Trial Outcomes & Findings for Study to Evaluate the Efficacy and Safety of Roxadustat in the Treatment of Anemia in Participants With ESRD on Stable Dialysis (NCT NCT02273726)

Last Updated: 2021-10-29

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

741 participants

Primary outcome timeframe

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

Results posted on

2021-10-29

Participant Flow

Participants were randomized in a 1:1 ratio to receive either roxadustat or epoetin alfa.

Participant milestones

Participant milestones
Measure	Roxadustat Participants received roxadustat tablets, administered orally 3 times weekly (TIW). Initial roxadustat dose was 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 were permitted to maintain a hemoglobin (Hb) level of approximately 11 grams (g)/deciliter (dL). The maximum roxadustat dose was 3.0 milligrams (mg)/kilogram (kg) per dose or 400 mg per administration (whichever was lower). The maximum treatment duration was 183.7 weeks.	Epoetin Alfa Participants on hemodialysis (HD) received epoetin alfa, administered intravenously (IV) TIW and participants on home HD or peritoneal dialysis (PD) received epoetin alfa, administered subcutaneously (SC). Initial epoetin alfa dose was 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 was determined by the investigator per local standard of care (SOC). Dose adjustments followed the recommendations as per the approved country-specific product label (United States Package Insert \[USPI\] or Summary of Product Characteristics \[SmPC\]) or local SOC. The maximum treatment duration was 180.4 weeks.
Overall Study STARTED	370	371
Overall Study Received at Least 1 Dose of Study Drug	370	370
Overall Study COMPLETED	127	183
Overall Study NOT COMPLETED	243	188

Reasons for withdrawal

Reasons for withdrawal
Measure	Roxadustat Participants received roxadustat tablets, administered orally 3 times weekly (TIW). Initial roxadustat dose was 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 were permitted to maintain a hemoglobin (Hb) level of approximately 11 grams (g)/deciliter (dL). The maximum roxadustat dose was 3.0 milligrams (mg)/kilogram (kg) per dose or 400 mg per administration (whichever was lower). The maximum treatment duration was 183.7 weeks.	Epoetin Alfa Participants on hemodialysis (HD) received epoetin alfa, administered intravenously (IV) TIW and participants on home HD or peritoneal dialysis (PD) received epoetin alfa, administered subcutaneously (SC). Initial epoetin alfa dose was 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 was determined by the investigator per local standard of care (SOC). Dose adjustments followed the recommendations as per the approved country-specific product label (United States Package Insert \[USPI\] or Summary of Product Characteristics \[SmPC\]) or local SOC. The maximum treatment duration was 180.4 weeks.
Overall Study Death	70	62
Overall Study Withdrawal by Subject	41	29
Overall Study Kidney transplant	31	39
Overall Study Physician Decision	30	15
Overall Study Adverse Event	27	9
Overall Study Lost to Follow-up	6	3
Overall Study Lack of Efficacy	6	1
Overall Study Protocol Violation	4	0
Overall Study Other than specified	28	30

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Roxadustat n=370 Participants Participants received roxadustat tablets, administered orally TIW. Initial roxadustat dose was based on the participant's average prescribed ESA dose in the 4 weeks (if on epoetin or darbepoetin or 8 weeks (if on Mircera®) prior to randomization. Dose adjustments were permitted to maintain a Hb level of approximately 11 g/dL. The maximum roxadustat dose was 3.0 mg/kg per dose or 400 mg per administration (whichever was lower). The maximum treatment duration was 183.7 weeks.	Epoetin Alfa n=371 Participants Participants on HD received epoetin alfa, administered IV TIW and participants on home HD or PD received epoetin alfa, administered SC. Initial epoetin alfa dose was 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 was determined by the investigator per local SOC. Dose adjustments followed the recommendations as per the approved country-specific product label (USPI or SmPC) or local SOC. The maximum treatment duration was 180.4 weeks.	Total n=741 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	253 Participants n=93 Participants	246 Participants n=4 Participants	499 Participants n=27 Participants
Age, Categorical >=65 years	117 Participants n=93 Participants	125 Participants n=4 Participants	242 Participants n=27 Participants
Sex: Female, Male Female	183 Participants n=93 Participants	156 Participants n=4 Participants	339 Participants n=27 Participants
Sex: Female, Male Male	187 Participants n=93 Participants	215 Participants n=4 Participants	402 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	137 Participants n=93 Participants	129 Participants n=4 Participants	266 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	233 Participants n=93 Participants	242 Participants n=4 Participants	475 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race/Ethnicity, Customized Race · White	165 Participants n=93 Participants	184 Participants n=4 Participants	349 Participants n=27 Participants
Race/Ethnicity, Customized Race · Black/African American	158 Participants n=93 Participants	156 Participants n=4 Participants	314 Participants n=27 Participants
Race/Ethnicity, Customized Race · Asian	21 Participants n=93 Participants	15 Participants n=4 Participants	36 Participants n=27 Participants
Race/Ethnicity, Customized Race · American Indian/Alaskan Native	10 Participants n=93 Participants	7 Participants n=4 Participants	17 Participants n=27 Participants
Race/Ethnicity, Customized Race · Native Hawaiian or Other Pacific Islander	1 Participants n=93 Participants	3 Participants n=4 Participants	4 Participants n=27 Participants
Race/Ethnicity, Customized Race · Other	15 Participants n=93 Participants	6 Participants n=4 Participants	21 Participants n=27 Participants

