CKD Anemia in Stable Dialysis PatientsPhase 3NCT02273726

Study to Evaluate the Efficacy and Safety of Roxadustat in the Treatment of Anemia in Participants With ESRD on Stable Dialysis

A Phase 3 study testing Epoetin Alfa and Roxadustat in people with CKD Anemia in Stable Dialysis Patients, run by Kyntra Bio at 76 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The primary objective of this study is to evaluate the efficacy and safety of roxadustat compared with active control (epoetin alfa) for the maintenance treatment of anemia in participants with ESRD on dialysis. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: CKD Anemia in Stable Dialysis Patients
What is being tested?: Epoetin Alfa and Roxadustat
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 741 participants
Where: 76 sitesin 2 countries
Study dates: 15 Jan 2015to 19 Sep 2018
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Receiving dialysis for ESRD for ≥3 months. Incident dialysis participants (under Amendment 1 and 2) receiving dialysis for ESRD for ≥ 2 weeks but ≤ 4 months at the time of randomization
Participants must be on ESA for ≥ 8 weeks prior to screening; incident dialysis participants must be on ESA for ≥ 4 weeks prior to screening.
Mean of the 3 most recent central lab Hb values during the Screening Period must be ≥ 9.0 g/dL and ≤ 12.0 g/dL (for incident dialysis participants, mean of the 2 most recent Hb values must be ≥ 8.5 g/dL and ≤ 12.0 g/dL); with an absolute difference of ≤ 1.3 g/dL between the highest and the lowest value. Samples are obtained at least 4 days apart (2 days under Amendment 2) and the last Hb value must be within 10 days prior to the randomization visit
Participants with ferritin level ≥ 100 nanograms (ng)/milliliter (mL) (<100 ng/mL under Amendment 2) or transferrin saturation (TSAT) ≥ 20% (<20% under Amendment 2) at screening may qualify upon receiving iron supplement (per local standard of care)
Participants with a serum folate and Vitamin B12 ≥ lower limit of normal (LLN) (< LLN under Amendment 2) at screening may qualify upon receiving supplement (per local standard of care)
Participant's alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are ≤3x the upper limit of normal (ULN), and total bilirubin (TBL) is ≤1.5x ULN at screening
Participant's body weight is 45 kilograms (kg) to 160 kg.

Who cannot join

Participant has received an red blood cell (RBC) transfusion within 8 weeks (4 weeks under Amendment 2) prior to randomization
Participant has known history of myelodysplastic syndrome or multiple myeloma
Participant has known inherited disease such as thalassemia or sickle cell anemia or other known causes for anemia other than chronic kidney disease.
Participant has known hemosiderosis, hemochromatosis, coagulation disorder,or hypercoagulable condition
Participant has known chronic inflammatory disease that could cause anemia
Participant has anticipated surgery that is expected to cause blood loss

Show all 15Show fewer

Participant has known gastrointestinal bleeding
Participant has history of chronic liver disease (for example, chronic infectious hepatitis,chronic auto-immune liver disease,cirrhosis, or fibrosis of the liver)
Participant with New York Heart Association (NYHA) Class III or IV congestive heart failure
Participant has had a heart attack, stroke, seizure, or a thrombotic/thromboembolic event (for example, deep vein thrombosis or pulmonary embolism) within 12 weeks prior to participating in the study
Participant has uncontrolled high blood pressure within 2 weeks prior to participating in the study
Participant has a history of malignancy, except for the following: cancers determined to be cured or in remission for ≥2 years, curatively resected basal cell or squamous cell skin cancers, cervical cancer in situ, or resected colonic polyps.)
Participant is positive for human immunodeficiency virus (HIV), Hepatitis B surface antigen, or anti-hepatitis C virus antibody
Participant with prior organ transplant who experience rejection within 6 months or on high doses of immunosuppressive therapy
Participant has any of the following known untreated conditions; proliferative diabetic retinopathy, diabetic macular edema, macular degeneration or retinal vein occlusion.

Trial locations and contacts

76 sites in 2 countries.

