Roxadustat in the Treatment of Anemia in Chronic Kidney Disease Patients Not Requiring Dialysis
ALPS
A Phase 3, Randomized, Double-Blind, Placebo Controlled Study of the Efficacy and Safety of Roxadustat for the Treatment of Anemia in Chronic Kidney Disease Patients Not on Dialysis
2 other identifiers
interventional
594
20 countries
130
Brief Summary
This study was conducted to treat anemia in patients with chronic kidney disease. Anemia is a reduced number of red blood cells or hemoglobin. Hemoglobin is important for the transport of oxygen in your blood. The purpose of the study was to see if Roxadustat is both effective and safe as a treatment for anemia in patients with chronic kidney disease.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Sep 2013
Typical duration for phase_3
130 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 25, 2013
CompletedFirst Posted
Study publicly available on registry
June 27, 2013
CompletedStudy Start
First participant enrolled
September 3, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
November 1, 2017
CompletedResults Posted
Study results publicly available
December 17, 2020
CompletedNovember 14, 2024
October 1, 2024
4.2 years
June 25, 2013
October 8, 2020
October 29, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Percentage of Participants With a Hemoglobin (Hb) Response to Treatment at Two Consecutive Visits During the First 24 Weeks of Treatment Without Rescue Therapy Prior to Hb Response
Hemoglobin (Hb) response was measured as Yes or No. Response Yes (responders) was defined as: Hb ≥11.0 g/dL and Hb increase from baseline by ≥ 1.0 g/dL, for participants with baseline Hb \> 8.0 g/dL; or Hb increase 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, erythropoiesis-stimulating agent (ESA), or intravenous (IV) iron prior to Hb response. This was the primary efficacy endpoint for EU (EMA).
Baseline to week 24
Hb Change From Baseline (BL) to the Average Hb in Weeks 28-52 Regardless of Rescue Therapy
The change from baseline to the average Hb values across weeks 28 to 52 without having received rescue therapy. The Hb values from visit windows at weeks 28, 32, 36, 40, 44, 48 and 52 were used for the calculation of the average of weeks 28 to 52. This was the primary efficacy endpoint for US (FDA).
Baseline and weeks 28 to 52
Secondary Outcomes (51)
Hb Change From BL to the Average Hb in Weeks 28-36 Without Having Received Rescue Therapy Within 6 Weeks Prior to and During 8-Week Evaluation Period
Baseline and weeks 28 to 36
Change From BL in Low-Density Lipoprotein (LDL) Cholesterol (Regardless of Fasting Status) to the Average LDL Cholesterol of Weeks 12 to 28
Baseline and weeks 12 to 28
Time to First Use of Rescue Therapy (Composite of Red Blood Cell (RBC) Transfusions, Erythropoiesis-stimulating Agent (ESA) Use, and Intravenous (IV) Iron)
Baseline to week 104 (End of Treatment [EOT])
Change From BL in Short Form (SF)-36 Vitality (VT) Sub-score to the Average VT Sub-score of Weeks 12 to 28
Baseline and weeks 12 to 28
Change From BL in SF-36 Physical Functioning (PF) Sub-score to the Average PF Sub-score of Weeks 12 to 28
Baseline and weeks 12 to 28
- +46 more secondary outcomes
Study Arms (2)
Roxadustat
EXPERIMENTALParticipants received roxadustat according to the tiered weight-based approach, with starting doses of 70 mg given thrice weekly (TIW) to participants weighing up to 70 kg 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 and Hb increase from baseline (BL) 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 for at least 52 weeks up to a maximum of 104 weeks.
Placebo
PLACEBO COMPARATORParticipants received matching placebo according to the tiered weight-based approach, with starting doses of 70 mg given thrice weekly (TIW) to participants weighing up to 70 kg 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 and Hb increase from baseline (BL) 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 matching placebo for at least 52 weeks up to a maximum of 104 weeks.
Interventions
Roxadustat was administered initially according to the tiered weight-based dosing, where participants with weight from ≥ 45 to ≤ 70 kg received 70 mg and participants with \> 70 to ≤ 160 kg received 100 mg of roxadustat. Dose-titration based upon regular measurement of Hb levels was performed until participants achieved central Hb value of ≥ 11.0 g/dL and Hb increase from baseline (BL) 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.
