Roxadustat in the Treatment of Anemia in End Stage Renal Disease (ESRD) Patients on Stable Dialysis

NCT ID: NCT02278341

Last Updated: 2024-11-27

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

838 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-11-21

Study Completion Date

2018-07-06

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Anemia End Stage Renal Disease (ESRD)

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Roxadustat

Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met.

Group Type EXPERIMENTAL

Roxadustat

Intervention Type DRUG

Participants received initial dose of roxadustat orally as a tablet in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met.

Iron

Intervention Type DRUG

Oral iron treatment was recommended for supplementation to support erythropoiesis and as first-line treatment for iron deficiency, unless participant was intolerant to this treatment. For participants receiving roxadustat the recommended daily dose was 200 mg of elemental iron. Participants were advised to take roxadustat at least 1 hour before or 1 hour after oral iron. Intravenous iron supplementation for participants receiving roxadustat was allowed if all of the following criteria were met: The participant's Hb level had not responded adequately to roxadustat following two consecutive dose increases or reached the maximum dose limit, and participant's ferritin was \< 100 ng/mL (\< 220 pmol/L) or TSAT \< 20%, or the participant was intolerant of oral iron therapy. For participants treated with epoetin alfa or darbepoetin alfa, IV iron supplementation was given according to standard of care.

ESA (Erythropoiesis Stimulating Agent) treatment

Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from the epoetin alfa to darbepoetin alfa or vice versa.

Group Type ACTIVE_COMPARATOR

Epoetin alfa

Intervention Type DRUG

Participants received epoetin alfa via intravenous or subcutaneous injection, once a week, twice a week, or three times a week (TIW). Epoetin alfa dosage was adjusted to maintain Hb level within the target range. Dosing of epoetin alfa was per UK SmPC of Eprex®. Participants received IV iron supplementation according to the standard of care.

Darbepoetin alfa

Intervention Type DRUG

Participants received darbepoetin alfa via intravenous or subcutaneous injection, once a week or once every other week. Darbepoetin alfa dosage was adjusted to maintain Hb level within the target range. Dosing of darbepoetin alfa was per EU SmPC of Aranesp®. Participants received IV iron supplementation according to the standard of care.

Iron

Intervention Type DRUG

Oral iron treatment was recommended for supplementation to support erythropoiesis and as first-line treatment for iron deficiency, unless participant was intolerant to this treatment. For participants receiving roxadustat the recommended daily dose was 200 mg of elemental iron. Participants were advised to take roxadustat at least 1 hour before or 1 hour after oral iron. Intravenous iron supplementation for participants receiving roxadustat was allowed if all of the following criteria were met: The participant's Hb level had not responded adequately to roxadustat following two consecutive dose increases or reached the maximum dose limit, and participant's ferritin was \< 100 ng/mL (\< 220 pmol/L) or TSAT \< 20%, or the participant was intolerant of oral iron therapy. For participants treated with epoetin alfa or darbepoetin alfa, IV iron supplementation was given according to standard of care.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Roxadustat

Participants received initial dose of roxadustat orally as a tablet in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met.

Intervention Type DRUG

Epoetin alfa

Participants received epoetin alfa via intravenous or subcutaneous injection, once a week, twice a week, or three times a week (TIW). Epoetin alfa dosage was adjusted to maintain Hb level within the target range. Dosing of epoetin alfa was per UK SmPC of Eprex®. Participants received IV iron supplementation according to the standard of care.

Intervention Type DRUG

Darbepoetin alfa

Participants received darbepoetin alfa via intravenous or subcutaneous injection, once a week or once every other week. Darbepoetin alfa dosage was adjusted to maintain Hb level within the target range. Dosing of darbepoetin alfa was per EU SmPC of Aranesp®. Participants received IV iron supplementation according to the standard of care.

Intervention Type DRUG

Iron

Oral iron treatment was recommended for supplementation to support erythropoiesis and as first-line treatment for iron deficiency, unless participant was intolerant to this treatment. For participants receiving roxadustat the recommended daily dose was 200 mg of elemental iron. Participants were advised to take roxadustat at least 1 hour before or 1 hour after oral iron. Intravenous iron supplementation for participants receiving roxadustat was allowed if all of the following criteria were met: The participant's Hb level had not responded adequately to roxadustat following two consecutive dose increases or reached the maximum dose limit, and participant's ferritin was \< 100 ng/mL (\< 220 pmol/L) or TSAT \< 20%, or the participant was intolerant of oral iron therapy. For participants treated with epoetin alfa or darbepoetin alfa, IV iron supplementation was given according to standard of care.

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

ASP1517 FG-4592 Eprex Aranesp

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

FibroGen

INDUSTRY

Sponsor Role collaborator

Astellas Pharma Europe B.V.

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Study Physician

Role: STUDY_DIRECTOR

Astellas Pharma Europe B.V.

