Trial Outcomes & Findings for Safety and Efficacy Study of Roxadustat to Treat Anemia in Patients With Chronic Kidney Disease, on Dialysis. (NCT NCT02174731)

Last Updated: 2019-12-16

Results Overview

Baseline Hb was defined as the mean of the three last central laboratory Hb values from the screening and randomization visits. Mean change in Hb from baseline to the participants mean level from Week 28 to Week 52 was analyzed using a missing at random (MAR) based multiple imputation Analysis of Covariance (ANCOVA). Baseline Hb was used as a covariate and treatment group, cardiovascular (CV) history, geographic region and dialysis duration as fixed effects. The adjusted least squares (LS) mean estimates of change from baseline during Week 28 to Week 52 are presented.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

2133 participants

Primary outcome timeframe

Baseline (Day 1, Week 0), Week 28 to 52

Results posted on

2019-12-16

Participant Flow

This study was conducted at 197 centers in 18 countries worldwide across the United States (US), Canada, Latin America, Australia, Asia and Europe between 01 July 2014 and 26 September 2018. Participants with chronic kidney disease (CKD) who were on dialysis were recruited in this study.

Study had a screening period (up to 6 weeks), treatment period (up to 4 years) and follow-up period (4 weeks after treatment period for those who completed treatment). 2133 participants were randomized, of which 2106 were included in the analysis and 27 were excluded. Only participants included in the analysis are presented in the participant flow.

Participant milestones

Participant milestones
Measure	Roxadustat Participants received roxadustat tablets orally three times a week (TIW) throughout the treatment period (up to 4 years). For hemodialysis (HD) participants, it was recommended that roxadustat was taken after completion of the HD session. For participants treated with an erythropoietin analogue at study entry, selection of initial roxadustat dose was based on the participant's erythropoietin analogue dose at screening Visit 1. Participants not treated with an erythropoietin analogue at study entry initiated roxadustat using a tiered, weight-based dosing scheme. Doses were titrated to achieve and maintain hemoglobin (Hb) values of 11±1 grams per deciliter (g/dL). Dose adjustments were permitted starting at Week 4 and at intervals of every 4 weeks using a dose adjustment algorithm.	Epoetin Alfa Participants received epoetin alfa (only use of Procrit®, Eprex® and Epogen® permitted in the study) subcutaneous (SC) or intravenous (IV) injection TIW, except for participants treated with epoetin alfa in a less frequent regimen prior to study entry. For participants treated with an erythropoietin analogue at study entry, the initial dose of epoetin alfa was the actual dose administered at screening Visit 1. Participants treated with darbepoetin alfa or methoxy polyethylene glycol-epoetin beta prior to study entry initially received epoetin alfa at doses based on a conversion factor. For participants not treated with an erythropoietin analogue at study entry, the initial dose of epoetin alfa was 50 international unit per kilogram (IU/kg) TIW. Dose adjustments were to be consistent with local approved prescribing information.
Overall Study STARTED	1051	1055
Overall Study Received Treatment	1048	1053
Overall Study COMPLETED	982	990
Overall Study NOT COMPLETED	69	65

Reasons for withdrawal

Reasons for withdrawal
Measure	Roxadustat Participants received roxadustat tablets orally three times a week (TIW) throughout the treatment period (up to 4 years). For hemodialysis (HD) participants, it was recommended that roxadustat was taken after completion of the HD session. For participants treated with an erythropoietin analogue at study entry, selection of initial roxadustat dose was based on the participant's erythropoietin analogue dose at screening Visit 1. Participants not treated with an erythropoietin analogue at study entry initiated roxadustat using a tiered, weight-based dosing scheme. Doses were titrated to achieve and maintain hemoglobin (Hb) values of 11±1 grams per deciliter (g/dL). Dose adjustments were permitted starting at Week 4 and at intervals of every 4 weeks using a dose adjustment algorithm.	Epoetin Alfa Participants received epoetin alfa (only use of Procrit®, Eprex® and Epogen® permitted in the study) subcutaneous (SC) or intravenous (IV) injection TIW, except for participants treated with epoetin alfa in a less frequent regimen prior to study entry. For participants treated with an erythropoietin analogue at study entry, the initial dose of epoetin alfa was the actual dose administered at screening Visit 1. Participants treated with darbepoetin alfa or methoxy polyethylene glycol-epoetin beta prior to study entry initially received epoetin alfa at doses based on a conversion factor. For participants not treated with an erythropoietin analogue at study entry, the initial dose of epoetin alfa was 50 international unit per kilogram (IU/kg) TIW. Dose adjustments were to be consistent with local approved prescribing information.
Overall Study Participant decision	67	64
Overall Study Incorrect enrolment before randomization	0	1
Overall Study Missing	2	0

