Anemia, End Stage Renal Disease (ESRD)
Conditions
Keywords
ASP1517, FG-4592, Anemia, End Stage Renal Disease (ESRD), Erythropoetin Stimulating Agents (ESAs), Chronic Kidney Disease, Hematopoetic Agents, HIF-PH inhibitor, Hemoglobin, Dialysis, roxadustat
Brief summary
This study was conducted to explore a new therapy for anemia in participants with end stage renal disease (ESRD) on dialysis. Anemia is a reduced number of red blood cells or hemoglobin. Hemoglobin (which contains iron) is important for the transport of oxygen in your blood. The purpose of this study was to evaluate if roxadustat is effective and safe in the maintenance treatment of anemia in ESRD participants on stable dialysis. Roxadustat was compared to epoetin alfa and darbepoetin alfa, commercially available medicines for treatment of anemia.
Detailed description
This study consisted of three study periods as follows: * Screening Period: up to 6 weeks * Treatment Period: a minimum of 52 weeks up to a maximum of 104 weeks * Follow-up Period: 4 weeks
Interventions
DRUGRoxadustat
Participants received initial dose of roxadustat orally as a tablet in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met.
DRUGEpoetin alfa
Participants received epoetin alfa via intravenous or subcutaneous injection, once a week, twice a week, or three times a week (TIW). Epoetin alfa dosage was adjusted to maintain Hb level within the target range. Dosing of epoetin alfa was per UK SmPC of Eprex®. Participants received IV iron supplementation according to the standard of care.
DRUGDarbepoetin alfa
Participants received darbepoetin alfa via intravenous or subcutaneous injection, once a week or once every other week. Darbepoetin alfa dosage was adjusted to maintain Hb level within the target range. Dosing of darbepoetin alfa was per EU SmPC of Aranesp®. Participants received IV iron supplementation according to the standard of care.
DRUGIron
Oral iron treatment was recommended for supplementation to support erythropoiesis and as first-line treatment for iron deficiency, unless participant was intolerant to this treatment. For participants receiving roxadustat the recommended daily dose was 200 mg of elemental iron. Participants were advised to take roxadustat at least 1 hour before or 1 hour after oral iron. Intravenous iron supplementation for participants receiving roxadustat was allowed if all of the following criteria were met: The participant's Hb level had not responded adequately to roxadustat following two consecutive dose increases or reached the maximum dose limit, and participant's ferritin was \< 100 ng/mL (\< 220 pmol/L) or TSAT \< 20%, or the participant was intolerant of oral iron therapy. For participants treated with epoetin alfa or darbepoetin alfa, IV iron supplementation was given according to standard of care.
Sponsors
Kyntra Bio
Astellas Pharma Europe B.V.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Main Inclusion: * Participant is on stable hemodialysis (HD), hemodiafiltration (HDF) or peritoneal dialysis (PD) treatment with the same mode of dialysis for ≥4 months prior to randomization. * Participant is on IV or SC epoetin or IV or SC darbepoetin alfa treatment for ≥8 weeks prior to randomization with stable weekly doses (during 4 weeks prior to randomization). * Mean of the participant's three most recent Hb values, as measured by central laboratory, during the Screening Period. * Participant's alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are ≤3 x upper limit of normal (ULN), and total bilirubin (TBL) is ≤1.5 x ULN
Exclusion criteria
Main Exclusion: * Participant has received a red blood cell (RBC) transfusion within 8 weeks prior to randomization. * Participant has a known hereditary hematologic disease such as thalassemia or sickle cell anemia, pure red cell aplasia, or other known causes for anemia other than Chronic Kidney Disease (CKD). * Participant has had a myocardial infarction, acute coronary syndrome, stroke, seizure, or a thrombotic/thrombo-embolic event (e.g., deep vein thrombosis or pulmonary embolism) within 12 weeks prior to randomization. * Participant has had uncontrolled hypertension, in the opinion of the investigator, within 2 weeks prior to randomization. * Participant has a history of malignancy, except for 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. * Participant has had any prior organ transplant (that has not been explanted), or participant is scheduled for organ transplantation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline (BL) to the Average Hemoglobin (Hb) in Weeks 28-36 Without Rescue Therapy [EU (EMA)] | Baseline and weeks 28 to 36 | Baseline Hb was defined as the mean of four central laboratory Hb values; four latest Hb values prior or on the same date as the first study drug intake. For participants who did not have an available Hb value during the week 28-36 period, imputation rules were applied. For analyses without rescue therapy, participants who used rescue therapy after the initiation of rescue therapy were set to missing for 6 weeks from the start date of rescue therapy. If no Hb value was available, an imputation technique was used, with the mean of all available values from Day 1 to minimum (End of Efficacy Emergent Period) carried forward. |
