Roxadustat in the Treatment of Anemia in Chronic Kidney Disease (CKD) Patients, Not on Dialysis, in Comparison to Darbepoetin Alfa

NCT02021318 | Completed Phase 3 Results DMC

• 2 other identifiers: 1517-CL-06102013-000951-42
• Study Type: interventional
• Target: 616
• Locations: 25 countries
• Sites: 121

Brief Summary

The primary objective of this study was to evaluate the efficacy of roxadustat compared to darbepoetin alfa in the treatment of anemia in nondialysis-dependent chronic kidney disease (NDD CKD) participants.

Conditions

Anemia in Chronic Kidney Disease in Non-dialysis Patients

Keywords

Non-dialysis; Roxadustat; ASP1517; Chronic Kidney Disease (CKD); Anemia; Hemoglobin

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With a Hb Response to Treatment at Two Consecutive Visits During the First 24 Weeks of Treatment Without Rescue Therapy

  Hb response was measured as Yes or No. Response Yes (responders) was defined as: Hb ≥11.0 g/dL and Hb change from baseline by ≥ 1.0 g/dL, for participants with baseline Hb \> 8.0 g/dL; or Hb change from baseline by ≥ 2.0 g/dL, for participants with baseline Hb ≤ 8.0 g/dL at two consecutive visits with available data separated at least 5 days during the first 24 weeks of treatment without having received rescue therapy (red blood cell \[RBC\] transfusion for all participants or darbepoetin for roxadustat treated participant).

  Baseline to week 24

Secondary Outcomes (60)

• Change From Baseline in Hb to the Average Hb of Weeks 28 to 36 Without Rescue Therapy Within 6 Weeks Prior to and During This 8-Week Evaluation Period

  Baseline and weeks 28 to 36

• Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) to the Average LDL-C of Weeks 12 to 28

  Baseline and weeks 12 to 28

• Time to First Intravenous Iron Use

  Weeks 6, 12, 18, 24, 30 and 36

• Change From Baseline in Short Form-36 (SF-36) Physical Functioning (PF) Sub-Score to the Average PF Sub Score in Weeks 12 to 28

  Baseline and weeks 12 to 28

• Change From Baseline in SF-36 Vitality (VT) Sub-Score to the Average VT Sub-Score in Weeks 12 to 28

  Baseline and weeks 12 to 28

Study Arms (2)

Roxadustat

EXPERIMENTAL

Participants received roxadustat orally according to the tiered weight-based approach, with starting dose of 70 mg (milligram) given thrice weekly (TIW) to participants weighing up to 70 kg (kilogram) and 100 mg given TIW to participants weighing more than 70 kg. Dose-titration was performed based upon regular measurement of Hb levels until participants achieved central Hb value of ≥ 11.0 g/dL (gram per deciliter) and Hb increase from baseline of ≥ 1.0 g/dL at two consecutive study visits, separated by at least 5 days. Once target Hb level was reached participants entered maintenance period during which roxadustat dosage was adjusted every 4 weeks to maintain participants Hb level within the target range of 10.0 g/dL and 12.0 g/dL. Participants received roxadustat up to a maximum of 104 weeks.

Drug: Roxadustat

Darbepoetin alfa

ACTIVE COMPARATOR

Participants received initial dose of darbepoetin alfa based upon the weight (either 0.45 μg/kg (microgram per kilogram), as a single subcutaneous or intravenous (IV) injection once weekly or 0.75 μg/kg, as a single subcutaneous injection once every 2 weeks) as per European Summary of Product Characteristics (EU SmPC) along with IV iron supplementation according to the standard of care. Dose-adjustment was performed based upon regular measurement of Hb levels until participants achieved central Hb value of ≥ 11.0 g/dL and Hb increase from baseline of ≥ 1.0 g/dL at two consecutive study visits, separated by at least 5 days. Once target Hb level was reached participants entered maintenance period during which darbepoetin alfa dosage was adjusted every 4 weeks to maintain participants Hb level within the target range of 10.0 g/dL and 12.0 g/dL. Participants received darbepoetin alfa for up to a maximum of 104 weeks.

Drug: Darbepoetin alfa

Interventions

Roxadustat DRUG

Oral tablet.

Also known as: ASP1517

Roxadustat

Darbepoetin alfa DRUG

Subcutaneous or intravenous injection.