Baseline Characteristics

Safety and Efficacy Study of Roxadustat to Treat Anemia in Patients With Chronic Kidney Disease, on Dialysis.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Roxadustat n=1051 Participants Participants received roxadustat tablets orally TIW throughout the treatment period (up to 4 years). For HD participants, it was recommended that roxadustat was taken after completion of the HD session. For participants treated with an erythropoietin analogue at study entry, selection of initial roxadustat dose was based on the participant's erythropoietin analogue dose at screening Visit 1. Participants not treated with an erythropoietin analogue at study entry initiated roxadustat using a tiered, weight-based dosing scheme. Doses were titrated to achieve and maintain Hb values of 11±1 g/dL. Dose adjustments were permitted starting at Week 4 and at intervals of every 4 weeks using a dose adjustment algorithm.	Epoetin Alfa n=1055 Participants Participants received epoetin alfa (only use of Procrit®, Eprex® and Epogen® permitted in the study) SC or IV injection TIW, except for participants treated with epoetin alfa in a less frequent regimen prior to study entry. For participants treated with an erythropoietin analogue at study entry, the initial dose of epoetin alfa was the actual dose administered at screening Visit 1. Participants treated with darbepoetin alfa or methoxy polyethylene glycol-epoetin beta prior to study entry initially received epoetin alfa at doses based on a conversion factor. For participants not treated with an erythropoietin analogue at study entry, the initial dose of epoetin alfa was 50 IU/kg TIW. Dose adjustments were to be consistent with local approved prescribing information.	Total n=2106 Participants Total of all reporting groups
Age, Continuous	53.5 years STANDARD_DEVIATION 15.30 • n=5 Participants	54.5 years STANDARD_DEVIATION 14.97 • n=7 Participants	54.0 years STANDARD_DEVIATION 15.14 • n=5 Participants
Sex: Female, Male Female	426 Participants n=5 Participants	429 Participants n=7 Participants	855 Participants n=5 Participants
Sex: Female, Male Male	625 Participants n=5 Participants	626 Participants n=7 Participants	1251 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	268 Participants n=5 Participants	271 Participants n=7 Participants	539 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	783 Participants n=5 Participants	784 Participants n=7 Participants	1567 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized White	597 Participants n=5 Participants	598 Participants n=7 Participants	1195 Participants n=5 Participants
Race/Ethnicity, Customized Black of African American	148 Participants n=5 Participants	158 Participants n=7 Participants	306 Participants n=5 Participants
Race/Ethnicity, Customized Asian	208 Participants n=5 Participants	198 Participants n=7 Participants	406 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	5 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	50 Participants n=5 Participants	62 Participants n=7 Participants	112 Participants n=5 Participants
Race/Ethnicity, Customized Other	43 Participants n=5 Participants	36 Participants n=7 Participants	79 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1, Week 0), Week 28 to 52

Outcome measures

Outcome measures
Measure	Roxadustat n=1003 Participants Participants received roxadustat tablets orally TIW throughout the treatment period (up to 4 years). For HD participants, it was recommended that roxadustat was taken after completion of the HD session. For participants treated with an erythropoietin analogue at study entry, selection of initial roxadustat dose was based on the participant's erythropoietin analogue dose at screening Visit 1. Participants not treated with an erythropoietin analogue at study entry initiated roxadustat using a tiered, weight-based dosing scheme. Doses were titrated to achieve and maintain Hb values of 11±1 g/dL. Dose adjustments were permitted starting at Week 4 and at intervals of every 4 weeks using a dose adjustment algorithm.	Epoetin Alfa n=1016 Participants Participants received epoetin alfa (only use of Procrit®, Eprex® and Epogen® permitted in the study) SC or IV injection TIW, except for participants treated with epoetin alfa in a less frequent regimen prior to study entry. For participants treated with an erythropoietin analogue at study entry, the initial dose of epoetin alfa was the actual dose administered at screening Visit 1. Participants treated with darbepoetin alfa or methoxy polyethylene glycol-epoetin beta prior to study entry initially received epoetin alfa at doses based on a conversion factor. For participants not treated with an erythropoietin analogue at study entry, the initial dose of epoetin alfa was 50 IU/kg TIW. Dose adjustments were to be consistent with local approved prescribing information.
Mean Change From Baseline in Hb Averaged Over Week 28 to Week 52	0.77 g/dL Standard Error 0.041	0.68 g/dL Standard Error 0.040