| Change From BL to the Average Hb in Weeks 28 to 52 Regardless of Rescue Therapy [US (FDA)] | Baseline and weeks 28 to 52 | Baseline Hb was defined as the mean of four central laboratory Hb values: four latest Hb values prior or on the same date as first study drug intake. Change from baseline to the average Hb are observed values. Missing hemoglobin 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 with treatment, baseline hemoglobin, randomization stratification factors and the available non missing hemoglobin for each scheduled week. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Monthly Intravenous (IV) Iron Use | Day 1 to week 36 | Participants with no or missing medication records of IV Iron have their monthly IV Iron use set to 0 mg. For participants who took IV Iron, but without a dosing frequency, the average values were set to missing. |
| Change From BL in Short Form-36 (SF-36) Health Survey Physical Functioning (PF) Sub-score to the Average of Weeks 12 to 28 | Baseline and weeks 12 to 28 | Baseline SF-36 PF was defined as the SF-36 PF value on Day 1.The SF-36 is a Quality of Life (QoL) instrument designed to assess generic health concepts relevant across age, disease, and treatment groups. The SF-36 contains 36 items that measure eight scales: (1) physical functioning (PF); (2) role limitations due to physical health problems (RP); (3) bodily pain (BP); (4) social functioning (SF); (5) general health perceptions (GH); (6) role limitations due to emotional problems (RE); (7) vitality, energy or fatigue (VT); and (8) mental health(MH). Each scale is transformed into 0-100 score, with higher scores indicating better health status. The SF-36 PF consists of 11 questions focused on health and ability to do usual activities, with higher scores indicating better health status. |
| Change From BL in SF-36 Vitality (VT) Sub-score to the Average of Weeks 12 to 28 | Baseline and weeks 12 to 28 | Baseline VT Subscore was defined as the VT value on Day 1. The SF-36 is a QoL instrument designed to assess generic health concepts relevant across age, disease, and treatment groups. The SF-36 vitality has four questions with score range from 0-100 with higher scores indicating better vitality status. |
| Change From BL in Mean Arterial Pressure (MAP) to the Average of Weeks 20 to 28 | Baseline and weeks 20 to 28 | Baseline MAP was defined as the MAP value on Day 1. If this value was missing, the latest value prior to first study drug administration was used. Mean Arterial Pressure (MAP) is derived as: MAP = (2/3)\*DBP + (1/3)\*SBP. |
| Time to First Occurrence of an Increase in Blood Pressure | Weeks 1 to 36 | Increase in Blood Pressure was defined as either: Systolic Blood Pressure (SBP) ≥ 170 mmHg and an increase from BL ≥ 20 mmHg, or as: Diastolic Blood Pressure (DBP) ≥ 100 mmHg and an increase from BL ≥ 15 mmHg. For participants who have experienced more than one event, only their first event following study treatment was used. Data reported was analyzed by Kaplan-Meier estimate for cumulative proportion and the 95% confidence interval was calculated with Greenwood's formula. |
| Change From BL in Mean Arterial Pressure (MAP) to the Average MAP Value of Weeks 20 to 28 | Baseline and weeks 20 to 28 | Baseline MAP was defined as the MAP value on day 1. If this value was missing, the latest value prior to first study drug administration was used. Mean Arterial Pressure (MAP) is derived as: MAP = (2/3)\*DBP + (1/3)\*SBP. |
| Percentage of Participants With a Hb Response During Weeks 28 and 36 Regardless of Use of Rescue Therapy | Weeks 28 to 36 | Hb response was defined as mean Hb during weeks 28 to 36 within the target range of 10.0 to 12.0 g/dL. The percentages and 95% CI are unadjusted, the exact method of Clopper-Pearson was used for 95% CI. |
| Change From BL in Hb to Each Postdosing Time Point | Baseline and weeks 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14, 16, 18,20, 22, 24, 26, 28, 30, 32, 34, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72,76, 80, 84, 88, 92, 96, 100, and 104 | Baseline Hb was defined as the mean of four latest central laboratory Hb values prior or on the same date as first study drug intake (pre-dose). |
| Hb Level Averaged Over Weeks 28 to 36, 44 to 52, and 96 to 104 Without Use of Rescue Therapy | Weeks 28 to 36, 44 to 52, and 96 to 104 | Baseline Hb was defined as the mean of four latest central laboratory Hb values prior or on the same date as first study drug intake (pre-dose). Averaged Hb values over weeks 28-36, weeks 44-52 and weeks 96-104 are observed values. |
| Change From BL in Hb to the Average of Weeks 28 to 36, 44 to 52, and 96 to 104 Regardless of the Use of Rescue Therapy | Baseline and weeks 28 to 36, 44 to 52, and 96 to 104 | Change from baseline to the average Hb are observed values. Baseline Hb was defined as the mean of four latest central laboratory Hb values prior or on the same date as first study drug intake (pre-dose). |
