Anemia
Conditions
Keywords
Renal,, CKD,, Epoetin alfa,, Roxadustat,, dialysis,, anemia
Brief summary
The purpose of this study is to evaluate the efficacy and safety of roxadustat compared to epoetin alfa for the treatment of anemia in chronic kidney disease patients on dialysis.
Detailed description
This is a Phase 3, multicenter, randomized, open-label, active-controlled study to evaluate the efficacy and safety of roxadustat compared to epoetin alfa for the treatment of anemia in dialysis patients. Patients on hemodialysis (HD) or peritoneal dialysis (PD) who have been treated with an erythropoietin analogue or have an indication for treatment with an erythropoietin analogue will be evaluated for eligibility and randomized at a 1:1 ratio to treatment with roxadustat (with discontinuation of prior erythropoietin analogue therapy) or to an active-control group treated with epoetin alfa
Interventions
DRUGRoxadustat
Roxadustat will be administered orally three times a week (TIW) to achieve an Hb level of 11 g/dL and maintain a Hb level of 11±1 g/dL.
DRUGEpoetin alfa
Epoetin alfa will be administered TIW consistent with approved prescribing information for epoetin alfa to achieve an Hb level of 11 g/dL and maintain a Hb level of 11±1 g/dL.
Sponsors
FibroGen
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 130 Years
Healthy volunteers
No
Inclusion criteria
1. Provision of Informed Consent prior to any study specific procedures 2. Age ≥18 years at screening visit 1 3. Previous versions of the protocol prior to US amendment ver 6.0 and outside of US amendment ver 7.0: Receiving or initiating hemodialysis or peritoneal dialysis for treatment of native kidney end-stage renal disease (ESRD) at least 30 days prior to visit 1. Patients treated with hemodialysis must have access consisting of an arteriovenous fistula, AV graft, or tunneled (permanent) catheter. Patients on peritoneal dialysis must have a functioning peritoneal dialysis catheter in place. Starting with US amendment ver. 6.0 and outside of US amendment ver 7.0 (changed to recruit incident dialysis patients only): Receiving or initiating hemodialysis or peritoneal dialysis for treatment of native kidney end-stage renal disease (ESRD) for a minimum of 2 weeks and a maximum of 4 months prior to randomization. Patients treated with hemodialysis must have access consisting of an arteriovenous fistula, AV graft, or tunneled (permanent) catheter. Patients on peritoneal dialysis must have a functioning peritoneal dialysis catheter in place. 4. Two central laboratory Hb values during the screening period, obtained at least 7 days apart, must be \<12 g/dL in patients currently treated with an erythropoietin analogue or \<10 g/dL in patients not currently treated with an erythropoietin analogue. Patients are considered not currently treated if they have not received either Mircera® for at least 8 weeks or any other erythropoietin analogue for at least 4 weeks prior to visit 1. 5. Ferritin ≥100 ng/mL at randomization (obtained from screening visit) 6. TSAT ≥20% at randomization (obtained from screening visit) 7. Serum folate level ≥ lower limit of normal (LLN) at randomization (obtained from screening visit) 8. Serum vitamin B12 level ≥ LLN at randomization (obtained from screening visit) 9. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3x upper limit of normal (ULN), and total bilirubin (Tbili) ≤1.5 x ULN at randomization (obtained from screening visit) 10. Body weight 45 to 160 kg (prescribed dry weight)
Exclusion criteria
1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site) 2. Previous randomisation in the present study 3. New York Heart Association Class III or IV congestive heart failure at enrolment 4. Myocardial infarction, acute coronary syndrome, stroke, seizure or a thrombotic/thromboembolic event (e.g., deep vein thrombosis or pulmonary embolism) within 12 weeks prior to randomization 5. History of chronic liver disease (e.g., chronic infectious hepatitis, chronic auto-immune liver disease, cirrhosis or fibrosis of the liver) 6. Known hereditary hematologic disease such as thalassemia, sickle cell anemia, a history of pure red cell aplasia or other known causes for anemia other than CKD 7. Known and untreated retinal vein occlusion or known and untreated proliferative diabetic retinopathy (risk for retinal vein thrombosis) 8. Diagnosis or suspicion (e.g. complex kidney cyst of Bosniak Category IIF, III or IV) of renal cell carcinoma on renal ultrasound (or other imaging procedure e.g. CT scan or MRI) conducted at screening or within 12 weeks prior to randomization. 