeFrame: Day 1 to week 36
measure: Change From BL in Short Form-36 (SF-36) Health Survey Physical Functioning (PF) Sub-score to the Average of Weeks 12 to 28
timeFrame: Baseline and weeks 12 to 28
measure: Change From BL in SF-36 Vitality (VT) Sub-score to the Average of Weeks 12 to 28
timeFrame: Baseline and weeks 12 to 28
measure: Change From BL in Mean Arterial Pressure (MAP) to the Average of Weeks 20 to 28
timeFrame: Baseline and weeks 20 to 28
measure: Time to First Occurrence of an Increase in Blood Pressure
timeFrame: Weeks 1 to 36
measure: Change From BL in Mean Arterial Pressure (MAP) to the Average MAP Value of Weeks 20 to 28
timeFrame: Baseline and weeks 20 to 28
measure: Time to First Occurrence of an Increase in Blood Pressure
timeFrame: Weeks 1 to 36
measure: Percentage of Participants With a Hb Response During Weeks 28 and 36 Regardless of Use of Rescue Therapy
timeFrame: Weeks 28 to 36
measure: Change From BL in Hb to Each Postdosing Time Point
timeFrame: Baseline and weeks 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14, 16, 18,20, 22, 24, 26, 28, 30, 32, 34, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72,76, 80, 84, 88, 92, 96, 100, and 104
measure: Hb Level Averaged Over Weeks 28 to 36, 44 to 52, and 96 to 104 Without Use of Rescue Therapy
timeFrame: Weeks 28 to 36, 44 to 52, and 96 to 104
measure: Change From BL in Hb to the Average of Weeks 28 to 36, 44 to 52, and 96 to 104 Regardless of the Use of Rescue Therapy
timeFrame: Baseline and weeks 28 to 36, 44 to 52, and 96 to 104
measure: Percentage of Hb Values ≥ 10 g/dL in Weeks 28 to 36, 44 to 52, and 96 to 104 Without Use of Rescue Therapy
timeFrame: Weeks 28-36, 44-52 and 96-104
measure: Percentage of Hb Values Within 10.0 to 12.0 g/dL in Weeks 28 to 36, 44 to 52, and 96 to 104 Without Use of Rescue Therapy
timeFrame: Weeks 28-36, 44-52 and 96-104
measure: Number of Hospitalizations
timeFrame: Baseline to End of Treatment (EOT) (Up to week 104)
measure: Number of Days of Hospitalization Per Year
timeFrame: Baseline to EOT (Up to week 104)
measure: Time to First Hospitalization
timeFrame: Baseline to EOT (Up to week 104)
measure: Time to First Use of Rescue Therapy
timeFrame: Baseline to EOT (Up to week 104)
measure: Time to First RBC Transfusion
timeFrame: Baseline to EOT (Up to week 104)
measure: Mean Monthly Number of RBC Packs Per Participant
timeFrame: Baseline to EOT (Up to week 104)
measure: Mean Monthly Volume of RBC Transfusion Per Participant
timeFrame: Baseline to EOT (Up to week 104)
measure: Time to First Use of IV Iron Supplementation
timeFrame: Baseline to EOT (Up to week 104)
measure: Mean Monthly Intravenous (IV) Iron Per Participant During Weeks 37-52 and Weeks 53-104
timeFrame: Weeks 37-52 and weeks 53-104
measure: Percentage of Participants With Oral Iron Use Only
timeFrame: Baseline to EOT (Up to week 104)
measure: Change From BL to Each Post-dosing Study Visit in Total Cholesterol
timeFrame: Baseline and weeks 8, 28, 52, 104
measure: Change From BL to Each Post-dosing Study Visit in LDL-C/High-density Lipoprotein Cholesterol (HDL-C) Ratio
timeFrame: Baseline and weeks 8, 28, 52, 104
measure: Change From BL to Each Postdosing Study Visit in Non-HDL Cholesterol
timeFrame: Baseline and weeks 8, 28, 52, 104
measure: Change From BL to Each Postdosing Study Visit in Apolipoproteins A1 (ApoA1)
timeFrame: Baseline and weeks 8, 28, 52, 104
measure: Change From BL to Each Postdosing Study Visit in Apolipoproteins B (ApoB)
timeFrame: Baseline and weeks 8, 28, 52, 104