Also known as: Aranesp

Darbepoetin alfa

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject has a diagnosis of CKD, with Kidney Disease Outcomes Quality Initiative (KDOQI) Stage 3, 4 or 5, not on dialysis; with an Estimated Glomerular Filtration Rate (eGFR) \<60 mL/min/1.73 m\^2 estimated using the abbreviated 4-variable Modification of Diet in Renal Disease (MDRD) equation.
• The mean of the subject's two most recent (prior to randomization) Hb values during the screening period, obtained at least 4 days apart, must be less than or equal to 10.5 g/dL, with a difference of less than or equal to 1.0 g/dL. The last Hb value must be within 10 days prior to randomization.
• Subject is deemed suitable for treatment with Erythropoiesis Stimulating Agent (ESA) using the criteria specified in the Kidney Disease Improving Global Outcomes (KDIGO) 2012 recommendation considering the rate of fall of Hb concentration, prior response to iron therapy, the risk of needing a transfusion, the risks related to ESA therapy and the presence of symptoms attributable to anemia.
• Subject has a serum folate level greater than or equal to lower limit of normal (LLN) at screening.
• Subject has a serum vitamin B12 level greater than or equal to LLN at screening.
• Subject's alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are less than or equal to 3 x upper limit of normal (ULN), and total bilirubin (TBL) is less than or equal to 1.5 x ULN.
• Subject's body weight is 45.0 kg to a maximum of 160.0 kg.
• Male subject must not donate sperm starting from screening, throughout the study period and up to 12 weeks after final study drug administration.

You may not qualify if:

• Subject has received any Erythropoiesis Stimulating Agent (ESA) treatment within 12 weeks prior to randomization.
• Subject has received any dose of IV iron within 6 weeks prior to randomization.
• Subject has received a Red Blood Cell (RBC) transfusion within 8 weeks prior to randomization.
• Subject has a known history of myelodysplastic syndrome or multiple myeloma.
• Subject 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).
• Subject has a known hemosiderosis, hemochromatosis, coagulation disorder, or hypercoagulable condition.
• Subject has a known chronic inflammatory disease that could impact erythropoiesis (e.g., systemic lupus erythematosus, rheumatoid arthritis, celiac disease) even if it is currently in remission.
• Subject is anticipated to undergo elective surgery that is expected to lead to significant blood loss during the study period or anticipated elective coronary revascularization.
• Subject has active or chronic gastrointestinal bleeding.
• Subject has received any prior treatment with roxadustat or a Hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI).
• Subject has been treated with iron-chelating agents within 4 weeks prior to randomization.
• Subject has a history of chronic liver disease (e.g., cirrhosis or fibrosis of the liver).
• Subject has known New York Heart Association Class III or IV congestive heart failure.
• Subject has had a myocardial infarction, acute coronary syndrome, stroke, seizure, or a thrombotic/thromboembolic event (e.g., deep vein thrombosis or pulmonary embolism) within 12 weeks prior to randomization.
• Subject has one or more contraindications for treatment with darbepoetin alfa:

Sponsors & Collaborators

• Astellas Pharma Europe B.V.: lead
• Kyntra Bio: collaborator

Study Sites (125)