Country

City, postcode or hospital

76 sites in 2 countries

United States74 sites

Research Center
Aiken, South Carolina, 29803
Research Center
Albany, Georgia, 31701
Research Center
Albuquerque, New Mexico, 87109
Research Center
Alexandria, Virginia, 20735
Research Center
Arlington, Texas, 76015-2368
Research Center
Brookhaven, Mississippi, 39601
Research Center
Charlotte, North Carolina, 28204
Research Center
Chula Vista, California, 91910
Research Center
Chula Vista, California, 91915
Research Center
College Point, New York, 11356
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Columbia, South Carolina, 29203
Research Center
Columbus, Mississippi, 39705
Research Center
Columbus, Ohio, 43210
Research Center
Columbus, Ohio, 43215
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Coral Springs, Florida, 33071
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Creve Coeur, Missouri, 63141
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Detroit, Michigan, 48202
Research Center
Detroit, Michigan, 48236
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Durham, North Carolina, 27704
Research Center
Edinburg, Texas, 78539
Research Center
Fort Worth, Texas, 76104
Research Center
Fort Worth, Texas, 76105
Research Center
Fort Worth, Texas, 76112
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Fort Worth, Texas, 76133
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Fort Worth, Texas, 76164
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Gallup, New Mexico, 87301
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Grand Prairie, Texas, 75050
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Greenville, North Carolina, 27834
Research Center
Gulfport, Mississippi, 39501
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Houston, Texas, 77054
Research Center
Houston, Texas, 77099
Research Center
Kansas City, Missouri, 64131
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Knoxville, Tennessee, 37923
Research Center
Knoxville, Tennessee, 37924
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La Mesa, California, 91942
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Lauderdale Lakes, Florida, 33313
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Long Beach, California, 90806
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Long Beach, California, 90813
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Los Angeles, California, 90057
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Lubbock, Texas, 79430
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Mansfield, Texas, 76063
Research Center
Meridian, Idaho, 83642
Research Center
Miami, Florida, 33143
Research Center
Miami, Florida, 33173
Research Center
Nashville, Tennessee, 37205
Research Center
Nashville, Tennessee, 37232
Research Center
New Bern, North Carolina, 28562
Research Center
New York, New York, 11355
Research Center
North Brunswick, New Jersey, 08902
Research Center
Northridge, California, 91324
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Ontario, California, 91762
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Orangeburg, South Carolina, 29118
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Pembroke Pines, Florida, 33028
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Phoenix, Arizona, 85012
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Pine Bluff, Arkansas, 71603
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Pontiac, Michigan, 48341
Research Center
Portsmouth, New Hampshire, 03885
Research Center
Raleigh, North Carolina, 27609
Research Center
Rocky Mount, North Carolina, 27804
Research Center
Roseville, California, 95661
Research Center
Saint Ann, Missouri, 63074
Research Center
San Antonio, Texas, 78202
Research Center
San Antonio, Texas, 78221
Research Center
San Diego, California, 92111
Research Center
San Dimas, California, 91773
Research Center
San Gabriel, California, 91776
Research Center
Shorewood, Wisconsin, 53226
Research Center
Shreveport, Louisiana, 71101
Research Center
Springfield, Massachusetts, 01107
Research Center
St Louis, Missouri, 63110
Research Center
Sumter, South Carolina, 29150
Research Center
Tampa, Florida, 33614
Research Center
Tupelo, Mississippi, 38801
Research Center
Whittier, California, 90603

Other trials in United States

Puerto Rico2 sites

Research Center
Caguas, 00725
Research Center
San Juan, 00926

Other trials in Puerto Rico

About this study

Official title: A Phase 3, Open-Label, Randomized, Active-Controlled Study of the Efficacy and Safety of Roxadustat (FG-4592) in the Maintenance Treatment of Anemia in Subjects With End Stage Renal Disease (ESRD) on Stable Dialysis

Read the detailed description

This study will consist of three study periods as follows:

Screening Period of up to 6 weeks (8 weeks if on Mircera)
Treatment Period: a minimum of 52 weeks, a maximum of up to 3 years from the date last participant is randomized. Minimum study duration for participants enrolled under Protocol Amendment 1 or 2 may be less than 52 weeks
A Follow-up period of 4 weeks.