measure: Change From BL to Each Postdosing Study Visit in ApoB/ApoA1 Ratio
timeFrame: Baseline and weeks 8, 28, 52, 104
measure: Number of Participants With Mean LDL Cholesterol < 100 mg/dL Over Weeks 12 to 28
timeFrame: Weeks 12 to 28
measure: Number of Participants With CKD Who Achieved Antihypertensive Treatment Goal
timeFrame: Weeks 12 to 28
measure: Change From BL to the Average of Weeks 12 to 28 in SF-36 Physical Component Score (PCS)
timeFrame: Baseline and weeks 12 to 28
measure: Change From BL to the Average of Weeks 12 to 28 in Anemia Subscale (AnS) ("Additional Concerns") of Functional Assessment of Cancer Therapy-Anemia (FACT-An) Score
timeFrame: Baseline and weeks 12 to 28
measure: Change From BL to the Average Value of Weeks 12 to 28 in Total FACT-An Score
timeFrame: Baseline and weeks 12 to 28
measure: Change From BL to the Average of Weeks 12 to 28 in Euroqol Questionnaire-5 Dimensions 5 Levels (EQ-5D 5L) Visual Analogue Scale (VAS) Score
timeFrame: Baseline and weeks 12 to 28
measure: Percentage of Participants With Improvements Measured by Patients' Global Impression of Change (PGIC)
timeFrame: Baseline and weeks 8, 12, 28, 36, 52, 76, 104
measure: Change From BL in Serum Hepcidin
timeFrame: Baseline and weeks 4, 12, 20, 36, 52, 104, and End of Study (EOS - up to 108 weeks)
measure: Change From BL in Serum Ferritin
timeFrame: Baseline and weeks 4, 8, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 104, and EOS (up to 108 weeks)
measure: Change From BL in Transferrin Saturation (TSAT)
timeFrame: Baseline and weeks 4, 8, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 104 and EOS (up to 108 weeks)
measure: Change From BL in Glycated Hemoglobin (HbA1c) Level to Weeks 12, 28, 36, 44, 52, 60, 84, 104 and EOS (up to Week 108)
timeFrame: Baseline and weeks 12, 28, 36, 44, 52, 60, 84, 104 and EOS (up to 108 weeks)
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Baseline up to EOS (Up to week 108)
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Site BE32004
state: Flemish Brabant
city: Aalst
country: Belgium
facility: Site BE32001
city: Antwerpen
country: Belgium
facility: Site BE32019
city: Antwerp
country: Belgium
facility: Site BE32002
city: Baudour
country: Belgium
facility: Site BE32012
city: Bonheiden
country: Belgium
facility: Site BE32017
city: Leuven
country: Belgium
facility: Site BE32003
city: Liege
country: Belgium
facility: Site BE32013
city: Roeselare
country: Belgium
facility: Site BE32011
city: Blagoevgrad
country: Bulgaria
facility: Site BG35925
city: Haskovo
country: Bulgaria
facility: Site BG35931
city: Pleven
country: Bulgaria
facility: Site BG35915
city: Plovdiv
country: Bulgaria
facility: Site BG35909
city: Plovdiv
country: Bulgaria
facility: Site BG35919
city: Rousse
country: Bulgaria
facility: Site BG35920
city: Shumen
country: Bulgaria
facility: Site BG35938
city: Sofia
country: Bulgaria
facility: Site BG35924
city: Sofia
country: Bulgaria
facility: Site BG35906
city: Sofia
country: Bulgaria
facility: Site BG35921
city: Stara Zagora
country: Bulgaria
facility: Site BG35907
city: Varna
country: Bulgaria
facility: Site BG35916
city: Varna
country: Bulgaria
facility: Site BG35918
city: Veliko Tarnovo
country: Bulgaria
facility: Site BG35903
city: Yambol
country: Bulgaria
facility: Site BG35937
city: Zagreb
country: Croatia
facility: Site HR38509
state: Grad Zagreb
city: Cakovec
country: Croatia
facility: Site HR38508
city: Karlovac
country: Croatia
facility: Site HR38505
city: Osijek
country: Croatia
facility: Site HR38507
city: Rijeka
country: Croatia
facility: Site HR38506