Site AT43009

Vienna, Austria

Location

Site BY37503

Brest, 224027, Belarus

Location

Site BY37501

Grodno, 230017, Belarus

Location

Site BY37506

Minsk, 220036, Belarus

Location

Site BY37507

Minsk, 220116, Belarus

Location

Site BY37505

Minsk, 223040, Belarus

Location

Site BY37502

Vitebsk, 210037, Belarus

Location

Site BG35907

Sofia, 1113, Bulgaria

Location

Site BG35927

Sofia, 1709, Bulgaria

Location

Site BG35916

Varna, 9000, Bulgaria

Location

Site HR38505

Karlovac, 47000, Croatia

Location

Site HR38504

Slavonski Brod, 35000, Croatia

Location

Site HR38510

Zagreb, 10 000, Croatia

Location

Site HR38502

Zagreb, 10000, Croatia

Location

Site HR38509

Zagreb, 10000, Croatia

Location

Site CZ42018

Nový Jičín, CZ, 741 01, Czechia

Location

Site CZ42008

Liberec, 46063, Czechia

Location

Site CZ42021

Prague, Czechia

Location

Site FI35810

Helsinki, 290, Finland

Location

Site FR33004

Avignon, 84900, France

Location

Site FR33009

Colmar, 68024, France

Location

Site FR33010

Grenoble, France

Location

Site FR33062

Limoges, 87042, France

Location

Site FR33012

Lyon, 69437, France

Location

Site FR33007

Saint-Priest-en-Jarez, 42270, France

Location

Site GE99503

Tbilisi, 144, Georgia

Location

Site GE99504

Tbilisi, 144, Georgia

Location

Site GE99502

Tbilisi, 159, Georgia

Location

Site DE49073

Cloppenburg, 49661, Germany

Location

Site DE49054

Düsseldorf, 40210, Germany

Location

Site DE49065

Hamburg, 23397, Germany

Location

Site DE49075

Heilbronn, 74076, Germany

Location

Site DE49057

Hoyerswerda, 02977, Germany

Location

Site HU36028

Budapest, 1097, Hungary

Location

Site HU36029

Budapest, Hungary

Location

Site HU36027

Kistarcsa, 2143, Hungary

Location

Site HU36008

Pécs, H 7624, Hungary

Location

Site HU36046

Velence, Hungary

Location

Site IE35301

Cork, Ireland

Location

Site IL97202

Be’er Ya‘aqov, 70300, Israel

Location

Site IL97215

Haifa, 34362, Israel

Location

Site LV37101

Riga, LV-1002, Latvia

Location

Site LV37104

Ventspils, LV-3601, Latvia

Location

Site ME38202

Nikšić, 81400, Montenegro

Location

Site ME38201

Podgorica, 81000, Montenegro

Location

Site NL31005

Utrecht, 3584 CX, Netherlands

Location

Site MK38901

Skopje, 1000, North Macedonia

Location

Site MK38903

Struga, 6330, North Macedonia

Location

Site PL48001

Krakow, 31-559, Poland

Location

Site PL48066

Puławy, 24-100, Poland

Location

Site PL48013

Szczecin, 70-111, Poland

Location

Site PL48007

Tarnów, 33-100, Poland

Location

Site PL48004

Warsaw, 04-749, Poland

Location

Site PL48009

Wroclaw, Poland

Location

Site PL48059

Zamość, 22-400, Poland

Location

Site PT35120

Almada, 2801-951, Portugal

Location

Site PT35131

Braga, 4710-243, Portugal

Location

Site PT35112

Carnaxide, 2795-523, Portugal

Location

Site PT35119

Evora, 7000-811, Portugal

Location

Site PT35118

Lisbon, 1069-166, Portugal

Location

Site PT35133

Matosinhos Municipality, 4464-513, Portugal

Location

Site PT35122

Setúbal, 2910-446, Portugal

Location

Site PT35132

Vila Nova de Gaia, 4434-502, Portugal

Location

Site RO40012

Bucharest, 10825, Romania

Location

Site RO40003

Bucharest, 11234, Romania

Location

Site RO40021

Bucharest, 22328, Romania

Location

Site RO40004

Oradea, 410469, Romania

Location

Site RU70024

Chelyabinsk, 454047, Russia

Location

Site RU70054

Irkutsk, 664079, Russia

Location

Site RU70047

Moscow, 119992, Russia

Location

Site RU70006

Moscow, 125284, Russia

Location

Site RU70003

Nizhny Novgorod, 603032, Russia

Location

Site RU70004

Omsk, 644112, Russia

Location

Site RU70014

Rostov-on-Don, 344029, Russia

Location

Site RU70011

Saint Petersburg, 196247, Russia

Location

Site RU70002

Saint Petersburg, 197089, Russia

Location

Site RU70060

Saratov, 410039, Russia

Location

Site RU70057

Yaroslavl, 150000, Russia

Location

Site RU70001

Yaroslavl, 150062, Russia

Location

Site RS38102

Belgrade, 11000, Serbia

Location

Site RS38105

Belgrade, 11000, Serbia