Participants will be randomized in a 1:1 ratio to receive either roxadustat or epoetin alfa (active control) in an open-label manner.

Conditions: CKD Anemia in Stable Dialysis Patients
Being tested: Epoetin Alfa, Roxadustat
Keywords: Anemia, Chronic Kidney Disease, Dialysis, hemodialysis, peritoneal dialysis, hemoglobin, End stage renal disease, Stable Dialysis, erythropoietins, erythropoiesis stimulating agent
Medical subject headings: Anemia, Renal Insufficiency, Chronic, Kidney Failure, Chronic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Epoetin AlfaDrug
Epoetin alfa will be administered per dose and schedule specified in the arm.
RoxadustatDrug
Also called FG-4592
Roxadustat will be administered per dose and schedule specified in the arm.

Study groups in NCT02273726
Study group	Role	What they receive
Roxadustat	Experimental	Participants will receive roxadustat tablets, administered orally 3 times weekly (TIW). Initial roxadustat dose will be based on the participant's average prescribed erythropoietin stimulating agent (ESA) dose in the 4 weeks (if on epoetin or darbepoetin or 8 weeks (if on Mircera®) prior to randomization. Dose adjustments will be permitted to maintain a hemoglobin (Hb) level of approximately 11 grams (g)/deciliter (dL). The maximum roxadustat dose is 3.0 milligrams (mg)/kilogram (kg) per dose or 400 mg per administration (whichever is lower). Receives: Drug: Roxadustat
Epoetin Alfa	Active comparator	Participants on hemodialysis (HD) will receive epoetin alfa, administered intravenously (IV) TIW and participants on home HD or peritoneal dialysis (PD) will receive epoetin alfa, administered subcutaneously (SC). Initial epoetin alfa dose will be based on the participant's average weekly prescribed ESA dose in 4 weeks prior to randomization if on epoetin or darbepoetin, and average monthly (4-week) prescribed ESA dose in 8 weeks prior to randomization if on Mircera®. In case of a change in route of administration from SC to IV (TIW), the initial dose of IV epoetin alfa will be determined by the investigator per local standard of care (SOC). Dose adjustments will follow the recommendations as per the approved country-specific product label (United States Package Insert [USPI] or Summary of Product Characteristics [SmPC]) or local SOC. Receives: Drug: Epoetin Alfa

What is being measured

The primary outcome is the main question the study is designed to answer.

US (FDA) Submission: Mean Hb Change From Baseline to The Average Level During The Evaluation Period (Weeks 28 to 52), Regardless of Rescue Therapy
Hb values under the influence of rescue therapy were not censored in the analysis. Rescue therapy for roxadustat treated participants was defined as recombinant erythropoietin or analogue (ESA) or red blood cell (RBC) transfusion, and rescue therapy for epoetin alfa treated participants was defined as RBC transfusion. Baseline Hb was defined the mean of up to 4 last central lab values prior to the first dose of study treatment. The intermittent missing Hb data was imputed for each treatment relying on non-missing data from all participants within each treatment group using the Monte Carlo Markov Chain (MCMC) imputation model, Monotone missing data were imputed by regression from its own treatment group.
Measured: Baseline (Day 1, Week 0), Weeks 28 to 52
Ex-U.S. Submission: Mean Hb Change From Baseline to the Average Weeks 28 to 36, Without Having Received Rescue Therapy Within 6 Weeks Prior to and During This 8-Week Evaluation Period for Participants Enrolled Under the Original Protocol
Hb values under the influence of rescue therapy were censored up to 6 weeks in the analysis. Rescue therapy for roxadustat treated participants was defined as recombinant erythropoietin or analogue (ESA) or RBC transfusion, and rescue therapy for epoetin alfa treated participants was defined as RBC transfusion. Baseline Hb was defined the mean of up to 4 last central lab values prior to the first dose of study treatment.
Measured: Baseline (Day 1, Week 0), Weeks 28 to 36

Secondary outcomes (9)