Placebo was administered initially according to the tiered weight-based dosing, where participants with weight from ≥ 45 to ≤ 70 kg received 70 mg and participants with \> 70 to ≤ 160 kg received 100 mg of roxadustat. Dose-titration based upon regular measurement of Hb levels was performed until participants achieved central Hb value of ≥ 11.0 g/dL and Hb increase from baseline (BL) 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.
Eligibility Criteria
You may qualify if:
- Participant has a diagnosis of chronic kidney disease, with Kidney Disease Outcomes Quality Initiative (KDOQI) Stage 3, 4 or 5, not receiving 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 Participant's three most recent Hb values during the Screening period, obtained at least 4 days apart, must be less than or equal to 10.0 g/dL, with a difference of less than or equal to 1.0 g/dL between the highest and the lowest values. The last Hb value must be within 10 days prior to randomization.
- Participant has a ferritin level greater than or equal to 30 ng/mL (greater than or equal to 67.4 pmol/L) at screening.
- Participant has a transferrin saturation (TSAT) level greater than or equal to 5% at screening.
- Participant has a serum folate level greater than or equal to lower limit of normal at screening.
- Participant has a serum vitamin B12 level greater than or equal to lower limit of normal at screening.
- Participant's alanine aminotransferase (ALT), aspartate aminotransferase (AST) levels 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.
- Participant's body weight is 45.0 kg up to a maximum of 160.0 kg.
You may not qualify if:
- Participant has received any ESA treatment within 12 weeks prior to randomization.
- Participant has had more than one dose of IV iron within 12 weeks prior to randomization.
- Participant has received a RBC transfusion within 8 weeks prior to randomization.
- Participant has a known history of myelodysplastic syndrome or multiple myeloma.
- 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 CKD.
- Participant has a known hemosiderosis, hemochromatosis, coagulation disorder, or hypercoagulable condition.
- Participant has chronic inflammatory disease that could impact erythropoiesis (e.g., systemic lupus erythematosus, rheumatoid arthritis, celiac disease) even if it is currently in remission.
- Participant is anticipated to have elective surgery that is expected to lead to significant blood loss or anticipated elective coronary revascularization.
- Participant has active or chronic gastrointestinal bleeding.
- Participant has received any prior treatment with roxadustat or a hypoxia-inducible factor Prolyl Hydroxylase Inhibitor (HIF-PHI).
- Participant has been treated with iron-chelating agents within 4 weeks prior to randomization.
- Participant has a history of chronic liver disease (e.g., cirrhosis or fibrosis of the liver)
- Participant has a known New York Heart Association Class III or Intravenous (IV) congestive heart failure.
- Participant has had a myocardial infarction, acute coronary syndrome, stroke, seizure, or a thrombotic/thromboembolic event (e.g., pulmonary embolism) within 12 weeks prior to randomization.
- Uncontrolled hypertension or two or more blood pressure (BP) values of systolic BP (SBP) greater than or equal to 160 mmHg or diastolic BP (DBP) greater than or equal to 95 mmHg confirmed by repeat measurement within 2 weeks prior to randomization.