Location

Site RS38103

Belgrade, 11080, Serbia

Location

Site RS38104

Belgrade, Serbia

Location

Site RS38117

Kruševac, 37000, Serbia

Location

Site RS38101

Niš, 11070, Serbia

Location

Site SK42102

Košice, 04001, Slovakia

Location

Site SK42109

Košice, 04001, Slovakia

Location

Site SK42113

Púchov, 02001, Slovakia

Location

Site SK42116

Senica, 905 01, Slovakia

Location

Site SI38615

Jesenice, SI-4270, Slovenia

Location

Site SI38603

Maribor, 2000, Slovenia

Location

Site SI38619

Slovenj Gradec, SI 2380, Slovenia

Location

Site SI38609

Šempeter pri Gorici, 5290, Slovenia

Location

Site ES34049

Ferrol, A Coruna, 15405, Spain

Location

Site ES34026

Barcelona, 08907, Spain

Location

Site ES34039

Córdoba, 14004, Spain

Location

Site ES34054

Girona, 17007, Spain

Location

Site ES34017

Jaén, 23007, Spain

Location

Site ES34037

Madrid, 28046, Spain

Location

Site ES34010

Madrid, 28922, Spain

Location

Site ES34030

Majadahonda, 28222, Spain

Location

Site ES34041

Santiago de Compostela, 15706, Spain

Location

Site UA38009

Lviv, Lvivska, 79010, Ukraine

Location

Site UA38021

Cherkasy, 18009, Ukraine

Location

Site UA38006

Dnipropetrovsk, 49005, Ukraine

Location

Site UA38016

Ivano-Frankivsk, 76018, Ukraine

Location

Site UA38011

Kharkiv, 61103, Ukraine

Location

Site UA38017

Kiev, 4053, Ukraine

Location

Site UA38007

Mykolaiv, Ukraine

Location

Site UA38008

Odesa, 6500, Ukraine

Location

Site UA38001

Ternopil, 46002, Ukraine

Location

Site UA38018

Uzhhorod, 88018, Ukraine

Location

Site GB44098

Dorchester, Dorset, DT1 2JY, United Kingdom

Location

Site GB44064

Birmingham, B9 5SS, United Kingdom

Location

Site GB44099

Dartford, DA2 8DA, United Kingdom

Location

Site GB44102

Kings Lynn, PE30 4ET, United Kingdom

Location

Site GB44081

Leicester, LE5 4PW, United Kingdom

Location

Site GB44086

London, E1 1BB, United Kingdom

Location

Site GB44006

London, SE5 9RS, United Kingdom

Location

Site GB44082

London, SW17 0QT, United Kingdom

Location

Site GB44097

Nottingham, NG5 1PB, United Kingdom

Location

Site GB44100

Orpington, BR6 8ND, United Kingdom

Location

Site GB44101

Preston, PR2 9HT, United Kingdom

Location

Site GB44080

Stoke-on-Trent, ST4 6QG, United Kingdom

Location

Site GB44001

Swansea, SA6 6NL, United Kingdom

Location

Related Publications (2)

• Barratt J, Dellanna F, Portoles J, Choukroun G, De Nicola L, Young J, Dimkovic N, Reusch M. Safety of Roxadustat Versus Erythropoiesis-Stimulating Agents in Patients with Anemia of Non-dialysis-Dependent or Incident-to-Dialysis Chronic Kidney Disease: Pooled Analysis of Four Phase 3 Studies. Adv Ther. 2023 Apr;40(4):1546-1559. doi: 10.1007/s12325-023-02433-0. Epub 2023 Feb 7.

  PMID: 36749544 DERIVED

• 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.

  PMID: 36005278 DERIVED

Related Links

• Link to results on the Astellas Clinical Study Results website.

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Anemia

Interventions

roxadustat; Darbepoetin alfa

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Erythropoietin; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Proteins; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Clinical Trial Disclosure
• Organization: Astellas Pharma Europe B.V.

Astellas.resultsdisclosure@astellas.com

+44 (0)20 3379 8000

Study Officials

• Medical Monitor

  Astellas Pharma Europe B.V.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2013
• First Posted: December 27, 2013
• Study Start: March 12, 2014
• Primary Completion: March 23, 2018
• Study Completion: November 6, 2019
• Last Updated: November 14, 2024
• Results First Posted: March 29, 2021

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
• Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.

Locations

BU (3); FI (1); NL (1); LA (2); RO (4); SL (4); ES (9); DE (5); UA (10); IE (1); AU (1); NO (2); MO (2); CZ (3); PT (8); CR (5); GE (3); RU (12); FR (6); GB (13); IL (2); HU (5); SE (6); PL (7); BE (6)