US (FDA Submission): Hb Responder Rate- Percentage of Participants With Mean Hb Level ≥10.0 g/dL Averaged Over Weeks 28 to 52, Regardless of Rescue Therapy
Hb values under the influence of rescue therapy were not censored in the analysis. Rescue therapy for roxadustat treated participants was defined as recombinant erythropoietin or analogue (ESA) or RBC transfusion, and rescue therapy for epoetin alfa treated participants was defined as RBC transfusion.
Measured: Weeks 28 to 52
Ex-U.S. Submission: Hb Responder Rate- Percentage of Participants With Mean Hb 10.0 to 12.0 g/dL Averaged Over Weeks 28 to 36, Censoring for Rescue Therapy
Hb values under the influence of a rescue therapy were censored up to 6 weeks in the analysis. Rescue therapy for roxadustat treated participants was defined as recombinant erythropoietin or analogue (ESA) or RBC transfusion, and rescue therapy for epoetin alfa treated participants was defined as RBC transfusion.
Measured: Weeks 28 to 36
Change From Baseline in Low-Density Lipoprotein (LDL) Cholesterol Averaged Over Weeks 12 to 28
Baseline LDL Cholesterol was defined as the last available value prior to the first dose of study treatment.
Measured: Baseline (Day 1, Week 0), Weeks 12 to 28
Change From Baseline in Hb Levels Averaged Over Weeks 18 to 24 Regardless of Rescue Therapy in Participants Whose Baseline High Sensitivity C-Reactive Protein (Hs-CRP)> Upper Limit of Normal (ULN)
Hb values under the influence of rescue therapy were not censored in the analysis. Rescue therapy for roxadustat treated participants was defined as recombinant erythropoietin or analogue (ESA) or RBC transfusion, and rescue therapy for epoetin alfa treated participants was defined as RBC transfusion. Baseline Hb was defined the mean of up to 4 last central lab values prior to the first dose of study treatment. The intermittent missing Hb data was imputed for each treatment relying on non-missing data from all participants within each treatment group using the MCMC imputation model, Monotone missing data were imputed by regression from its own treatment group.
Measured: Baseline (Day 1, Week 0), Weeks 18 to 24
Average Monthly IV Iron Use Per Patient-Exposure-Month (PEM) During Weeks 28 to 52
Monthly iron use for each participant= Total IV iron in mg / [(last dose date - first dose date of study medication in the period)+1]/ 28.
Measured: Weeks 28 to 52
Time to First RBC Transfusion
Median time to event (weeks) was calculated using Kaplan Meier Survival Estimates.
Measured: Baseline (Day 1, Week 0) up to last dose of study drug (maximum treatment duration was 183.7 weeks for roxadustat and 180.4 weeks for epoetin alfa)
Change From Baseline in Mean Arterial Pressure (MAP) Averaged Over Weeks 20 to 28
Baseline MAP was defined as the mean of values obtained within 6 weeks prior to the first dose of study treatment.
Measured: Baseline (Day 1, Week 0), Weeks 20 to 28
Time to First Exacerbation of Hypertension During Weeks 28 to 52
An exacerbation of hypertension was defined as increase from baseline of ≥20 mmHg in systolic blood pressure (sBP) and sBP ≥170 mmHg or an increase from baseline of ≥15 mmHg in diastolic blood pressure (dBP) and dBP ≥100 mmHg. Median time to event (weeks) was calculated using Kaplan Meier Survival Estimates.
Measured: Weeks 28 to 52
Change From Baseline in Short Form 36 (SF-36) Version 2 Physical Functioning Subscore and Vitality Subscore at Weeks 12 to 28
The SF-36 V2 consists of 36 questions covering 8 health domains: physical functioning (10 items), bodily pain (2 items), role limitations due to physical problems (4 items), role limitations due to emotional problems (3 items), general health perceptions (5 items), mental health (5 items), social function (2 items), and vitality (4 items). The physical functioning subscore and vitality subscore are reported. Each scale was transformed into 0-100 score, with higher scores indicating better health status. Baseline score was defined as the last physical functioning value or vitality value, as applicable, prior to the first dose of study drug.
Measured: Baseline (Day 1, Week 0), Weeks 12 to 28