| Percentage of Hb Values ≥ 10 g/dL in Weeks 28 to 36, 44 to 52, and 96 to 104 Without Use of Rescue Therapy | Weeks 28-36, 44-52 and 96-104 | Percentage for each participant was calculated as Number of Hb values \>= 10.0 g/dL / Total number of Hb values\*100 in weeks 28 to 36, 44 to 52 and 96 to 104 without use of rescue therapy within 6 weeks prior to and during the 8 week evaluation period. |
| Percentage of Hb Values Within 10.0 to 12.0 g/dL in Weeks 28 to 36, 44 to 52, and 96 to 104 Without Use of Rescue Therapy | Weeks 28-36, 44-52 and 96-104 | Percentage for each participant was calculated as Number of Hb values within 10.0-12.0 g/dL / Total number of Hb values\*100 in weeks 28 to 36, 44 to 52 and 96 to 104 without use of rescue therapy within 6 weeks prior to and during the 8 week evaluation period. |
| Number of Hospitalizations | Baseline to End of Treatment (EOT) (Up to week 104) | The number of hospitalizations per participant were calculated during the Efficacy Emergent Period. The Efficacy Emergent Period was defined as the evaluation period from the Analysis date of first dose intake up to EOT Visit or last non-missing Hb assessment (for participants who died during the treatment period). It included all Non-Hemodialysis (HD) hospitalizations. The HD days were not counted as hospitalizations, even when performed overnight. |
| Number of Days of Hospitalization Per Year | Baseline to EOT (Up to week 104) | The number of days of hospitalizations per year was calculated as the sum of the durations of all non-HD hospitalizations in days (Date of discharge - Date of admission + 1)\] / (duration of efficacy emergent period in days / 365.25). In case of missing dates, the hospitalization duration was imputed by the average duration per stay derived from the participants with non-missing duration within the same treatment group. |
| Time to First Hospitalization | Baseline to EOT (Up to week 104) | Time to first hospitalization in years was defined in years as: (First event date during the Efficacy Emergent Period - Analysis date of First dose intake +1)/365.25, and the 'First event date' was defined as 'Date of first Admission and 'Analysis Date of first dose intake. For participants without hospitalization, the time to censoring was calculated as: (Date of End of Efficacy Emergent Period - Analysis Date of first dose intake + 1) / 365.25. Date of End of Efficacy Emergent Period was defined as as the treatment period up to the EOT visit. For participants who have experienced more than one hospitalization, only their first event following study treatment was used. Data reported was analyzed by Kaplan-Meier estimate for cumulative proportion and the 95% confidence interval was calculated with Greenwood's formula. |
| Time to First Use of Rescue Therapy | Baseline to EOT (Up to week 104) | Rescue therapy was defined as red blood cell (RBC) transfusion for both treatment groups and ESA for roxadustat participants. Only rescue medication that was started during the study treatment and up to end of efficacy emergent period was taken into account and considered as use of rescue medication. For participants who have experienced more than one use of rescue therapy, only their first event following study treatment was used. Data reported was analyzed by Kaplan-Meier estimate for cumulative proportion and the 95% confidence interval was calculated with Greenwood's formula. |
| Change From BL to Each Postdosing Study Visit in Apolipoproteins B (ApoB) | Baseline and weeks 8, 28, 52, 104 | Baseline was defined as the value on Day 1. If baseline value was missing, the latest value prior to first study drug administration was used regardless of fasting. |
| Time to First RBC Transfusion | Baseline to EOT (Up to week 104) | For participants who have experienced more than one RBC transfusion, only their first event following study treatment was used. For RBC transfusions, when the number of units was not given but the volume transfused was, the number of units were estimated by volume transfused/250 mL (for transfusion of packed cell units) or volume transfused/500 mL (for transfusion of full blood). Data reported was analyzed by Kaplan-Meier estimate for cumulative proportion and the 95% confidence interval was calculated with Greenwood's formula. |
| Mean Monthly Number of RBC Packs Per Participant | Baseline to EOT (Up to week 104) | During efficacy emergent period, the mean monthly number of RBC packs was calculated as the sum of blood volume and units transfused between the first dose and up to the last dose in the period divided by duration of efficacy emergent period (in days) divided by 28 days. Participants without medication records of RBC have their number of RBC packs and volume set to 0. |
| Mean Monthly Volume of RBC Transfusion Per Participant | Baseline to EOT (Up to week 104) | During Efficacy Emergent Period, the mean monthly volume of blood transfused was calculated as the sum of blood volume and units transfused between the first dose and up to the last dose in the period divided by duration of efficacy emergent period (in days) divided by 28 days. The Efficacy Emergent Period was defined as the evaluation period from the Analysis date of first dose intake up to EOT Visit or last non-missing Hb assessment (for participants who died during the treatment period). |