SECONDARY outcome

Timeframe: Baseline (Day 1, Week 0), Week 28 to 36

Population: The Per Protocol Set (PPS) included all randomized participants without important protocol deviations who had received at least 8 weeks of study treatment and had valid corresponding Hb measurements. Participants from the PPS, with data available for analysis are presented.

Baseline Hb was defined as the mean of the three last central laboratory Hb values from the screening and randomization visits. Mean change in Hb from baseline to the participants mean level from Week 28 to Week 36,without having received rescue therapy within 6 weeks prior to and during this 8 week evaluation period was analysed using Mixed Model of Repeated Measures (MMRM). Baseline Hb was used as a covariate and treatment group, CV history, geographic region and dialysis duration as fixed effects. The adjusted LS mean estimates of change from baseline during Week 28 to Week 36 are presented for participants that did not receive rescue therapy within 6 weeks prior to and during this 8-week evaluation period.

Outcome measures

Outcome measures
Measure	Roxadustat n=836 Participants Participants received roxadustat tablets orally TIW throughout the treatment period (up to 4 years). For HD participants, it was recommended that roxadustat was taken after completion of the HD session. For participants treated with an erythropoietin analogue at study entry, selection of initial roxadustat dose was based on the participant's erythropoietin analogue dose at screening Visit 1. Participants not treated with an erythropoietin analogue at study entry initiated roxadustat using a tiered, weight-based dosing scheme. Doses were titrated to achieve and maintain Hb values of 11±1 g/dL. Dose adjustments were permitted starting at Week 4 and at intervals of every 4 weeks using a dose adjustment algorithm.	Epoetin Alfa n=864 Participants Participants received epoetin alfa (only use of Procrit®, Eprex® and Epogen® permitted in the study) SC or IV injection TIW, except for participants treated with epoetin alfa in a less frequent regimen prior to study entry. For participants treated with an erythropoietin analogue at study entry, the initial dose of epoetin alfa was the actual dose administered at screening Visit 1. Participants treated with darbepoetin alfa or methoxy polyethylene glycol-epoetin beta prior to study entry initially received epoetin alfa at doses based on a conversion factor. For participants not treated with an erythropoietin analogue at study entry, the initial dose of epoetin alfa was 50 IU/kg TIW. Dose adjustments were to be consistent with local approved prescribing information.
Change in Hb From Baseline to the Mean Level During the Evaluation Period (Week 28 to Week 36) Without Having Received Rescue Therapy Within 6 Weeks Prior to and During the 8-Week Evaluation Period	0.88 g/dL Standard Error 0.044	0.74 g/dL Standard Error 0.043

SECONDARY outcome

Timeframe: Week 28 to 52

Population: The ITT analysis set included all participants who were randomized to IP irrespective of their protocol adherence and continued participation in the study, except for those excluded from analysis. Participants without any Hb measurements from Week 28 were not included in the analysis.

The proportion of total time was computed as follows: For each participant, the recorded Hb values were first linearly interpolated between measurements. The time this interpolated curve was \>=10 g/dL was computed and subsequently divided by the time between the measurements from Week 28 to Week 52. The difference between roxadustat and epoetin alfa were compared using ANCOVA. Baseline Hb was used as a covariate and the treatment groups, CV history, geographic region and dialysis duration as fixed effects.