PRIMARY outcome

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

Population: ITT Population included all randomized participants.

Outcome measures

Outcome measures
Measure	Roxadustat n=370 Participants Participants received roxadustat tablets, administered orally TIW. Initial roxadustat dose was based on the participant's average prescribed ESA dose in the 4 weeks (if on epoetin or darbepoetin or 8 weeks (if on Mircera®) prior to randomization. Dose adjustments were permitted to maintain a Hb level of approximately 11 g/dL. The maximum roxadustat dose was 3.0 mg/kg per dose or 400 mg per administration (whichever was lower). The maximum treatment duration was 183.7 weeks.	Epoetin Alfa n=371 Participants Participants on HD received epoetin alfa, administered IV TIW and participants on home HD or PD received epoetin alfa, administered SC. Initial epoetin alfa dose was 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 was determined by the investigator per local SOC. Dose adjustments followed the recommendations as per the approved country-specific product label (USPI or SmPC) or local SOC. The maximum treatment duration was 180.4 weeks.
US (FDA) Submission: Mean Hb Change From Baseline to The Average Level During The Evaluation Period (Weeks 28 to 52), Regardless of Rescue Therapy Baseline	10.30 g/dL Standard Deviation 0.661	10.31 g/dL Standard Deviation 0.656
US (FDA) Submission: Mean Hb Change From Baseline to The Average Level During The Evaluation Period (Weeks 28 to 52), Regardless of Rescue Therapy Change at Weeks 28 to 52	0.39 g/dL Standard Deviation 0.934	-0.09 g/dL Standard Deviation 0.838

PRIMARY outcome

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

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Roxadustat n=303 Participants Participants received roxadustat tablets, administered orally TIW. Initial roxadustat dose was based on the participant's average prescribed ESA dose in the 4 weeks (if on epoetin or darbepoetin or 8 weeks (if on Mircera®) prior to randomization. Dose adjustments were permitted to maintain a Hb level of approximately 11 g/dL. The maximum roxadustat dose was 3.0 mg/kg per dose or 400 mg per administration (whichever was lower). The maximum treatment duration was 183.7 weeks.	Epoetin Alfa n=324 Participants Participants on HD received epoetin alfa, administered IV TIW and participants on home HD or PD received epoetin alfa, administered SC. Initial epoetin alfa dose was 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 was determined by the investigator per local SOC. Dose adjustments followed the recommendations as per the approved country-specific product label (USPI or SmPC) or local SOC. The maximum treatment duration was 180.4 weeks.
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 Change at Weeks 28 to 36	0.54 g/dL Standard Deviation 1.022	-0.03 g/dL Standard Deviation 0.897
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 Baseline	10.33 g/dL Standard Deviation 0.639	10.35 g/dL Standard Deviation 0.614

SECONDARY outcome

Timeframe: Weeks 28 to 52

Population: FAS population included all randomized participants who received at least 1 dose of study drug and had at least 1 postdose Hb assessment.

Outcome measures

Outcome measures
Measure	Roxadustat n=369 Participants Participants received roxadustat tablets, administered orally TIW. Initial roxadustat dose was based on the participant's average prescribed ESA dose in the 4 weeks (if on epoetin or darbepoetin or 8 weeks (if on Mircera®) prior to randomization. Dose adjustments were permitted to maintain a Hb level of approximately 11 g/dL. The maximum roxadustat dose was 3.0 mg/kg per dose or 400 mg per administration (whichever was lower). The maximum treatment duration was 183.7 weeks.	Epoetin Alfa n=370 Participants Participants on HD received epoetin alfa, administered IV TIW and participants on home HD or PD received epoetin alfa, administered SC. Initial epoetin alfa dose was 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 was determined by the investigator per local SOC. Dose adjustments followed the recommendations as per the approved country-specific product label (USPI or SmPC) or local SOC. The maximum treatment duration was 180.4 weeks.
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	66.1 percentage of participants	58.6 percentage of participants

SECONDARY outcome

Timeframe: Weeks 28 to 36

Population: The PPS population included all participants in the 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, had at least 1 valid postdose Hb assessment and were without major protocol violations.