| Time to First Use of IV Iron Supplementation | Baseline to EOT (Up to week 104) | For participants who have received more than one IV iron, only their first event following study treatment was used. Data reported was analyzed by Kaplan-Meier estimate for cumulative proportion and the 95% confidence interval was calculated with Greenwood's formula. |
| Mean Monthly Intravenous (IV) Iron Per Participant During Weeks 37-52 and Weeks 53-104 | Weeks 37-52 and weeks 53-104 | Participants with no or missing medication records of IV Iron had their monthly IV Iron use set to 0 mg. |
| Percentage of Participants With Oral Iron Use Only | Baseline to EOT (Up to week 104) | Percentage of participants with/without IV iron only was calculated based on total number of participants within the Efficacy Emergent Period. The Efficacy Emergent Period is defined as the evaluation period from the Analysis date of first dose intake up to EOT Visit or last non-missing Hb assessment (for participants who died during the treatment period). |
| Change From BL to Each Post-dosing Study Visit in Total Cholesterol | Baseline and weeks 8, 28, 52, 104 | Baseline assessment was the assessment from Day 1 visit. If baseline value was missing, then the latest screening period value was used as the baseline regardless of fasting status. |
| Change From BL to Each Post-dosing Study Visit in LDL-C/High-density Lipoprotein Cholesterol (HDL-C) Ratio | Baseline and weeks 8, 28, 52, 104 | Baseline was defined as the value on Day 1. If baseline value was missing, the latest value prior to first study drug administration was used regardless of fasting. |
| Change From BL to Each Postdosing Study Visit in Non-HDL Cholesterol | Baseline and weeks 8, 28, 52, 104 | Baseline was defined as the value on Day 1. If baseline value was missing, the latest value prior to first study drug administration was used regardless of fasting. |
| Change From BL to Each Postdosing Study Visit in Apolipoproteins A1 (ApoA1) | Baseline and weeks 8, 28, 52, 104 | Baseline was defined as the value on Day 1. If baseline value was missing, the latest value prior to first study drug administration was used regardless of fasting. |
| Change From BL to Each Postdosing Study Visit in ApoB/ApoA1 Ratio | Baseline and weeks 8, 28, 52, 104 | Baseline was defined as the value on Day 1. If baseline value was missing, the latest value prior to first study drug administration was used. |
| Number of Participants With Mean LDL Cholesterol < 100 mg/dL Over Weeks 12 to 28 | Weeks 12 to 28 | Missing category for Fasting Only includes non-fasting participants and the participants with missing values. |
| Number of Participants With CKD Who Achieved Antihypertensive Treatment Goal | Weeks 12 to 28 | Achieved antihypertensive treatment goal was defined as SBP \< 140 mmHg and DBP \< 90 mmHg over an evaluation period based on the average of available values in weeks 12-28 (pre-dialysis). |
| Change From BL to the Average of Weeks 12 to 28 in SF-36 Physical Component Score (PCS) | Baseline and weeks 12 to 28 | Baseline SF-36 PCS was defined as the SF-36 PCS value on Day 1. SF-36 contains 36-item that measures 8 scales with scores ranging from 0-100: physical functioning (PF); role limitations due to physical health problems (RP); bodily pain (BP); social functioning (SF); general health perceptions (GH); role limitations due to emotional problems (RE); vitality, energy or fatigue (VT); and mental health (MH). These scores are normed to the US population (norm-based scoring had very little impact on results when data was collected in Western European countries) to have a mean of 50 and standard deviation of 10. The PCS was calculated based on all 8 scales and ranges from 5.02-79.78. For each of these above scales, higher scores always indicating better health status. |
| Change From BL to the Average of Weeks 12 to 28 in Anemia Subscale (AnS) (Additional Concerns) of Functional Assessment of Cancer Therapy-Anemia (FACT-An) Score | Baseline and weeks 12 to 28 | Baseline FACT-An AnS was defined as the FACT-An AnS value on Day 1. Together with the Functional Assessment of Cancer Therapy - General (FACT-G), the Anemia Subscale (AnS) is referred to as the FACT-An Total. The AnS scale contains 13 fatigue specific items (the Fatigue Score) plus 7 items related to anemia. The Anemia AnS score range is 0 to 80. For the above score, a higher score indicates better QoL. |
| Change From BL to the Average Value of Weeks 12 to 28 in Total FACT-An Score | Baseline and weeks 12 to 28 | Baseline FACT-An Total Score was defined on Day 1. Total Fact-An score is composed of FACT-G and Ans scales. FACT-G contains 27 items that cover four dimensions of well-being: physical (PWB) - 7 items, functional (FWB) - 7 items, social/family (SWB) - 7 items, and emotional (EWB) - 6 items. The AnS scale contains 13 fatigue specific items (the Fatigue Score) plus 7 items related to anemia. The total score is obtained by summation of the scores from PWB, SWB, EWB, FWB and AnS. The FACT-An Total Score scale range is 0-188. A higher score indicates better QoL. |