city: Slavonski Brod
country: Croatia
facility: Site HR38504
city: Zadar
country: Croatia
facility: Site HR38501
city: Liberec
country: Czechia
facility: Site CZ42008
city: Praha 6
country: Czechia
facility: Site CZ42021
city: Rakovnik
country: Czechia
facility: Site CZ42015
city: Amiens cedex 1
country: France
facility: Site FR33005
city: La Tronche
country: France
facility: Site FR33010
city: Saint Ouen
country: France
facility: Site FR33055
city: Saint Priez En Jarez
country: France
facility: Site FR33007
city: Valenciennes
country: France
facility: Site FR33056
city: Tbilisi
country: Georgia
facility: Site GE99503
city: Tbilisi
country: Georgia
facility: Site GE99504
city: Tbilisi
country: Georgia
facility: Site GE99508
city: Dormagen
country: Germany
facility: Site DE49056
state: Nordrhein-Westfalen
city: Berlin
country: Germany
facility: Site DE49067
city: Cloppenburg
country: Germany
facility: Site DE49073
city: Dresden
country: Germany
facility: Site DE49008
city: Dusseldorf
country: Germany
facility: Site DE49054
city: Frankfurt am Main
country: Germany
facility: Site DE49020
city: Hamburg
country: Germany
facility: Site DE49065
city: Heilbronn
country: Germany
facility: Site DE49075
city: Kaiserslautern
country: Germany
facility: Site DE49001
city: Muenchen
country: Germany
facility: Site DE49070
city: Solingen
country: Germany
facility: Site DE49002
city: Villingen-Schwenningen
country: Germany
facility: Site DE49071
city: Baja
country: Hungary
facility: Site HU36033
city: Esztergom
country: Hungary
facility: Site HU36036
city: Gyor
country: Hungary
facility: Site HU36031
city: Kaposvar
country: Hungary
facility: Site HU36026
city: Kistarcsa
country: Hungary
facility: Site HU36027
city: Pecs
country: Hungary
facility: Site HU36032
city: Pecs
country: Hungary
facility: Site HU36035
city: Salgotarjan
country: Hungary
facility: Site HU36034
city: Szeged
country: Hungary
facility: Site HU36004
city: Szekesfehervar
country: Hungary
facility: Site HU36046
city: Szombathely
country: Hungary
facility: Site HU36006
city: Zalsaegerszeg
country: Hungary
facility: Site HU36003
city: Prato
country: Italy
facility: Site IT39028
state: Frazione Di Galciana
city: Cremona
country: Italy
facility: Site IT39039
state: Lombardia
city: Mestre
country: Italy
facility: Site IT39014
state: Venezia
city: Brescia
country: Italy
facility: Site IT39010
city: Lecco
country: Italy
facility: Site IT39008
city: Milano
country: Italy
facility: Site IT39006
city: Modena
country: Italy
facility: Site IT39037
city: Padova
country: Italy
facility: Site IT39022
city: Pavia
country: Italy
facility: Site IT39036
city: Roma
country: Italy
facility: Site IT39005
city: Torino
country: Italy
facility: Site IT39035
city: Trieste
country: Italy
facility: Site IT39032
city: Katowice
country: Poland
facility: Site PL48002
city: Krakow
country: Poland
facility: Site PL48001
city: Szczecin
country: Poland
facility: Site PL48013
city: Warszawa
country: Poland
facility: Site PL48005
city: Wroclaw
country: Poland
facility: Site PL48006
city: Wroclaw
country: Poland
facility: Site PL48009
city: Zamosc
country: Poland
facility: Site PL48014
city: Almada
country: Portugal
facility: Site PT35121
city: Aveiro
country: Portugal
facility: Site PT35127
city: Cascais
country: Portugal
facility: Site PT35139
city: Faro
country: Portugal
facility: Site PT35117
city: Gaeiras
country: Portugal
facility: Site PT35128
city: Leiria
country: Portugal
facility: Site PT35114
city: Porto
country: Portugal
facility: Site PT35102
city: Setubal