Outcome measures

Outcome measures
Measure	Roxadustat n=896 Participants Participants received roxadustat tablets orally TIW throughout the treatment period (up to 4 years). For HD participants, it was recommended that roxadustat was taken after completion of the HD session. For participants treated with an erythropoietin analogue at study entry, selection of initial roxadustat dose was based on the participant's erythropoietin analogue dose at screening Visit 1. Participants not treated with an erythropoietin analogue at study entry initiated roxadustat using a tiered, weight-based dosing scheme. Doses were titrated to achieve and maintain Hb values of 11±1 g/dL. Dose adjustments were permitted starting at Week 4 and at intervals of every 4 weeks using a dose adjustment algorithm.	Epoetin Alfa n=941 Participants Participants received epoetin alfa (only use of Procrit®, Eprex® and Epogen® permitted in the study) SC or IV injection TIW, except for participants treated with epoetin alfa in a less frequent regimen prior to study entry. For participants treated with an erythropoietin analogue at study entry, the initial dose of epoetin alfa was the actual dose administered at screening Visit 1. Participants treated with darbepoetin alfa or methoxy polyethylene glycol-epoetin beta prior to study entry initially received epoetin alfa at doses based on a conversion factor. For participants not treated with an erythropoietin analogue at study entry, the initial dose of epoetin alfa was 50 IU/kg TIW. Dose adjustments were to be consistent with local approved prescribing information.
Proportion of Total Time of Hb Within the Interval of >=10 g/dL From Week 28 to Week 52	0.79 proportion of total time Standard Error 0.012	0.76 proportion of total time Standard Error 0.012

SECONDARY outcome

Timeframe: Week 28 to 52

The proportion of total time was computed as follows: For each participant, the recorded Hb values were first linearly interpolated between measurements. The time this interpolated curve was within 10-12 g/dL was computed and subsequently divided by the time between the measurement from Week 28 to 52. The difference between roxadustat and epoetin alfa were compared using ANCOVA. Baseline Hb was used as a covariate and the treatment groups, CV history, geographic region and dialysis duration as fixed effects.

Outcome measures

Outcome measures
Measure	Roxadustat n=896 Participants Participants received roxadustat tablets orally TIW throughout the treatment period (up to 4 years). For HD participants, it was recommended that roxadustat was taken after completion of the HD session. For participants treated with an erythropoietin analogue at study entry, selection of initial roxadustat dose was based on the participant's erythropoietin analogue dose at screening Visit 1. Participants not treated with an erythropoietin analogue at study entry initiated roxadustat using a tiered, weight-based dosing scheme. Doses were titrated to achieve and maintain Hb values of 11±1 g/dL. Dose adjustments were permitted starting at Week 4 and at intervals of every 4 weeks using a dose adjustment algorithm.	Epoetin Alfa n=941 Participants Participants received epoetin alfa (only use of Procrit®, Eprex® and Epogen® permitted in the study) SC or IV injection TIW, except for participants treated with epoetin alfa in a less frequent regimen prior to study entry. For participants treated with an erythropoietin analogue at study entry, the initial dose of epoetin alfa was the actual dose administered at screening Visit 1. Participants treated with darbepoetin alfa or methoxy polyethylene glycol-epoetin beta prior to study entry initially received epoetin alfa at doses based on a conversion factor. For participants not treated with an erythropoietin analogue at study entry, the initial dose of epoetin alfa was 50 IU/kg TIW. Dose adjustments were to be consistent with local approved prescribing information.
Proportion of Total Time of Hb Within the Interval of 10 to 12 g/dL From Week 28 to Week 52	0.65 proportion of total time Standard Error 0.013	0.63 proportion of total time Standard Error 0.012

SECONDARY outcome

Timeframe: Baseline (Day 1, Week 0) to Week 24

Baseline LDL was defined as the last result obtained prior to randomization. Mean changes in LDL cholesterol from baseline to Week 24 was analysed using ANCOVA. Baseline Hb and baseline LDL were used as covariates and treatment groups, CV history, geographic region and dialysis duration as fixed effects. The adjusted LS mean estimates of change from baseline to Week 24 are presented.