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

15 Jan 201519 Sep 2018

First posted24 Oct 2014 (estimated)
Study start15 Jan 2015
Primary completion19 Sep 2018
Study completion19 Sep 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for CKD Anemia in Stable Dialysis PatientsStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 741 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02273726
Sponsor's protocol ID: FGCL-4592-064
Status last verified: Sep 2021
First submitted: 22 Oct 2014
Last updated: 29 Oct 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

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.
PubMed 38363466
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.
PubMed 36749544
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.
PubMed 36005278

Study at a glance

From the registry record, last updated by the sponsor on 29 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 3, Open-Label, Randomized, Active-Controlled Study of the Efficacy and Safety of Roxadustat (FG-4592) in the Maintenance Treatment of Anemia in Subjects With End Stage Renal Disease (ESRD) on Stable Dialysis
ClinicalTrials.gov ID: NCT02273726
Acronym / sponsor ID: FGCL-4592-064
Conditions: CKD Anemia in Stable Dialysis Patients
Keywords: Anemia, Chronic Kidney Disease, Dialysis, hemodialysis, peritoneal dialysis, hemoglobin, End stage renal disease, Stable Dialysis
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 741 participants (actual)
Lead sponsor: Kyntra BioIndustry (pharma, biotech, devices)
Collaborators: Astellas Pharma Europe B.V., AstraZeneca
Study start: 15 Jan 2015 (actual)
Primary completion: 19 Sep 2018 (actual)
Study completion: 19 Sep 2018 (actual)
First posted: 24 Oct 2014 (estimated)
Results: Posted 29 Oct 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

This study will consist of three study periods as follows:

Screening Period of up to 6 weeks (8 weeks if on Mircera)
Treatment Period: a minimum of 52 weeks, a maximum of up to 3 years from the date last participant is randomized. Minimum study duration for participants enrolled under Protocol Amendment 1 or 2 may be less than 52 weeks
A Follow-up period of 4 weeks.

Participants will be randomized in a 1:1 ratio to receive either roxadustat or epoetin alfa (active control) in an open-label manner.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Roxadustat	Experimental	Drug: RoxadustatParticipants will receive roxadustat tablets, administered orally 3 times weekly (TIW). Initial roxadustat dose will be based on the participant's average prescribed erythropoietin stimulating agent (ESA) dose in the 4 weeks (if on epoetin or darbepoetin or 8 weeks (if on Mircera®) prior to randomization. Dose adjustments will be permitted to maintain a hemoglobin (Hb) level of approximately 11 grams (g)/deciliter (dL). The maximum roxadustat dose is 3.0 milligrams (mg)/kilogram (kg) per dose or 400 mg per administration (whichever is lower).
Epoetin Alfa	Active comparator	Drug: Epoetin AlfaParticipants on hemodialysis (HD) will receive epoetin alfa, administered intravenously (IV) TIW and participants on home HD or peritoneal dialysis (PD) will receive epoetin alfa, administered subcutaneously (SC). Initial epoetin alfa dose will be based on the participant's average weekly prescribed ESA dose in 4 weeks prior to randomization if on epoetin or darbepoetin, and average monthly (4-week) prescribed ESA dose in 8 weeks prior to randomization if on Mircera®. In case of a change in route of administration from SC to IV (TIW), the initial dose of IV epoetin alfa will be determined by the investigator per local standard of care (SOC). Dose adjustments will follow the recommendations as per the approved country-specific product label (United States Package Insert [USPI] or Summary of Product Characteristics [SmPC]) or local SOC.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