country: Portugal
facility: Site PT35122
city: Bucharest
country: Romania
facility: Site RO40018
city: Bucharest
country: Romania
facility: Site RO40015
city: Bucharest
country: Romania
facility: Site RO40019
city: Bucuresti
country: Romania
facility: Site RO40003
city: Oradea
country: Romania
facility: Site RO40004
city: Kaluga
country: Russian Federation
facility: Site RU70008
city: Moscow
country: Russian Federation
facility: Site RU70051
city: Moscow
country: Russian Federation
facility: Site RU70005
city: Nizhny Novgorod
country: Russian Federation
facility: Site RU70003
city: Omsk
country: Russian Federation
facility: Site RU70004
city: Rostov-on-Don
country: Russian Federation
facility: Site RU70014
city: Saint Petersburg
country: Russian Federation
facility: Site RU70072
city: Saint Petersburg
country: Russian Federation
facility: Site RU70002
city: Saint-Petersburg
country: Russian Federation
facility: Site RU70011
city: Saint-Petersburg
country: Russian Federation
facility: Site RU70050
city: Sankt-Peterburg
country: Russian Federation
facility: Site RU70030
city: Smolensk
country: Russian Federation
facility: Site RU70006
city: Volgograd
country: Russian Federation
facility: Site RU70037
city: Yaroslavl
country: Russian Federation
facility: Site RU70001
city: Belgrade
country: Serbia
facility: Site RS38102
city: Belgrade
country: Serbia
facility: Site RS38105
city: Belgrade
country: Serbia
facility: Site RS38120
city: Belgrade
country: Serbia
facility: Site RS38104
city: Krusevac
country: Serbia
facility: Site RS38117
city: Nis
country: Serbia
facility: Site RS38101
city: Zrenjanin
country: Serbia
facility: Site RS38116
city: Koshice
country: Slovakia
facility: Site SK42102
city: Levice
country: Slovakia
facility: Site SK42119
city: Lučenec
country: Slovakia
facility: Site SK42120
city: Puchov
country: Slovakia
facility: Site SK42113
city: Senica
country: Slovakia
facility: Site SK42116
city: Santiago de Compostela
country: Spain
facility: Site ES34041
state: A Coruna
city: El Ejido
country: Spain
facility: Site ES34009
state: Almeria
city: Alcorcon
country: Spain
facility: Site ES34010
state: Madrid
city: Majadahonda
country: Spain
facility: Site ES34030
state: Madrid
city: Galdakao
country: Spain
facility: Site ES34011
state: Vizcaya
city: Badalona-Barcelona
country: Spain
facility: Site ES34002
city: Barcelona
country: Spain
facility: Site ES34008
city: Barcelona
country: Spain
facility: Site ES34006
city: Jaen
country: Spain
facility: Site ES34017
city: Madrid
country: Spain
facility: Site ES34037
city: Valencia
country: Spain
facility: Site ES34052
city: Brighton
country: United Kingdom
facility: Site GB44087
state: EastSussex
city: Canterbury
country: United Kingdom
facility: Site GB44011
state: Kent
city: Stoke on Trent
country: United Kingdom
facility: Site GB44080
state: Staffordshire
city: Cambridge
country: United Kingdom
facility: Site GB44008
city: Hull
country: United Kingdom
facility: Site GB44010
city: Leicester
country: United Kingdom
facility: Site GB44081
city: Liverpool
country: United Kingdom
facility: Site GB44079
city: Swansea
country: United Kingdom
facility: Site GB44001
Study officials:
affiliation: Astellas Pharma Europe B.V.
name: Study Physician
role: STUDY_DIRECTOR
References:
citation: Natale P, Palmer SC, Jaure A, Hodson EM, Ruospo M, Cooper TE, Hahn D, Saglimbene VM, Craig JC, Strippoli GF. Hypoxia-inducible factor stabilisers for the anaemia of chronic kidney disease. Cochrane Database Syst Rev. 2022 Aug 25;8(8):CD013751. doi: 10.1002/14651858.CD013751.pub2.