Outcome measures

Outcome measures
Measure	Roxadustat n=902 Participants Participants received roxadustat tablets orally TIW throughout the treatment period (up to 4 years). For HD participants, it was recommended that roxadustat was taken after completion of the HD session. For participants treated with an erythropoietin analogue at study entry, selection of initial roxadustat dose was based on the participant's erythropoietin analogue dose at screening Visit 1. Participants not treated with an erythropoietin analogue at study entry initiated roxadustat using a tiered, weight-based dosing scheme. Doses were titrated to achieve and maintain Hb values of 11±1 g/dL. Dose adjustments were permitted starting at Week 4 and at intervals of every 4 weeks using a dose adjustment algorithm.	Epoetin Alfa n=937 Participants Participants received epoetin alfa (only use of Procrit®, Eprex® and Epogen® permitted in the study) SC or IV injection TIW, except for participants treated with epoetin alfa in a less frequent regimen prior to study entry. For participants treated with an erythropoietin analogue at study entry, the initial dose of epoetin alfa was the actual dose administered at screening Visit 1. Participants treated with darbepoetin alfa or methoxy polyethylene glycol-epoetin beta prior to study entry initially received epoetin alfa at doses based on a conversion factor. For participants not treated with an erythropoietin analogue at study entry, the initial dose of epoetin alfa was 50 IU/kg TIW. Dose adjustments were to be consistent with local approved prescribing information.
Mean Change in Low-Density Lipoprotein (LDL) Cholesterol From Baseline to Week 24	-0.38 millimole per liter Standard Error 0.026	-0.05 millimole per liter Standard Error 0.026

SECONDARY outcome

Timeframe: Baseline (Day 1, Week 0), Week 28 to 52

Population: The ITT analysis set included all participants who were randomized to IP irrespective of their protocol adherence and continued participation in the study, except for those excluded from analysis. Only participants who consented to the use of donated biomarker samples and had baseline hsCRP \>ULN were included in the analysis.

Baseline hsCRP was quantified from stored biomarker samples obtained at randomization. Baseline Hb is defined as the mean of the three last central laboratory Hb values from the screening and randomization visits. Changes in Hb from baseline to mean value during Weeks 28 to 52 in participants with baseline hsCRP \>ULN was analyzed using a MAR based multiple imputation ANCOVA. Baseline Hb was used as a covariate and treatment group, CV history, geographic region and dialysis duration as fixed effects. The adjusted LS mean estimates of change from baseline during Week 28 to Week 52 are presented.

Outcome measures

Outcome measures
Measure	Roxadustat n=280 Participants Participants received roxadustat tablets orally TIW throughout the treatment period (up to 4 years). For HD participants, it was recommended that roxadustat was taken after completion of the HD session. For participants treated with an erythropoietin analogue at study entry, selection of initial roxadustat dose was based on the participant's erythropoietin analogue dose at screening Visit 1. Participants not treated with an erythropoietin analogue at study entry initiated roxadustat using a tiered, weight-based dosing scheme. Doses were titrated to achieve and maintain Hb values of 11±1 g/dL. Dose adjustments were permitted starting at Week 4 and at intervals of every 4 weeks using a dose adjustment algorithm.	Epoetin Alfa n=301 Participants Participants received epoetin alfa (only use of Procrit®, Eprex® and Epogen® permitted in the study) SC or IV injection TIW, except for participants treated with epoetin alfa in a less frequent regimen prior to study entry. For participants treated with an erythropoietin analogue at study entry, the initial dose of epoetin alfa was the actual dose administered at screening Visit 1. Participants treated with darbepoetin alfa or methoxy polyethylene glycol-epoetin beta prior to study entry initially received epoetin alfa at doses based on a conversion factor. For participants not treated with an erythropoietin analogue at study entry, the initial dose of epoetin alfa was 50 IU/kg TIW. Dose adjustments were to be consistent with local approved prescribing information.
Mean Change in Hb From Baseline to the Participant's Mean Level Between Week 28 to Week 52 in Participants With Baseline High-Sensitivity C-Reactive Protein (hsCRP) Greater Than the Upper Limit of Normal (ULN)	0.80 g/dL Standard Error 0.077	0.59 g/dL Standard Error 0.076

SECONDARY outcome

Timeframe: Week 36 to EOS (4 weeks after the treatment period)

Oral iron supplementation was allowed for both treatment groups without restriction. Oral iron was recommended for dietary supplementation to support erythropoiesis and as the first line treatment for prevention and treatment of iron deficiency, unless the participant was intolerant to this route of treatment. In participants receiving roxadustat, the Investigator was allowed to initiate the use of an approved IV iron supplement if a participant's Hb value had not sufficiently responded to 2 or more dose increases of the IP, and ferritin \<100 nanogram per milliliter (ng/mL) or transferrin saturation (TSAT) \<20%. IP treatment was allowed to continue during IV iron administration. Discontinuation of IV iron supplementation was recommended once the participant was no longer considered to be iron deficient (ferritin \>100 ng/mL and TSAT \>20%).