9. Uncontrolled hypertension at the time of randomization (defined as systolic BP ≥180 mmHg or diastolic BP ≥100 mmHg on repeated measurement post-dialysis in hemodialysis patients or at any time in peritoneal dialysis patients), contraindication to epoetin alfa treatment (e.g., pure red cell aplasia, hypersensitivity or know inability to tolerate epoetin alfa) 10. History of prostate cancer, breast cancer or any other malignancy, except the following: cancers determined to be cured or in remission for ≥5 years, curatively resected basal cell or squamous cell skin cancers, cervical cancer in situ or resected colonic polyps. 11. Positive for any of the following: human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or anti-hepatitis C virus antibody (anti-HCV Ab) 12. Chronic inflammatory diseases such as rheumatoid arthritis, SLE, ankylosing spondylitis, psoriatic arthritis or inflammatory bowel disease that is determined to be the principal cause of anemia 13. Known hemosiderosis, hemochromatosis or hypercoagulable condition 14. Any prior organ transplant with the exception of an autologous renal transplant or a renal transplant that was subsequently removed (explanted) or scheduled organ transplantation date 15. Any red blood cell (RBC) transfusion during the screening period 16. Any current condition leading to active significant blood loss 17. Any prior treatment with roxadustat or a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) 18. Has received another new chemical entity (defined as a compound which has not been approved for marketing) or has participated in any other clinical study that included drug treatment within the month preceding the first administration of IP in this study. (Note: patients consented and screened, but not randomized in this study or a previous study are not excluded) 19. History of alcohol or drug abuse within 2 years prior to randomization 20. Females of childbearing potential, unless using contraception as detailed in the protocol or sexual abstinence (see Section 3.8) 21. Pregnant or breastfeeding females 22. Known allergy to the investigational product or any of its ingredients 23. Any medical condition, including active, clinically significant infection, that in the opinion of the investigator or Sponsor may pose a safety risk to a patient in this study, which may confound efficacy or safety assessment, or may interfere with study participation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Hb Averaged Over Week 28 to Week 52 | Baseline (Day 1, Week 0), Week 28 to 52 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Total Time of Hb Within the Interval of >=10 g/dL From Week 28 to Week 52 | 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 \>=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. |
| Proportion of Total Time of Hb Within the Interval of 10 to 12 g/dL From Week 28 to Week 52 | 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. |
| Mean Change in Low-Density Lipoprotein (LDL) Cholesterol From Baseline to Week 24 | 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. |
| 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 | Baseline (Day 1, Week 0), Week 28 to 36 | 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. |
| Mean Monthly IV Iron Use From Week 36 to End of Study (EOS) | 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%). |
| Time-To-First Administration of RBC Transfusion as Rescue Therapy | Baseline (Day 1, Week 0) up to EOS (4 weeks after the treatment period) | 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. |
| 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) | Baseline (Day 1, Week 0), Week 28 to 52 | 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. |
Countries
Australia, Bulgaria, Canada, Czechia, Hungary, India, Mexico, Peru, Philippines, Poland, Russia, Slovakia, Spain, Sweden, Thailand, Ukraine, United States, Vietnam
Participant flow
Recruitment details
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.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Roxadustat 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. | 1,051 |
| Epoetin Alfa 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. | 1,055 |
| Total | 2,106 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Incorrect enrolment before randomization | 0 | 1 |
| Overall Study | Missing | 2 | 0 |
| Overall Study | Participant decision | 67 | 64 |
Baseline characteristics
| Characteristic | Roxadustat | Total | Epoetin Alfa |
|---|---|---|---|
| Age, Continuous | 53.5 years STANDARD_DEVIATION 15.3 | 54.0 years STANDARD_DEVIATION 15.14 | 54.5 years STANDARD_DEVIATION 14.97 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 268 Participants | 539 Participants | 271 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 783 Participants | 1567 Participants | 784 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 50 Participants | 112 Participants | 62 Participants |