| Change From BL to the Average of Weeks 12 to 28 in Euroqol Questionnaire-5 Dimensions 5 Levels (EQ-5D 5L) Visual Analogue Scale (VAS) Score | Baseline and weeks 12 to 28 | Baseline assessment was defined as the value on Day 1. The EuroQol Questionnaire -5 Dimensions -5 Levels (EQ-5D-5L) is a self-reported questionnaire, used as a measure of respondents' Health Related Quality of Life (HRQoL) and utility values. The EQ-5D consists of the descriptive system and the visual analogue scale (VAS). The EQ-5D descriptive system comprises 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, extreme problems. The VAS records the respondent's self rated health status on a graduated (0-100) scale, where the endpoints are labeled 'Best imaginable health state' and 'Worst imaginable health state' with higher scores for higher HRQoL. |
| Percentage of Participants With Improvements Measured by Patients' Global Impression of Change (PGIC) | Baseline and weeks 8, 12, 28, 36, 52, 76, 104 | The PGIC is a patient-rated instrument that measures change in participant's overall status on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse), when compared to the start of treatment. The percentage of participants presented includes very much improved, much improved and minimally improved. |
| Change From BL in Serum Hepcidin | Baseline and weeks 4, 12, 20, 36, 52, 104, and End of Study (EOS - up to 108 weeks) | Baseline assessment was assessment from Day 1 visit. If baseline value was missing, the value from screening visit was used. In case of missing data, no imputation rules were applied. |
| Percentage of Participants With Hb Response During Weeks 28 to 36 | Weeks 28 to 36 | Hb response during weeks 28-36, was defined as mean Hb from 10-12 g/dL without receiving rescue therapy in the 6 weeks prior to, or during, the evaluation period. The percentages and 95% CI were unadjusted, the exact method of Clopper-Pearson was used for 95% CI. The Efficacy Emergent Period was defined as the evaluation period from the Analysis date of first dose intake up to end of treatment (EOT) Visit or last non-missing Hb assessment (for participants who died during the treatment period). |
| Change From BL in Transferrin Saturation (TSAT) | Baseline and weeks 4, 8, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 104 and EOS (up to 108 weeks) | Baseline assessment was assessment from Day 1 visit. If baseline value was missing, the value from screening visit was used. In case of missing data, no imputation rules were applied. |
| Change From BL in Glycated Hemoglobin (HbA1c) Level to Weeks 12, 28, 36, 44, 52, 60, 84, 104 and EOS (up to Week 108) | Baseline and weeks 12, 28, 36, 44, 52, 60, 84, 104 and EOS (up to 108 weeks) | Percentage of change from baseline to each study visit were calculated for HbA1c. Baseline assessment was assessment from Day 1 visit. If baseline value was missing, the value from screening visit was used. In case of missing data, no imputation rules were applied. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Baseline up to EOS (Up to week 108) | Safety was assessed by evaluation of the following variables: (TEAEs; frequency, severity, seriousness, and relationship to study drug), Vital signs (systolic and diastolic blood pressure, pulse, respiratory rate and weight), Clinical laboratory variables (hematology, biochemistry including liver enzymes and total bilirubin, and urinalysis), Physical examination, 12-lead electrocardiogram (ECG) and Vascular Access Thrombosis. All AEs collected during the Safety Emergent Period were counted as TEAE. The TEAE was defined as an adverse event (AE) if it was observed after starting administration of the roxadustat or ESA. Any clinically significant abnormalities were reported as an AEs. All reported deaths after the first study drug administration and up to 28 days after the Analysis Date of Last Dose and considering last dosing frequency. |
| Change From BL in Serum Ferritin | Baseline and weeks 4, 8, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 104, and EOS (up to 108 weeks) | Baseline assessment was assessment from Day 1 visit. If baseline value was missing, the value from screening visit was used. In case of missing data, no imputation rules were applied. |
| Change From BL in Low Density Lipoprotein Cholesterol (LDL-C) to the Average LDL-C of Weeks 12 to 28 | Baseline and weeks 12 to 28 | Baseline LDL was defined as the LDL value on Day 1. If this value was missing, the latest value prior to first study drug administration was used. |
Countries
Belgium, Bulgaria, Croatia, Czechia, France, Georgia, Germany, Hungary, Italy, Poland, Portugal, Romania, Russia, Serbia, Slovakia, Spain, United Kingdom
Participant flow
Recruitment details
Study population consisted of participants with end-stage renal disease (ESRD) who were on stable hemodialysis (HD) or peritoneal dialysis (PD), and were also on stable treatment with epoetin (i.e. epoetin alfa, beta, theta, zeta, delta or omega) or darbepoetin alfa for anemia.
Pre-assignment details
Participants were randomized in a 1:1 ratio to roxadustat or ESA (epoetin alfa or darbepoetin alfa). Randomization was stratified by 5 factors: previous ESA treatment, region, history of cardiovascular, cerebrovascular or thromboembolic diseases, average weekly ESA dose 4 weeks prior to randomization and the screening hemaglobin (Hb) value.