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.

Outcome measures

Outcome measures
Measure	Roxadustat n=334 Participants Participants received roxadustat tablets, administered orally TIW. Initial roxadustat dose was based on the participant's average prescribed ESA dose in the 4 weeks (if on epoetin or darbepoetin or 8 weeks (if on Mircera®) prior to randomization. Dose adjustments were permitted to maintain a Hb level of approximately 11 g/dL. The maximum roxadustat dose was 3.0 mg/kg per dose or 400 mg per administration (whichever was lower). The maximum treatment duration was 183.7 weeks.	Epoetin Alfa n=352 Participants Participants on HD received epoetin alfa, administered IV TIW and participants on home HD or PD received epoetin alfa, administered SC. Initial epoetin alfa dose was 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 was determined by the investigator per local SOC. Dose adjustments followed the recommendations as per the approved country-specific product label (USPI or SmPC) or local SOC. The maximum treatment duration was 180.4 weeks.
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	64.1 percentage of participants	60.8 percentage of participants

SECONDARY outcome

Timeframe: Baseline (Day 1, Week 0), Weeks 12 to 28

Population: FAS population included all randomized participants who received at least 1 dose of study drug and had at least 1 postdose Hb assessment. Here, 'Number analyzed' signifies participants evaluable for this outcome measure at specified timepoint.

Baseline LDL Cholesterol was defined as the last available value prior to the first dose of study treatment.

Outcome measures

Outcome measures
Measure	Roxadustat n=369 Participants Participants received roxadustat tablets, administered orally TIW. Initial roxadustat dose was based on the participant's average prescribed ESA dose in the 4 weeks (if on epoetin or darbepoetin or 8 weeks (if on Mircera®) prior to randomization. Dose adjustments were permitted to maintain a Hb level of approximately 11 g/dL. The maximum roxadustat dose was 3.0 mg/kg per dose or 400 mg per administration (whichever was lower). The maximum treatment duration was 183.7 weeks.	Epoetin Alfa n=370 Participants Participants on HD received epoetin alfa, administered IV TIW and participants on home HD or PD received epoetin alfa, administered SC. Initial epoetin alfa dose was 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 was determined by the investigator per local SOC. Dose adjustments followed the recommendations as per the approved country-specific product label (USPI or SmPC) or local SOC. The maximum treatment duration was 180.4 weeks.
Change From Baseline in Low-Density Lipoprotein (LDL) Cholesterol Averaged Over Weeks 12 to 28 Baseline	84.53 mg/dL Standard Deviation 34.009	84.45 mg/dL Standard Deviation 34.124
Change From Baseline in Low-Density Lipoprotein (LDL) Cholesterol Averaged Over Weeks 12 to 28 Change at Weeks 12 to 28	-13.70 mg/dL Standard Deviation 23.068	1.23 mg/dL Standard Deviation 22.389

SECONDARY outcome

Timeframe: Baseline (Day 1, Week 0), Weeks 18 to 24

Population: FAS population included all randomized participants who received at least 1 dose of study drug and had at least 1 postdose Hb assessment. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.

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.

Outcome measures

Outcome measures
Measure	Roxadustat n=189 Participants Participants received roxadustat tablets, administered orally TIW. Initial roxadustat dose was based on the participant's average prescribed ESA dose in the 4 weeks (if on epoetin or darbepoetin or 8 weeks (if on Mircera®) prior to randomization. Dose adjustments were permitted to maintain a Hb level of approximately 11 g/dL. The maximum roxadustat dose was 3.0 mg/kg per dose or 400 mg per administration (whichever was lower). The maximum treatment duration was 183.7 weeks.	Epoetin Alfa n=176 Participants Participants on HD received epoetin alfa, administered IV TIW and participants on home HD or PD received epoetin alfa, administered SC. Initial epoetin alfa dose was 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 was determined by the investigator per local SOC. Dose adjustments followed the recommendations as per the approved country-specific product label (USPI or SmPC) or local SOC. The maximum treatment duration was 180.4 weeks.
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) Baseline	10.30 g/dL Standard Deviation 0.616	10.24 g/dL Standard Deviation 0.630
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) Change at Weeks 18-24	0.61 g/dL Standard Deviation 1.020	-0.03 g/dL Standard Deviation 0.940