Outcome measures

Outcome measures
Measure	Roxadustat n=885 Participants Participants received roxadustat tablets orally TIW throughout the treatment period (up to 4 years). For HD participants, it was recommended that roxadustat was taken after completion of the HD session. For participants treated with an erythropoietin analogue at study entry, selection of initial roxadustat dose was based on the participant's erythropoietin analogue dose at screening Visit 1. Participants not treated with an erythropoietin analogue at study entry initiated roxadustat using a tiered, weight-based dosing scheme. Doses were titrated to achieve and maintain Hb values of 11±1 g/dL. Dose adjustments were permitted starting at Week 4 and at intervals of every 4 weeks using a dose adjustment algorithm.	Epoetin Alfa n=920 Participants Participants received epoetin alfa (only use of Procrit®, Eprex® and Epogen® permitted in the study) SC or IV injection TIW, except for participants treated with epoetin alfa in a less frequent regimen prior to study entry. For participants treated with an erythropoietin analogue at study entry, the initial dose of epoetin alfa was the actual dose administered at screening Visit 1. Participants treated with darbepoetin alfa or methoxy polyethylene glycol-epoetin beta prior to study entry initially received epoetin alfa at doses based on a conversion factor. For participants not treated with an erythropoietin analogue at study entry, the initial dose of epoetin alfa was 50 IU/kg TIW. Dose adjustments were to be consistent with local approved prescribing information.
Mean Monthly IV Iron Use From Week 36 to End of Study (EOS)	58.71 milligram per month Standard Deviation 236.12	91.37 milligram per month Standard Deviation 225.64

SECONDARY outcome

Timeframe: Baseline (Day 1, Week 0) up to EOS (4 weeks after the treatment period)

Population: The on-treatment+3 days safety analysis set included all participants who received at least 1 dose of randomized IP, except for those excluded from analysis. Participants were censored at 3 days after the last administration of the IP.

Time-to-first RBC transfusion as rescue therapy was calculated as (date of first occurrence of any RBC transfusion as rescue therapy, or date of censoring if no event had occurred) - (date of first dose of IP) + 1. Event rate was calculated as (number of participants with event) divided by (the total number of days at risk for event across all participants in given group divided by 365.25) multiplied by 100. The event rate is presented for participants with events.

Outcome measures

Outcome measures
Measure	Roxadustat n=1048 Participants Participants received roxadustat tablets orally TIW throughout the treatment period (up to 4 years). For HD participants, it was recommended that roxadustat was taken after completion of the HD session. For participants treated with an erythropoietin analogue at study entry, selection of initial roxadustat dose was based on the participant's erythropoietin analogue dose at screening Visit 1. Participants not treated with an erythropoietin analogue at study entry initiated roxadustat using a tiered, weight-based dosing scheme. Doses were titrated to achieve and maintain Hb values of 11±1 g/dL. Dose adjustments were permitted starting at Week 4 and at intervals of every 4 weeks using a dose adjustment algorithm.	Epoetin Alfa n=1053 Participants Participants received epoetin alfa (only use of Procrit®, Eprex® and Epogen® permitted in the study) SC or IV injection TIW, except for participants treated with epoetin alfa in a less frequent regimen prior to study entry. For participants treated with an erythropoietin analogue at study entry, the initial dose of epoetin alfa was the actual dose administered at screening Visit 1. Participants treated with darbepoetin alfa or methoxy polyethylene glycol-epoetin beta prior to study entry initially received epoetin alfa at doses based on a conversion factor. For participants not treated with an erythropoietin analogue at study entry, the initial dose of epoetin alfa was 50 IU/kg TIW. Dose adjustments were to be consistent with local approved prescribing information.
Time-To-First Administration of RBC Transfusion as Rescue Therapy	6.0 events per 100 participant years	7.2 events per 100 participant years