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Site BE32004

Brussels, Flemish Brabant, Belgium

Site Status

Site BE32001

Aalst, , Belgium

Site Status

Site BE32019

Antwerp, , Belgium

Site Status

Site BE32002

Antwerp, , Belgium

Site Status

Site BE32012

Baudour, , Belgium

Site Status

Site BE32017

Bonheiden, , Belgium

Site Status

Site BE32003

Leuven, , Belgium

Site Status

Site BE32013

Liège, , Belgium

Site Status

Site BE32011

Roeselare, , Belgium

Site Status

Site BG35925

Blagoevgrad, , Bulgaria

Site Status

Site BG35931

Haskovo, , Bulgaria

Site Status

Site BG35915

Pleven, , Bulgaria

Site Status

Site BG35909

Plovdiv, , Bulgaria

Site Status

Site BG35919

Plovdiv, , Bulgaria

Site Status

Site BG35920

Rousse, , Bulgaria

Site Status

Site BG35938

Shumen, , Bulgaria

Site Status

Site BG35924

Sofia, , Bulgaria

Site Status

Site BG35906

Sofia, , Bulgaria

Site Status

Site BG35921

Sofia, , Bulgaria

Site Status

Site BG35907

Stara Zagora, , Bulgaria

Site Status

Site BG35916

Varna, , Bulgaria

Site Status

Site BG35918

Varna, , Bulgaria

Site Status

Site BG35903

Veliko Tarnovo, , Bulgaria

Site Status

Site BG35937

Yambol, , Bulgaria

Site Status

Site HR38509

Zagreb, City of Zagreb, Croatia

Site Status

Site HR38508

Čakovec, , Croatia

Site Status

Site HR38505

Karlovac, , Croatia

Site Status

Site HR38507

Osijek, , Croatia

Site Status

Site HR38506

Rijeka, , Croatia

Site Status

Site HR38504

Slavonski Brod, , Croatia

Site Status

Site HR38501

Zadar, , Croatia

Site Status

Site CZ42008

Liberec, , Czechia

Site Status

Site CZ42021

Prague, , Czechia

Site Status

Site CZ42015

Rakovník, , Czechia

Site Status

Site FR33005

Amiens, , France

Site Status

Site FR33010

La Tronche, , France

Site Status

Site FR33007

Saint Priez En Jarez, , France

Site Status

Site FR33055

Saint-Ouen, , France

Site Status

Site FR33056

Valenciennes, , France

Site Status

Site GE99503

Tbilisi, , Georgia

Site Status

Site GE99504

Tbilisi, , Georgia

Site Status

Site GE99508

Tbilisi, , Georgia

Site Status

Site DE49056

Dormagen, North Rhine-Westphalia, Germany

Site Status

Site DE49067

Berlin, , Germany

Site Status

Site DE49073

Cloppenburg, , Germany

Site Status

Site DE49008

Dresden, , Germany

Site Status

Site DE49054

Düsseldorf, , Germany

Site Status

Site DE49020

Frankfurt am Main, , Germany

Site Status

Site DE49065

Hamburg, , Germany

Site Status

Site DE49075

Heilbronn, , Germany

Site Status

Site DE49001

Kaiserslautern, , Germany

Site Status

Site DE49070

München, , Germany

Site Status

Site DE49002

Solingen, , Germany

Site Status

Site DE49071

Villingen-Schwenningen, , Germany

Site Status

Site HU36033

Baja, , Hungary

Site Status

Site HU36036

Esztergom, , Hungary

Site Status

Site HU36031

Győr, , Hungary

Site Status

Site HU36026

Kaposvár, , Hungary

Site Status

Site HU36027

Kistarcsa, , Hungary

Site Status

Site HU36032

Pécs, , Hungary

Site Status

Site HU36035

Pécs, , Hungary

Site Status

Site HU36034

Salgótarján, , Hungary

Site Status

Site HU36004

Szeged, , Hungary

Site Status

Site HU36046

Székesfehérvár, , Hungary

Site Status

Site HU36006

Szombathely, , Hungary

Site Status

Site HU36003

Zalsaegerszeg, , Hungary

Site Status

Site IT39028

Prato, Frazione Di Galciana, Italy

Site Status

Site IT39039

Cremona, Lombardy, Italy

Site Status

Site IT39014

Mestre, Venezia, Italy

Site Status

Site IT39010

Brescia, , Italy

Site Status

Site IT39008

Lecco, , Italy

Site Status

Site IT39006

Milan, , Italy

Site Status

Site IT39037

Modena, , Italy

Site Status

Site IT39022

Padua, , Italy

Site Status

Site IT39036

Pavia, , Italy

Site Status

Site IT39005

Roma, , Italy

Site Status

Site IT39035

Torino, , Italy

Site Status

Site IT39032

Trieste, , Italy

Site Status

Site PL48002

Katowice, , Poland

Site Status

Site PL48001

Krakow, , Poland

Site Status

Site PL48013

Szczecin, , Poland

Site Status

Site PL48005

Warsaw, , Poland

Site Status

Site PL48006

Wroclaw, , Poland

Site Status

Site PL48009

Wroclaw, , Poland

Site Status

Site PL48014

Zamość, , Poland

Site Status