- +9 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Astellas Pharma Europe B.V.lead
- Kyntra Biocollaborator
Study Sites (138)
Site BY37503
Brest, 224027, Belarus
Site BY37501
Grodno, 230017, Belarus
Site BY37504
Homyel, 246027, Belarus
Site BY37506
Minsk, 220036, Belarus
Site BY37507
Minsk, 220116, Belarus
Site BY37505
Minsk, 223040, Belarus
Site BY37502
Vitebsk, 210037, Belarus
Site BE32004
Brussels, Flemish Brabant, 1200, Belgium
Site BE32002
Antwerp, 2060, Belgium
Site BE32012
Baudour, 7331, Belgium
Site BE32017
Bonheiden, 2820, Belgium
Site BE32014
Ieper, 8900, Belgium
Site BE32013
Liège, 4000, Belgium
Site BG35923
Pazardzhik, 4400, Bulgaria
Site BG35906
Sofia, 1431, Bulgaria
Site BG35908
Sofia, 1431, Bulgaria
Site BG35910
Sofia, 1431, Bulgaria
Site BG35907
Stara Zagora, 6000, Bulgaria
Site BG35916
Varna, 9000, Bulgaria
Site BG35903
Veliko Tarnovo, 5000, Bulgaria
Site CO57007
Barranquilla, Colombia
Site CO57008
Barranquilla, Colombia
Site CO57002
Pereira, Colombia
Site DO17101
La Fe Santo Domingo, 5072, Dominican Republic
Site DO17102
Santiago de los Caballeros, 51000, Dominican Republic
Site DO17104
Santo Domingo, 10124, Dominican Republic
Site DO17103
Santo Domingo, 103201, Dominican Republic
Site EE37201
Tallinn, 13419, Estonia
Site GE99503
Tbilisi, 0144, Georgia
Site GE99504
Tbilisi, 0144, Georgia
Site GE99502
Tbilisi, 0159, Georgia
Site GR30003
Heraklion, 71409, Greece
Site GR30002
Pátrai, 26504, Greece
Site GR30001
Thessaloniki, 54642, Greece
Site GT50209
Chiquimula, 01001, Guatemala
Site GT50205
Guatemala City, 01010, Guatemala
Site GT50206
Guatemala City, 01010, Guatemala
Site GT50203
Guatemala City, 01014, Guatemala
Site GT50202
Guatemala City, AP 01015, Guatemala
Site GT50208
Guatemala City, CP 01001, Guatemala
Site GT50207
Guatemala City, CP 01010, Guatemala
Site GT50201
Guatemala City, CP 01016, Guatemala
Site HU36029
Budapest, H-1036, Hungary
Site HU36025
Győr, 9002, Hungary
Site HU36026
Kaposvár, H 7400, Hungary
Site HU36027
Kistarcsa, 2143, Hungary
Site HU36008
Pécs, H 7624, Hungary
Site HU36028
Szent, H-1097, Hungary
Site HU36003
Zalsaegerszeg, 8900, Hungary
Site IT39001
Bari, 70124, Italy
Site IT39008
Lecco, 23900, Italy
Site IT39006
Milan, 20162, Italy
Site IT39037
Modena, 41124, Italy
Site IT39036
Pavia, 27100, Italy
Site PA50703
Colón, 0302-00504 Z.L., Panama
Site PA50701
Panama City, Panama
Site PE51001
Iquitos, 16001, Peru
Site PE51002
Trujillo, 13001, Peru
Site PL48001
Krakow, Malopolska, 31-559, Poland
Site PL48002
Katowice, 40 027, Poland
Site PL48012
Lodz, 90549, Poland
Site PL48008
Lodz, 92-213, Poland
Site PL48057
Nowy Tomyśl, 64-300, Poland
Site PL48013
Szczecin, 70-111, Poland
Site PL48007
Tarnów, 33 100, Poland
Site PL48005
Warsaw, 02-507, Poland
Site PL48004
Warsaw, 04 749, Poland
Site PL48006
Wroclaw, 50-556, Poland
Site PL48014
Zamość, 20-400, Poland
Site RO40005
Timișoara, Timiș County, 300736, Romania
Site RO40001
Brasov, 500366, Romania
Site RO40021
Bucharest, 022328, Romania
Site RO40012
Bucharest, 10825, Romania
Site RO40003
Bucharest, 22328, Romania
Site RO40004
Oradea, 410469, Romania
Site RU70024
Chelyabinsk, 454047, Russia
Site RU70054
Irkutsk, 664079, Russia
Site RU70008
Kaluga, 248007, Russia
Site RU70051
Moscow, 119992, Russia
Site RU70007
Moscow, 123182, Russia
Site RU70005
Moscow, 125284, Russia
Site RU70048
Moscow, 129301, Russia
Site RU70047
Moscow, 129327, Russia
Site RU70003