Adverse Events

Roxadustat

Serious events: 604 serious events

Other events: 391 other events

Deaths: 247 deaths

Epoetin Alfa

Serious events: 606 serious events

Other events: 360 other events

Deaths: 231 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Roxadustat n=1048 participants at risk Participants received roxadustat tablets orally TIW throughout the treatment period (up to 4 years). For HD participants, it was recommended that roxadustat was taken after completion of the HD session. For participants treated with an erythropoietin analogue at study entry, selection of initial roxadustat dose was based on the participant's erythropoietin analogue dose at screening Visit 1. Participants not treated with an erythropoietin analogue at study entry initiated roxadustat using a tiered, weight-based dosing scheme. Doses were titrated to achieve and maintain Hb values of 11±1 g/dL. Dose adjustments were permitted starting at Week 4 and at intervals of every 4 weeks using a dose adjustment algorithm.	Epoetin Alfa n=1053 participants at risk Participants received epoetin alfa (only use of Procrit®, Eprex® and Epogen® permitted in the study) SC or IV injection TIW, except for participants treated with epoetin alfa in a less frequent regimen prior to study entry. For participants treated with an erythropoietin analogue at study entry, the initial dose of epoetin alfa was the actual dose administered at screening Visit 1. Participants treated with darbepoetin alfa or methoxy polyethylene glycol-epoetin beta prior to study entry initially received epoetin alfa at doses based on a conversion factor. For participants not treated with an erythropoietin analogue at study entry, the initial dose of epoetin alfa was 50 IU/kg TIW. Dose adjustments were to be consistent with local approved prescribing information.
Gastrointestinal disorders Diarrhoea	10.9% 114/1048 • Number of events 159 • From the first dose of IP administration (Day 1, Week 0) to 28 days after the last administration of the IP, with treatment duration up to 4 years. The on-treatment+28 days safety analysis set included all participants who received at least 1 dose of randomized IP, except for those excluded from analysis. Participants were censored at 28 days after the last administration of the IP. All-Cause Mortality represents all deaths due to any cause.	9.6% 101/1053 • Number of events 153 • From the first dose of IP administration (Day 1, Week 0) to 28 days after the last administration of the IP, with treatment duration up to 4 years. The on-treatment+28 days safety analysis set included all participants who received at least 1 dose of randomized IP, except for those excluded from analysis. Participants were censored at 28 days after the last administration of the IP. All-Cause Mortality represents all deaths due to any cause.
Gastrointestinal disorders Nausea	5.8% 61/1048 • Number of events 72 • From the first dose of IP administration (Day 1, Week 0) to 28 days after the last administration of the IP, with treatment duration up to 4 years. The on-treatment+28 days safety analysis set included all participants who received at least 1 dose of randomized IP, except for those excluded from analysis. Participants were censored at 28 days after the last administration of the IP. All-Cause Mortality represents all deaths due to any cause.	6.2% 65/1053 • Number of events 94 • From the first dose of IP administration (Day 1, Week 0) to 28 days after the last administration of the IP, with treatment duration up to 4 years. The on-treatment+28 days safety analysis set included all participants who received at least 1 dose of randomized IP, except for those excluded from analysis. Participants were censored at 28 days after the last administration of the IP. All-Cause Mortality represents all deaths due to any cause.
Gastrointestinal disorders Vomiting	5.7% 60/1048 • Number of events 69 • From the first dose of IP administration (Day 1, Week 0) to 28 days after the last administration of the IP, with treatment duration up to 4 years. The on-treatment+28 days safety analysis set included all participants who received at least 1 dose of randomized IP, except for those excluded from analysis. Participants were censored at 28 days after the last administration of the IP. All-Cause Mortality represents all deaths due to any cause.	4.9% 52/1053 • Number of events 64 • From the first dose of IP administration (Day 1, Week 0) to 28 days after the last administration of the IP, with treatment duration up to 4 years. The on-treatment+28 days safety analysis set included all participants who received at least 1 dose of randomized IP, except for those excluded from analysis. Participants were censored at 28 days after the last administration of the IP. All-Cause Mortality represents all deaths due to any cause.
Infections and infestations Bronchitis	4.1% 43/1048 • Number of events 67 • From the first dose of IP administration (Day 1, Week 0) to 28 days after the last administration of the IP, with treatment duration up to 4 years. The on-treatment+28 days safety analysis set included all participants who received at least 1 dose of randomized IP, except for those excluded from analysis. Participants were censored at 28 days after the last administration of the IP. All-Cause Mortality represents all deaths due to any cause.	5.8% 61/1053 • Number of events 95 • From the first dose of IP administration (Day 1, Week 0) to 28 days after the last administration of the IP, with treatment duration up to 4 years. The on-treatment+28 days safety analysis set included all participants who received at least 1 dose of randomized IP, except for those excluded from analysis. Participants were censored at 28 days after the last administration of the IP. All-Cause Mortality represents all deaths due to any cause.