Participants by arm
| Arm | Count |
|---|---|
| Roxadustat Participants received roxadustat three times a week (TIW) for at least 52 weeks up to a maximum of 104 weeks. Participants received initial dose of roxadustat in doses of 100 mg, 150 mg or 200 mg, according to the average weekly dose of epoetin or darbepoetin alfa prior to randomization. Participants' roxadustat dosage was adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps were as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300, and 400 mg. Oral iron treatment of 200 mg was allowed for supplementation to support erythropoiesis. Treatment with intravenous iron was allowed only if certain protocol criteria were met. | 415 |
| ESA (Erythropoiesis-Stimulating Agent) Participants received epoetin alfa once weekly, twice weekly or TIW and darbepoetin alfa once a week or once every other week. Participants were treated for at least 52 weeks up to a maximum of 104 weeks. Treatment dosage was adjusted according to the pre-specified rule of keeping the participant's Hb levels between 10.0 to 12.0 g/dL. Participants were not allowed to switch from epoetin alfa to darbepoetin alfa or vice versa. | 421 |
| Total | 836 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 0 |
| Overall Study | Death | 68 | 56 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Miscellaneous | 15 | 14 |
| Overall Study | Physician Decision | 1 | 1 |
| Overall Study | Randomized but never received study drug | 1 | 1 |
| Overall Study | Withdrawal by Subject | 30 | 19 |
Baseline characteristics
| Characteristic | Total | Roxadustat | ESA (Erythropoiesis-Stimulating Agent) |
|---|---|---|---|
| Age, Continuous | 61.4 Years STANDARD_DEVIATION 13.6 | 61 Years STANDARD_DEVIATION 13.8 | 61.8 Years STANDARD_DEVIATION 13.4 |
| Baseline Hemoglobin (Hb) Value <=11.0 g/dL | 533 Participants | 267 Participants | 266 Participants |
| Baseline Hemoglobin (Hb) Value >11.0 g/dL | 303 Participants | 148 Participants | 155 Participants |
| Baseline Mean Hb | 10.76 g/dL STANDARD_DEVIATION 0.62 | 10.75 g/dL STANDARD_DEVIATION 0.62 | 10.77 g/dL STANDARD_DEVIATION 0.62 |
| Race/Ethnicity, Customized ASIAN | 5 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized BLACK OR AFRICAN AMERICAN | 12 Participants | 6 Participants | 6 Participants |
| Race/Ethnicity, Customized OTHER | 6 Participants | 2 Participants | 4 Participants |
| Race/Ethnicity, Customized WHITE | 813 Participants | 405 Participants | 408 Participants |
| Sex: Female, Male Female | 354 Participants | 169 Participants | 185 Participants |
| Sex: Female, Male Male | 482 Participants | 246 Participants | 236 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 78 / 414 | 59 / 420 |
| other Total, other adverse events | 210 / 414 | 209 / 420 |
| serious Total, serious adverse events | 210 / 414 | 189 / 420 |
Outcome results
Primary
Change From Baseline (BL) to the Average Hemoglobin (Hb) in Weeks 28-36 Without Rescue Therapy [EU (EMA)]
Baseline Hb was defined as the mean of four central laboratory Hb values; four latest Hb values prior or on the same date as the first study drug intake. For participants who did not have an available Hb value during the week 28-36 period, imputation rules were applied. For analyses without rescue therapy, participants who used rescue therapy after the initiation of rescue therapy were set to missing for 6 weeks from the start date of rescue therapy. If no Hb value was available, an imputation technique was used, with the mean of all available values from Day 1 to minimum (End of Efficacy Emergent Period) carried forward.
Time frame: Baseline and weeks 28 to 36
Population: The analysis population was the Per Protocol Set (PPS) which consisted of all Full Analysis Set (FAS) participants who did not meet any of exclusion criteria from the PPS. The FAS consisted of all randomized participants who received at least one dose of study drug and had at least one post-dose valid Hb assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Roxadustat | Change From Baseline (BL) to the Average Hemoglobin (Hb) in Weeks 28-36 Without Rescue Therapy [EU (EMA)] | 0.428 g/dL |
| ESA (Erythropoiesis-Stimulating Agent) | Change From Baseline (BL) to the Average Hemoglobin (Hb) in Weeks 28-36 Without Rescue Therapy [EU (EMA)] | 0.193 g/dL |
Comparison: The model includes treatment arm, region, CV History, previous ESA treatment, visits and visit by treatment as categorical variables and baseline Hb and baseline Hb by visit as continuous variable.p-value: <0.00195% CI: [0.132, 0.339]Mixed Models Analysis
Primary
Change From BL to the Average Hb in Weeks 28 to 52 Regardless of Rescue Therapy [US (FDA)]
Baseline Hb was defined as the mean of four central laboratory Hb values: four latest Hb values prior or on the same date as first study drug intake. Change from baseline to the average Hb are observed values. Missing hemoglobin 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 with treatment, baseline hemoglobin, randomization stratification factors and the available non missing hemoglobin for each scheduled week.
Time frame: Baseline and weeks 28 to 52
Population: The analysis population was the All Randomized, which consisted of participants who received at least one dose of study drug, and who had available data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Roxadustat | Change From BL to the Average Hb in Weeks 28 to 52 Regardless of Rescue Therapy [US (FDA)] | 0.363 g/dL |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL to the Average Hb in Weeks 28 to 52 Regardless of Rescue Therapy [US (FDA)] | 0.192 g/dL |
Comparison: The model includes treatment arm, region, CV History, previous ESA treatment as categorical variables and baseline Hb as continuous variable. Statistical analysis used was ANCOVA model with multiple imputations (MI). Missing hemoglobin data was imputed for each treatment relying on non-missing data from all participants within each treatment group using the MCMC imputation model.p-value: <0.00195% CI: [0.082, 0.261]ANCOVA
Secondary
Change From BL in Glycated Hemoglobin (HbA1c) Level to Weeks 12, 28, 36, 44, 52, 60, 84, 104 and EOS (up to Week 108)
Percentage of change from baseline to each study visit were calculated for HbA1c. Baseline assessment was assessment from Day 1 visit. If baseline value was missing, the value from screening visit was used. In case of missing data, no imputation rules were applied.