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Roxadustat n=286 Participants Participants received roxadustat tablets, administered orally TIW. Initial roxadustat dose was based on the participant's average prescribed ESA dose in the 4 weeks (if on epoetin or darbepoetin or 8 weeks (if on Mircera®) prior to randomization. Dose adjustments were permitted to maintain a Hb level of approximately 11 g/dL. The maximum roxadustat dose was 3.0 mg/kg per dose or 400 mg per administration (whichever was lower). The maximum treatment duration was 183.7 weeks.	Epoetin Alfa n=319 Participants Participants on HD received epoetin alfa, administered IV TIW and participants on home HD or PD received epoetin alfa, administered SC. Initial epoetin alfa dose was 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 was determined by the investigator per local SOC. Dose adjustments followed the recommendations as per the approved country-specific product label (USPI or SmPC) or local SOC. The maximum treatment duration was 180.4 weeks.
Average Monthly IV Iron Use Per Patient-Exposure-Month (PEM) During Weeks 28 to 52	17.07 mg/PEM Standard Deviation 53.375	37.02 mg/PEM Standard Deviation 106.778

SECONDARY outcome

Timeframe: 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)

Population: FAS population included all randomized participants who received at least 1 dose of study drug and had at least 1 postdose Hb assessment.

Median time to event (weeks) was calculated using Kaplan Meier Survival Estimates.

Outcome measures

Outcome measures
Measure	Roxadustat n=369 Participants Participants received roxadustat tablets, administered orally TIW. Initial roxadustat dose was based on the participant's average prescribed ESA dose in the 4 weeks (if on epoetin or darbepoetin or 8 weeks (if on Mircera®) prior to randomization. Dose adjustments were permitted to maintain a Hb level of approximately 11 g/dL. The maximum roxadustat dose was 3.0 mg/kg per dose or 400 mg per administration (whichever was lower). The maximum treatment duration was 183.7 weeks.	Epoetin Alfa n=370 Participants Participants on HD received epoetin alfa, administered IV TIW and participants on home HD or PD received epoetin alfa, administered SC. Initial epoetin alfa dose was 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 was determined by the investigator per local SOC. Dose adjustments followed the recommendations as per the approved country-specific product label (USPI or SmPC) or local SOC. The maximum treatment duration was 180.4 weeks.
Time to First RBC Transfusion	NA weeks Due to smaller number of participants with an event (any use of RBC transfusion), median and 95% CI could not be calculated.	NA weeks Due to smaller number of participants with an event (any use of RBC transfusion), median and 95% CI could not be calculated.

SECONDARY outcome

Timeframe: Baseline (Day 1, Week 0), 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.

Outcome measures

Outcome measures
Measure	Roxadustat n=369 Participants Participants received roxadustat tablets, administered orally TIW. Initial roxadustat dose was based on the participant's average prescribed ESA dose in the 4 weeks (if on epoetin or darbepoetin or 8 weeks (if on Mircera®) prior to randomization. Dose adjustments were permitted to maintain a Hb level of approximately 11 g/dL. The maximum roxadustat dose was 3.0 mg/kg per dose or 400 mg per administration (whichever was lower). The maximum treatment duration was 183.7 weeks.	Epoetin Alfa n=370 Participants Participants on HD received epoetin alfa, administered IV TIW and participants on home HD or PD received epoetin alfa, administered SC. Initial epoetin alfa dose was 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 was determined by the investigator per local SOC. Dose adjustments followed the recommendations as per the approved country-specific product label (USPI or SmPC) or local SOC. The maximum treatment duration was 180.4 weeks.
Change From Baseline in Mean Arterial Pressure (MAP) Averaged Over Weeks 20 to 28 Baseline	101.41 millimeters of mercury (mmHg) Standard Deviation 12.591	100.34 millimeters of mercury (mmHg) Standard Deviation 12.350
Change From Baseline in Mean Arterial Pressure (MAP) Averaged Over Weeks 20 to 28 Change at Weeks 20 to 28	0.46 millimeters of mercury (mmHg) Standard Deviation 10.933	0.04 millimeters of mercury (mmHg) Standard Deviation 10.489

SECONDARY outcome

Timeframe: Weeks 28 to 52

Population: FAS population included all randomized participants who received at least 1 dose of study drug and had at least 1 postdose Hb assessment.