Infections and infestations Upper respiratory tract infection	6.7% 70/1048 • Number of events 102 • From the first dose of IP administration (Day 1, Week 0) to 28 days after the last administration of the IP, with treatment duration up to 4 years. The on-treatment+28 days safety analysis set included all participants who received at least 1 dose of randomized IP, except for those excluded from analysis. Participants were censored at 28 days after the last administration of the IP. All-Cause Mortality represents all deaths due to any cause.	5.1% 54/1053 • Number of events 77 • From the first dose of IP administration (Day 1, Week 0) to 28 days after the last administration of the IP, with treatment duration up to 4 years. The on-treatment+28 days safety analysis set included all participants who received at least 1 dose of randomized IP, except for those excluded from analysis. Participants were censored at 28 days after the last administration of the IP. All-Cause Mortality represents all deaths due to any cause.
Nervous system disorders Headache	7.5% 79/1048 • Number of events 91 • From the first dose of IP administration (Day 1, Week 0) to 28 days after the last administration of the IP, with treatment duration up to 4 years. The on-treatment+28 days safety analysis set included all participants who received at least 1 dose of randomized IP, except for those excluded from analysis. Participants were censored at 28 days after the last administration of the IP. All-Cause Mortality represents all deaths due to any cause.	5.3% 56/1053 • Number of events 85 • From the first dose of IP administration (Day 1, Week 0) to 28 days after the last administration of the IP, with treatment duration up to 4 years. The on-treatment+28 days safety analysis set included all participants who received at least 1 dose of randomized IP, except for those excluded from analysis. Participants were censored at 28 days after the last administration of the IP. All-Cause Mortality represents all deaths due to any cause.
Respiratory, thoracic and mediastinal disorders Cough	5.8% 61/1048 • Number of events 77 • From the first dose of IP administration (Day 1, Week 0) to 28 days after the last administration of the IP, with treatment duration up to 4 years. The on-treatment+28 days safety analysis set included all participants who received at least 1 dose of randomized IP, except for those excluded from analysis. Participants were censored at 28 days after the last administration of the IP. All-Cause Mortality represents all deaths due to any cause.	5.9% 62/1053 • Number of events 76 • From the first dose of IP administration (Day 1, Week 0) to 28 days after the last administration of the IP, with treatment duration up to 4 years. The on-treatment+28 days safety analysis set included all participants who received at least 1 dose of randomized IP, except for those excluded from analysis. Participants were censored at 28 days after the last administration of the IP. All-Cause Mortality represents all deaths due to any cause.
Vascular disorders Hypertension	8.1% 85/1048 • Number of events 130 • From the first dose of IP administration (Day 1, Week 0) to 28 days after the last administration of the IP, with treatment duration up to 4 years. The on-treatment+28 days safety analysis set included all participants who received at least 1 dose of randomized IP, except for those excluded from analysis. Participants were censored at 28 days after the last administration of the IP. All-Cause Mortality represents all deaths due to any cause.	8.1% 85/1053 • Number of events 124 • From the first dose of IP administration (Day 1, Week 0) to 28 days after the last administration of the IP, with treatment duration up to 4 years. The on-treatment+28 days safety analysis set included all participants who received at least 1 dose of randomized IP, except for those excluded from analysis. Participants were censored at 28 days after the last administration of the IP. All-Cause Mortality represents all deaths due to any cause.
Vascular disorders Hypotension	6.1% 64/1048 • Number of events 79 • From the first dose of IP administration (Day 1, Week 0) to 28 days after the last administration of the IP, with treatment duration up to 4 years. The on-treatment+28 days safety analysis set included all participants who received at least 1 dose of randomized IP, except for those excluded from analysis. Participants were censored at 28 days after the last administration of the IP. All-Cause Mortality represents all deaths due to any cause.	5.1% 54/1053 • Number of events 83 • From the first dose of IP administration (Day 1, Week 0) to 28 days after the last administration of the IP, with treatment duration up to 4 years. The on-treatment+28 days safety analysis set included all participants who received at least 1 dose of randomized IP, except for those excluded from analysis. Participants were censored at 28 days after the last administration of the IP. All-Cause Mortality represents all deaths due to any cause.

Additional Information

Global Clinical Lead

AstraZeneca

Phone: +1 302 885 1180

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place