Time frame: Baseline and weeks 12, 28, 36, 44, 52, 60, 84, 104 and EOS (up to 108 weeks)
Population: The analysis population was the FAS, with participants who had available data at baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Roxadustat | Change From BL in Glycated Hemoglobin (HbA1c) Level to Weeks 12, 28, 36, 44, 52, 60, 84, 104 and EOS (up to Week 108) | Week 28 | -0.0004 percentage of Glycated Hemoglobin | Standard Deviation 0.0067 |
| Roxadustat | Change From BL in Glycated Hemoglobin (HbA1c) Level to Weeks 12, 28, 36, 44, 52, 60, 84, 104 and EOS (up to Week 108) | Week 60 | 0.0000 percentage of Glycated Hemoglobin | Standard Deviation 0.008 |
| Roxadustat | Change From BL in Glycated Hemoglobin (HbA1c) Level to Weeks 12, 28, 36, 44, 52, 60, 84, 104 and EOS (up to Week 108) | Week 44 | -0.0001 percentage of Glycated Hemoglobin | Standard Deviation 0.0069 |
| Roxadustat | Change From BL in Glycated Hemoglobin (HbA1c) Level to Weeks 12, 28, 36, 44, 52, 60, 84, 104 and EOS (up to Week 108) | Week 84 | 0.0003 percentage of Glycated Hemoglobin | Standard Deviation 0.0072 |
| Roxadustat | Change From BL in Glycated Hemoglobin (HbA1c) Level to Weeks 12, 28, 36, 44, 52, 60, 84, 104 and EOS (up to Week 108) | Week 36 | -0.0001 percentage of Glycated Hemoglobin | Standard Deviation 0.0065 |
| Roxadustat | Change From BL in Glycated Hemoglobin (HbA1c) Level to Weeks 12, 28, 36, 44, 52, 60, 84, 104 and EOS (up to Week 108) | Week 104 | 0.0000 percentage of Glycated Hemoglobin | Standard Deviation 0.0075 |
| Roxadustat | Change From BL in Glycated Hemoglobin (HbA1c) Level to Weeks 12, 28, 36, 44, 52, 60, 84, 104 and EOS (up to Week 108) | Week 52 | -0.0001 percentage of Glycated Hemoglobin | Standard Deviation 0.007 |
| Roxadustat | Change From BL in Glycated Hemoglobin (HbA1c) Level to Weeks 12, 28, 36, 44, 52, 60, 84, 104 and EOS (up to Week 108) | EOS | 0.0011 percentage of Glycated Hemoglobin | Standard Deviation 0.0076 |
| Roxadustat | Change From BL in Glycated Hemoglobin (HbA1c) Level to Weeks 12, 28, 36, 44, 52, 60, 84, 104 and EOS (up to Week 108) | Week 12 | 0.0009 percentage of Glycated Hemoglobin | Standard Deviation 0.0071 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Glycated Hemoglobin (HbA1c) Level to Weeks 12, 28, 36, 44, 52, 60, 84, 104 and EOS (up to Week 108) | EOS | 0.0001 percentage of Glycated Hemoglobin | Standard Deviation 0.008 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Glycated Hemoglobin (HbA1c) Level to Weeks 12, 28, 36, 44, 52, 60, 84, 104 and EOS (up to Week 108) | Week 12 | -0.0005 percentage of Glycated Hemoglobin | Standard Deviation 0.0057 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Glycated Hemoglobin (HbA1c) Level to Weeks 12, 28, 36, 44, 52, 60, 84, 104 and EOS (up to Week 108) | Week 28 | -0.0006 percentage of Glycated Hemoglobin | Standard Deviation 0.0064 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Glycated Hemoglobin (HbA1c) Level to Weeks 12, 28, 36, 44, 52, 60, 84, 104 and EOS (up to Week 108) | Week 36 | -0.0004 percentage of Glycated Hemoglobin | Standard Deviation 0.0067 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Glycated Hemoglobin (HbA1c) Level to Weeks 12, 28, 36, 44, 52, 60, 84, 104 and EOS (up to Week 108) | Week 44 | -0.0006 percentage of Glycated Hemoglobin | Standard Deviation 0.0067 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Glycated Hemoglobin (HbA1c) Level to Weeks 12, 28, 36, 44, 52, 60, 84, 104 and EOS (up to Week 108) | Week 52 | -0.0007 percentage of Glycated Hemoglobin | Standard Deviation 0.0068 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Glycated Hemoglobin (HbA1c) Level to Weeks 12, 28, 36, 44, 52, 60, 84, 104 and EOS (up to Week 108) | Week 60 | -0.0004 percentage of Glycated Hemoglobin | Standard Deviation 0.007 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Glycated Hemoglobin (HbA1c) Level to Weeks 12, 28, 36, 44, 52, 60, 84, 104 and EOS (up to Week 108) | Week 84 | 0.0001 percentage of Glycated Hemoglobin | Standard Deviation 0.0078 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Glycated Hemoglobin (HbA1c) Level to Weeks 12, 28, 36, 44, 52, 60, 84, 104 and EOS (up to Week 108) | Week 104 | -0.0003 percentage of Glycated Hemoglobin | Standard Deviation 0.0082 |
Secondary
Change From BL in Hb to Each Postdosing Time Point
Baseline Hb was defined as the mean of four latest central laboratory Hb values prior or on the same date as first study drug intake (pre-dose).