Receiving dialysis for ESRD for ≥3 months. Incident dialysis participants (under Amendment 1 and 2) receiving dialysis for ESRD for ≥ 2 weeks but ≤ 4 months at the time of randomization
Participants must be on ESA for ≥ 8 weeks prior to screening; incident dialysis participants must be on ESA for ≥ 4 weeks prior to screening.
Mean of the 3 most recent central lab Hb values during the Screening Period must be ≥ 9.0 g/dL and ≤ 12.0 g/dL (for incident dialysis participants, mean of the 2 most recent Hb values must be ≥ 8.5 g/dL and ≤ 12.0 g/dL); with an absolute difference of ≤ 1.3 g/dL between the highest and the lowest value. Samples are obtained at least 4 days apart (2 days under Amendment 2) and the last Hb value must be within 10 days prior to the randomization visit
Participants with ferritin level ≥ 100 nanograms (ng)/milliliter (mL) (<100 ng/mL under Amendment 2) or transferrin saturation (TSAT) ≥ 20% (<20% under Amendment 2) at screening may qualify upon receiving iron supplement (per local standard of care)
Participants with a serum folate and Vitamin B12 ≥ lower limit of normal (LLN) (< LLN under Amendment 2) at screening may qualify upon receiving supplement (per local standard of care)

Key exclusion criteria (15 listed)

Participant has received an red blood cell (RBC) transfusion within 8 weeks (4 weeks under Amendment 2) prior to randomization
Participant has known history of myelodysplastic syndrome or multiple myeloma
Participant has known inherited disease such as thalassemia or sickle cell anemia or other known causes for anemia other than chronic kidney disease.
Participant has known hemosiderosis, hemochromatosis, coagulation disorder,or hypercoagulable condition
Participant has known chronic inflammatory disease that could cause anemia

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Epoetin AlfaEpoetin alfa will be administered per dose and schedule specified in the arm.	Drug	Epoetin Alfa
RoxadustatAlso: FG-4592Roxadustat will be administered per dose and schedule specified in the arm.	Drug	Roxadustat

Primary outcome

US (FDA) Submission: Mean Hb Change From Baseline to The Average Level During The Evaluation Period (Weeks 28 to 52), Regardless of Rescue Therapy
Time frame: Baseline (Day 1, Week 0), Weeks 28 to 52
Hb values under the influence of rescue therapy were not censored in the analysis. Rescue therapy for roxadustat treated participants was defined as recombinant erythropoietin or analogue (ESA) or red blood cell (RBC) transfusion, and rescue therapy for epoetin alfa treated participants was defined as RBC transfusion. Baseline Hb was defined the mean of up to 4 last central lab values prior to the first dose of study treatment. The intermittent missing Hb data was imputed for each treatment relying on non-missing data from all participants within each treatment group using the Monte Carlo Markov Chain (MCMC) imputation model, Monotone missing data were imputed by regression from its own treatment group.
Ex-U.S. Submission: Mean Hb Change From Baseline to the Average Weeks 28 to 36, Without Having Received Rescue Therapy Within 6 Weeks Prior to and During This 8-Week Evaluation Period for Participants Enrolled Under the Original Protocol
Time frame: Baseline (Day 1, Week 0), Weeks 28 to 36
Hb values under the influence of rescue therapy were censored up to 6 weeks in the analysis. Rescue therapy for roxadustat treated participants was defined as recombinant erythropoietin or analogue (ESA) or RBC transfusion, and rescue therapy for epoetin alfa treated participants was defined as RBC transfusion. Baseline Hb was defined the mean of up to 4 last central lab values prior to the first dose of study treatment.

9 secondary outcomes

US (FDA Submission): Hb Responder Rate- Percentage of Participants With Mean Hb Level ≥10.0 g/dL Averaged Over Weeks 28 to 52, Regardless of Rescue Therapy
Time frame: Weeks 28 to 52
Ex-U.S. Submission: Hb Responder Rate- Percentage of Participants With Mean Hb 10.0 to 12.0 g/dL Averaged Over Weeks 28 to 36, Censoring for Rescue Therapy
Time frame: Weeks 28 to 36
Change From Baseline in Low-Density Lipoprotein (LDL) Cholesterol Averaged Over Weeks 12 to 28
Time frame: Baseline (Day 1, Week 0), Weeks 12 to 28
Change From Baseline in Hb Levels Averaged Over Weeks 18 to 24 Regardless of Rescue Therapy in Participants Whose Baseline High Sensitivity C-Reactive Protein (Hs-CRP)> Upper Limit of Normal (ULN)
Time frame: Baseline (Day 1, Week 0), Weeks 18 to 24
Average Monthly IV Iron Use Per Patient-Exposure-Month (PEM) During Weeks 28 to 52
Time frame: Weeks 28 to 52
Time to First RBC Transfusion
Time frame: Baseline (Day 1, Week 0) up to last dose of study drug (maximum treatment duration was 183.7 weeks for roxadustat and 180.4 weeks for epoetin alfa)
Change From Baseline in Mean Arterial Pressure (MAP) Averaged Over Weeks 20 to 28
Time frame: Baseline (Day 1, Week 0), Weeks 20 to 28
Time to First Exacerbation of Hypertension During Weeks 28 to 52
Time frame: Weeks 28 to 52
Change From Baseline in Short Form 36 (SF-36) Version 2 Physical Functioning Subscore and Vitality Subscore at Weeks 12 to 28
Time frame: Baseline (Day 1, Week 0), Weeks 12 to 28