Site PT35121

Almada, , Portugal

Site Status

Site PT35127

Aveiro, , Portugal

Site Status

Site PT35139

Cascais, , Portugal

Site Status

Site PT35117

Faro, , Portugal

Site Status

Site PT35128

Gaeiras, , Portugal

Site Status

Site PT35114

Leiria, , Portugal

Site Status

Site PT35102

Porto, , Portugal

Site Status

Site PT35122

Setúbal, , Portugal

Site Status

Site RO40018

Bucharest, , Romania

Site Status

Site RO40003

Bucharest, , Romania

Site Status

Site RO40015

Bucharest, , Romania

Site Status

Site RO40019

Bucharest, , Romania

Site Status

Site RO40004

Oradea, , Romania

Site Status

Site RU70008

Kaluga, , Russia

Site Status

Site RU70051

Moscow, , Russia

Site Status

Site RU70005

Moscow, , Russia

Site Status

Site RU70003

Nizhny Novgorod, , Russia

Site Status

Site RU70004

Omsk, , Russia

Site Status

Site RU70014

Rostov-on-Don, , Russia

Site Status

Site RU70072

Saint Petersburg, , Russia

Site Status

Site RU70011

Saint Petersburg, , Russia

Site Status

Site RU70002

Saint Petersburg, , Russia

Site Status

Site RU70030

Saint Petersburg, , Russia

Site Status

Site RU70050

Saint Petersburg, , Russia

Site Status

Site RU70006

Smolensk, , Russia

Site Status

Site RU70037

Volgograd, , Russia

Site Status

Site RU70001

Yaroslavl, , Russia

Site Status

Site RS38102

Belgrade, , Serbia

Site Status

Site RS38105

Belgrade, , Serbia

Site Status

Site RS38120

Belgrade, , Serbia

Site Status

Site RS38104

Belgrade, , Serbia

Site Status

Site RS38117

Kruševac, , Serbia

Site Status

Site RS38101

Niš, , Serbia

Site Status

Site RS38116

Zrenjanin, , Serbia

Site Status

Site SK42102

Košice, , Slovakia

Site Status

Site SK42119

Levice, , Slovakia

Site Status

Site SK42120

Lučenec, , Slovakia

Site Status

Site SK42113

Púchov, , Slovakia

Site Status

Site SK42116

Senica, , Slovakia

Site Status

Site ES34041

Santiago de Compostela, A Coruna, Spain

Site Status

Site ES34009

El Ejido, Almeria, Spain

Site Status

Site ES34010

Alcorcón, Madrid, Spain

Site Status

Site ES34030

Majadahonda, Madrid, Spain

Site Status

Site ES34011

Galdakao, Vizcaya, Spain

Site Status

Site ES34002

Badalona-Barcelona, , Spain

Site Status

Site ES34008

Barcelona, , Spain

Site Status

Site ES34006

Barcelona, , Spain

Site Status

Site ES34017

Jaén, , Spain

Site Status

Site ES34037

Madrid, , Spain

Site Status

Site ES34052

Valencia, , Spain

Site Status

Site GB44087

Brighton, EastSussex, United Kingdom

Site Status

Site GB44011

Canterbury, Kent, United Kingdom

Site Status

Site GB44080

Stoke-on-Trent, Staffordshire, United Kingdom

Site Status

Site GB44008

Cambridge, , United Kingdom

Site Status

Site GB44010

Hull, , United Kingdom

Site Status

Site GB44081

Leicester, , United Kingdom

Site Status

Site GB44079

Liverpool, , United Kingdom

Site Status

Site GB44001

Swansea, , United Kingdom

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Belgium Bulgaria Croatia Czechia France Georgia Germany Hungary Italy Poland Portugal Romania Russia Serbia Slovakia Spain United Kingdom

References

Explore related publications, articles, or registry entries linked to this study.

Hamano T, Yamaguchi Y, Goto K, Martin S, Jiletcovici A, Dellanna F, Akizawa T, Barratt J. Risk Factors for Thromboembolic Events in Patients With Dialysis-Dependent CKD: Pooled Analysis of Four Global Roxadustat Phase 3 Trials. Adv Ther. 2024 Apr;41(4):1553-1575. doi: 10.1007/s12325-023-02728-2. Epub 2024 Feb 16.

Reference Type DERIVED
PMID: 38363466 (View on PubMed)

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.

Reference Type DERIVED
PMID: 36005278 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

Access external resources that provide additional context or updates about the study.

https://astellasclinicalstudyresults.com/study.aspx?ID=364

Link to results on Astellas Clinical Study Results website

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

2013-001497-16

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

1517-CL-0613

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Treatment Response in Dialysis Anaemia
NCT02707757 COMPLETED PHASE4