| Race/Ethnicity, Customized Asian | 208 Participants | 406 Participants | 198 Participants |
| Race/Ethnicity, Customized Black of African American | 148 Participants | 306 Participants | 158 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 5 Participants | 8 Participants | 3 Participants |
| Race/Ethnicity, Customized Other | 43 Participants | 79 Participants | 36 Participants |
| Race/Ethnicity, Customized White | 597 Participants | 1195 Participants | 598 Participants |
| Sex: Female, Male Female | 426 Participants | 855 Participants | 429 Participants |
| Sex: Female, Male Male | 625 Participants | 1251 Participants | 626 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 247 / 1,048 | 231 / 1,053 |
| other Total, other adverse events | 391 / 1,048 | 360 / 1,053 |
| serious Total, serious adverse events | 604 / 1,048 | 606 / 1,053 |
Outcome results
Primary
Mean Change From Baseline in Hb Averaged Over Week 28 to Week 52
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Roxadustat | Mean Change From Baseline in Hb Averaged Over Week 28 to Week 52 | 0.77 g/dL | Standard Error 0.041 |
| Epoetin Alfa | Mean Change From Baseline in Hb Averaged Over Week 28 to Week 52 | 0.68 g/dL | Standard Error 0.04 |
p-value: <0.00195% CI: [0.01, 0.18]ANCOVA
Secondary
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
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Roxadustat | 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 |
| Epoetin Alfa | 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 | 0.74 g/dL | Standard Error 0.043 |
p-value: <0.00195% CI: [0.03, 0.25]MMRM
Secondary
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)
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Roxadustat | 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 |
| Epoetin Alfa | 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) | 0.59 g/dL | Standard Error 0.076 |
p-value: <0.00195% CI: [0.04, 0.36]ANCOVA
Secondary
Mean Change in Low-Density Lipoprotein (LDL) Cholesterol From Baseline 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.
Time frame: Baseline (Day 1, Week 0) to Week 24
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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Roxadustat | Mean Change in Low-Density Lipoprotein (LDL) Cholesterol From Baseline to Week 24 | -0.38 millimole per liter | Standard Error 0.026 |
| Epoetin Alfa | Mean Change in Low-Density Lipoprotein (LDL) Cholesterol From Baseline to Week 24 | -0.05 millimole per liter | Standard Error 0.026 |
p-value: <0.00195% CI: [-0.39, -0.27]ANCOVA
Secondary
Mean Monthly IV Iron Use From Week 36 to End of Study (EOS)
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%).
Time frame: Week 36 to EOS (4 weeks after the treatment period)
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Roxadustat | Mean Monthly IV Iron Use From Week 36 to End of Study (EOS) | 58.71 milligram per month | Standard Deviation 236.12 |
| Epoetin Alfa | Mean Monthly IV Iron Use From Week 36 to End of Study (EOS) | 91.37 milligram per month | Standard Deviation 225.64 |
p-value: <0.0001Wilcoxon Rank Sum Test
Secondary
Proportion of Total Time of Hb Within the Interval of >=10 g/dL From Week 28 to Week 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 \>=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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Roxadustat | 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 |
| Epoetin Alfa | Proportion of Total Time of Hb Within the Interval of >=10 g/dL From Week 28 to Week 52 | 0.76 proportion of total time | Standard Error 0.012 |
p-value: <0.00195% CI: [0, 0.05]ANCOVA
Secondary
Proportion of Total Time of Hb Within the Interval of 10 to 12 g/dL From Week 28 to Week 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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Roxadustat | 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 |
| Epoetin Alfa | Proportion of Total Time of Hb Within the Interval of 10 to 12 g/dL From Week 28 to Week 52 | 0.63 proportion of total time | Standard Error 0.012 |
p-value: <0.00195% CI: [-0.01, 0.05]ANCOVA
Secondary
Time-To-First Administration of RBC Transfusion as Rescue Therapy
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Roxadustat | Time-To-First Administration of RBC Transfusion as Rescue Therapy | 6.0 events per 100 participant years |
| Epoetin Alfa | Time-To-First Administration of RBC Transfusion as Rescue Therapy | 7.2 events per 100 participant years |
p-value: <0.00195% CI: [0.64, 1.07]Regression, Cox