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.

Outcome measures

Outcome measures
Measure	Roxadustat n=369 Participants Participants received roxadustat tablets, administered orally TIW. Initial roxadustat dose was based on the participant's average prescribed ESA dose in the 4 weeks (if on epoetin or darbepoetin or 8 weeks (if on Mircera®) prior to randomization. Dose adjustments were permitted to maintain a Hb level of approximately 11 g/dL. The maximum roxadustat dose was 3.0 mg/kg per dose or 400 mg per administration (whichever was lower). The maximum treatment duration was 183.7 weeks.	Epoetin Alfa n=370 Participants Participants on HD received epoetin alfa, administered IV TIW and participants on home HD or PD received epoetin alfa, administered SC. Initial epoetin alfa dose was 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 was determined by the investigator per local SOC. Dose adjustments followed the recommendations as per the approved country-specific product label (USPI or SmPC) or local SOC. The maximum treatment duration was 180.4 weeks.
Time to First Exacerbation of Hypertension During Weeks 28 to 52	NA weeks Due to smaller number of participants with an event (exacerbation hypertension), median and 95% CI could not be calculated.	NA weeks Due to smaller number of participants with an event (exacerbation hypertension), median and 95% CI could not be calculated.

SECONDARY outcome

Timeframe: Baseline (Day 1, Week 0), Weeks 12 to 28

Population: FAS Population included all randomized/enrolled participants who received at least 1 dose of study drug and had baseline and at least 1 postdose Hb assessment. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure and 'Number Analyzed' signifies participants evaluable for this outcome measure at specified timepoint.

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.

Outcome measures

Outcome measures
Measure	Roxadustat n=368 Participants Participants received roxadustat tablets, administered orally TIW. Initial roxadustat dose was based on the participant's average prescribed ESA dose in the 4 weeks (if on epoetin or darbepoetin or 8 weeks (if on Mircera®) prior to randomization. Dose adjustments were permitted to maintain a Hb level of approximately 11 g/dL. The maximum roxadustat dose was 3.0 mg/kg per dose or 400 mg per administration (whichever was lower). The maximum treatment duration was 183.7 weeks.	Epoetin Alfa n=369 Participants Participants on HD received epoetin alfa, administered IV TIW and participants on home HD or PD received epoetin alfa, administered SC. Initial epoetin alfa dose was 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 was determined by the investigator per local SOC. Dose adjustments followed the recommendations as per the approved country-specific product label (USPI or SmPC) or local SOC. The maximum treatment duration was 180.4 weeks.
Change From Baseline in Short Form 36 (SF-36) Version 2 Physical Functioning Subscore and Vitality Subscore at Weeks 12 to 28 Physical functioning subscore: Baseline	38.55 score on a scale Standard Deviation 11.202	39.63 score on a scale Standard Deviation 11.368
Change From Baseline in Short Form 36 (SF-36) Version 2 Physical Functioning Subscore and Vitality Subscore at Weeks 12 to 28 Physical functioning subscore: Change at Weeks 12 to 28	-0.15 score on a scale Standard Deviation 7.443	-0.20 score on a scale Standard Deviation 6.380
Change From Baseline in Short Form 36 (SF-36) Version 2 Physical Functioning Subscore and Vitality Subscore at Weeks 12 to 28 Vitality subscore: Baseline	51.65 score on a scale Standard Deviation 10.111	51.27 score on a scale Standard Deviation 9.841
Change From Baseline in Short Form 36 (SF-36) Version 2 Physical Functioning Subscore and Vitality Subscore at Weeks 12 to 28 Vitality subscore: Change at Weeks 12 to 28	-0.92 score on a scale Standard Deviation 7.007	0.30 score on a scale Standard Deviation 7.041

Adverse Events

Roxadustat

Serious events: 242 serious events

Other events: 286 other events

Deaths: 70 deaths

Epoetin Alfa

Serious events: 248 serious events

Other events: 292 other events

Deaths: 62 deaths

Serious adverse events

Other adverse events

Additional Information

Clinical Trial Information Desk

FibroGen, Inc.

Phone: 415-978-1441

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The multisite consortium can publish any time after the data is collected and analyzed by FibroGen. The investigator can only publish after the multisite consortium publishes (or tries to publish and fails). FibroGen has 60 days to review a publication and can extend the embargo up to an additional 120 days (or 180 total).
Publication restrictions are in place

Restriction type: OTHER