Nizhny Novgorod, 603032, Russia
Site RU70004
Omsk, 644112, Russia
Site RU70043
Petrozavodsk, 185019, Russia
Site RU70014
Rostov-on-Don, 344029, Russia
Site RU70022
Saint Petersburg, 192242, Russia
Site RU70045
Saint Petersburg, 194354, Russia
Site RU70011
Saint Petersburg, 196247, Russia
Site RU70002
Saint Petersburg, 197089, Russia
Site RU70060
Saratov, 410039, Russia
Site RU70006
Smolensk, 214006, Russia
Site RU70057
Yaroslavl, 150045, Russia
Site RU70001
Yaroslavl, 150062, Russia
Site RS38102
Belgrade, 11000, Serbia
Site RS38104
Belgrade, 11000, Serbia
Site RS38105
Belgrade, 11000, Serbia
Site RS38103
Belgrade, 11080, Serbia
Site RS38117
Kruševac, 37000, Serbia
Site RS38101
Niš, 18000, Serbia
Site RS38116
Zrenjanin, 23000, Serbia
Site ZA27001
Observatory, Cape Town, 7925, South Africa
Site ZA27004
Bloemfontein, Free State, 9324, South Africa
Site ZA27002
Durban, KwaZulu-Natal, 4001, South Africa
Site ZA27008
Durban, 4001, South Africa
Site ZA27006
Parow, 7500, South Africa
Site ZA27007
Port Elizabeth, 6001, South Africa
Site ES34010
Alcorcón, Madrid, 28922, Spain
Site ES34011
Galdakao, Vizcaya, 48960, Spain
Site ES34002
Badalona-Barcelona, 8916, Spain
Site ES34003
Barcelona, 08003, Spain
Site ES34006
Barcelona, 08035, Spain
Site ES34007
Ciudad Real, 13005, Spain
Site TR90003
Ankara, 6340, Turkey (Türkiye)
Site TR90016
Edirne, 22030, Turkey (Türkiye)
Site TR90024
Kocaeli, 41380, Turkey (Türkiye)
Site TR90020
Malatya, 44300, Turkey (Türkiye)
Site UA38009
Lviv, Lvivska, 79010, Ukraine
Site UA38021
Cherkasy, 18009, Ukraine
Site UA38003
Chernivtsi, 58002, Ukraine
Site UA38006
Dnipro, 49005, Ukraine
Site UA38016
Ivano-Frankivsk, 76018, Ukraine
Site UA38011
Kharkiv, 61103, Ukraine
Site UA38015
Kherson, 73000, Ukraine
Site UA38010
Kyiv, 01016, Ukraine
Site UA38012
Kyiv, 02125, Ukraine
Site UA38017
Kyiv, 04050, Ukraine
Site UA38007
Mykolaiv, 54058, Ukraine
Site UA38008
Odesa, 65000, Ukraine
Site UA38019
Odesa, 65026, Ukraine
Site UA38001
Ternopil, 46002, Ukraine
Site UA38018
Uzhhorod, 88018, Ukraine
Site UA38002
Zaporizhzhya, 69600, Ukraine
Site GB44008
Cambridge, CB5 8QD, United Kingdom
Site GB44001
Swansea, SA6 6NL, United Kingdom
Site GB44005
Welwyn Garden City, AL7 4HQ, United Kingdom
Site GB44004
Westcliff-on-Sea, SS0 0RY, United Kingdom
Related Publications (2)
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: 36005278DERIVEDProvenzano R, Szczech L, Leong R, Saikali KG, Zhong M, Lee TT, Little DJ, Houser MT, Frison L, Houghton J, Neff TB. Efficacy and Cardiovascular Safety of Roxadustat for Treatment of Anemia in Patients with Non-Dialysis-Dependent CKD: Pooled Results of Three Randomized Clinical Trials. Clin J Am Soc Nephrol. 2021 Aug;16(8):1190-1200. doi: 10.2215/CJN.16191020.
PMID: 34362786DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Clinical Trial Disclosure
- Organization
- Astellas Pharma Europe B.V. (APEB)
Study Officials
- STUDY CHAIR
Medical Monitor
Astellas Pharma Europe B.V.
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 25, 2013
First Posted
June 27, 2013
Study Start
September 3, 2013
Primary Completion
November 1, 2017
Study Completion
November 1, 2017
Last Updated
November 14, 2024
Results First Posted
December 17, 2020
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.
Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as products terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.