Results and safety

Results posted to the registry on 29 Oct 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Roxadustat	370	127
Epoetin Alfa	371	183

Primary outcome: US (FDA) Submission: Mean Hb Change From Baseline to The Average Level During The Evaluation Period (Weeks 28 to 52), Regardless of Rescue Therapy

Time frame: Baseline (Day 1, Week 0), Weeks 28 to 52. Mean (Standard Deviation). Unit: g/dL

Measure	Roxadustat n = 370	Epoetin Alfa n = 371
Baseline	10.30 (0.661)	10.31 (0.656)
Change at Weeks 28 to 52	0.39 (0.934)	-0.09 (0.838)

Roxadustat vs Epoetin Alfa: LS Mean Difference: 0.48 (95% CI 0.365 to 0.591), p <0.0001, ANCOVA

Population analysed: ITT Population included all randomized participants.

Primary outcome: Ex-U.S. Submission: Mean Hb Change From Baseline to the Average Weeks 28 to 36, Without Having Received Rescue Therapy Within 6 Weeks Prior to and During This 8-Week Evaluation Period for Participants Enrolled Under the Original Protocol

Time frame: Baseline (Day 1, Week 0), Weeks 28 to 36. Mean (Standard Deviation). Unit: g/dL

Measure	Roxadustat n = 303	Epoetin Alfa n = 324
Baseline	10.33 (0.639)	10.35 (0.614)
Change at Weeks 28 to 36	0.54 (1.022)	-0.03 (0.897)

Roxadustat vs Epoetin Alfa: LS Mean Difference: 0.55 (95% CI 0.404 to 0.687), p <0.0001, Mixed Models Analysis

Population analysed: Per protocol set (PPS) population included all participants in full analysis set (FAS) population (all randomized participants who received at least 1 dose of study drug and had at least 1 postdose Hb assessment) who received at least 8 weeks of treatment and were without major protocol violations. 'Overall number of participants analyzed'=participants evaluable for this outcome measure. 'Number analyzed'=participants evaluable at specified timepoint.

9 secondary outcomes are reported in the full results.

Adverse events

Time frame: Baseline (Day 1, Week 0) up to 28 days after the last dose of study drug (maximum treatment duration was 183.7 weeks for roxadustat and 180.4 weeks for epoetin alfa). Mortality presented is for the timeframe of Baseline (Day 1, Week 0) up to end of treatment (maximum treatment duration was 183.7 weeks for roxadustat and 180.4 weeks for epoetin alfa).. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Roxadustat	242 of 370 (65.4%)	286 of 370 (77.3%)	70 of 370
Epoetin Alfa	248 of 370 (67%)	292 of 370 (78.9%)	62 of 370

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 29 Oct 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 38363466Hamano 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.
Derived from this study: PubMed 36749544Barratt 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.
Derived from this study: PubMed 36005278Natale 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.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Meraf Eyassu study director

Kyntra Bio

76 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Epoetin Alfa and Roxadustat in people with CKD Anemia in Stable Dialysis Patients, run by Kyntra Bio at 76 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 76 sites in United States, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Oct 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

US (FDA) Submission: Mean Hb Change From Baseline to The Average Level During The Evaluation Period (Weeks 28 to 52), Regardless of Rescue Therapy (time frame: Baseline (Day 1, Week 0), Weeks 28 to 52). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02273726, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Oct 2021.