Time frame: Baseline and weeks 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14, 16, 18,20, 22, 24, 26, 28, 30, 32, 34, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72,76, 80, 84, 88, 92, 96, 100, and 104
Population: The analysis population was the FAS.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Roxadustat | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 1 | 0.232 g/dL |
| Roxadustat | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 2 | 0.496 g/dL |
| Roxadustat | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 3 | 0.633 g/dL |
| Roxadustat | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 4 | 0.803 g/dL |
| Roxadustat | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 5 | 0.723 g/dL |
| Roxadustat | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 6 | 0.868 g/dL |
| Roxadustat | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 7 | 0.698 g/dL |
| Roxadustat | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 8 | 0.816 g/dL |
| Roxadustat | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 10 | 0.640 g/dL |
| Roxadustat | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 12 | 0.732 g/dL |
| Roxadustat | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 14 | 0.508 g/dL |
| Roxadustat | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 16 | 0.613 g/dL |
| Roxadustat | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 18 | 0.380 g/dL |
| Roxadustat | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 20 | 0.501 g/dL |
| Roxadustat | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 22 | 0.266 g/dL |
| Roxadustat | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 24 | 0.262 g/dL |
| Roxadustat | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 26 | 0.316 g/dL |
| Roxadustat | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 28 | 0.549 g/dL |
| Roxadustat | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 30 | 0.333 g/dL |
| Roxadustat | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 32 | 0.310 g/dL |
| Roxadustat | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 34 | 0.364 g/dL |
| Roxadustat | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 36 | 0.482 g/dL |
| Roxadustat | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 40 | 0.199 g/dL |
| Roxadustat | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 44 | 0.335 g/dL |
| Roxadustat | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 48 | 0.158 g/dL |
| Roxadustat | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 52 | 0.385 g/dL |
| Roxadustat | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 56 | 0.217 g/dL |
| Roxadustat | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 60 | 0.368 g/dL |
| Roxadustat | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 64 | 0.181 g/dL |
| Roxadustat | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 68 | 0.306 g/dL |
| Roxadustat | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 72 | 0.109 g/dL |
| Roxadustat | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 76 | 0.401 g/dL |
| Roxadustat | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 80 | 0.087 g/dL |
| Roxadustat | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 84 | 0.318 g/dL |
| Roxadustat | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 88 | 0.026 g/dL |
| Roxadustat | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 92 | 0.357 g/dL |
| Roxadustat | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 96 | 0.126 g/dL |
| Roxadustat | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 100 | 0.302 g/dL |
| Roxadustat | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 104 | 0.232 g/dL |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 32 | 0.111 g/dL |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 1 | 0.068 g/dL |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 68 | 0.100 g/dL |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 2 | 0.054 g/dL |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 34 | 0.084 g/dL |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 3 | 0.071 g/dL |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 88 | -0.018 g/dL |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 4 | 0.095 g/dL |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 36 | 0.225 g/dL |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 5 | -0.045 g/dL |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 72 | -0.009 g/dL |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 6 | 0.138 g/dL |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 40 | 0.064 g/dL |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 7 | -0.031 g/dL |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 104 | 0.133 g/dL |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 8 | 0.116 g/dL |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 44 | 0.252 g/dL |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 10 | -0.019 g/dL |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 76 | 0.189 g/dL |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 12 | 0.139 g/dL |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 48 | 0.131 g/dL |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 14 | 0.005 g/dL |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 92 | 0.154 g/dL |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 16 | 0.244 g/dL |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 52 | 0.186 g/dL |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 18 | 0.017 g/dL |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 80 | -0.015 g/dL |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 20 | 0.217 g/dL |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 56 | 0.069 g/dL |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 22 | 0.069 g/dL |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 100 | 0.138 g/dL |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 24 | 0.075 g/dL |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 60 | 0.171 g/dL |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 26 | 0.073 g/dL |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 84 | 0.126 g/dL |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 28 | 0.342 g/dL |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 64 | -0.093 g/dL |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 30 | 0.106 g/dL |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Hb to Each Postdosing Time Point | Hb Change From BL to Week 96 | -0.058 g/dL |
Comparison: Week 1- The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.p-value: <0.00195% CI: [0.072, 0.256]Mixed Models Analysis
Comparison: Week 2- The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.p-value: <0.00195% CI: [0.339, 0.546]Mixed Models Analysis
Comparison: Week 3 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.p-value: <0.00195% CI: [0.451, 0.672]Mixed Models Analysis
Comparison: Week 4 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.p-value: <0.00195% CI: [0.588, 0.828]Mixed Models Analysis
Comparison: Week 5 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.p-value: <0.00195% CI: [0.645, 0.89]Mixed Models Analysis
Comparison: Week 6 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.p-value: <0.00195% CI: [0.604, 0.855]Mixed Models Analysis
Comparison: Week 7 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.p-value: <0.00195% CI: [0.603, 0.856]Mixed Models Analysis
Comparison: Week 8 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.p-value: <0.00195% CI: [0.574, 0.826]Mixed Models Analysis
Comparison: Week 10 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.p-value: <0.00195% CI: [0.53, 0.788]Mixed Models Analysis
Comparison: Week 12 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.p-value: <0.00195% CI: [0.459, 0.727]Mixed Models Analysis
Comparison: Week 14 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.p-value: <0.00195% CI: [0.366, 0.64]Mixed Models Analysis
Comparison: Week 16 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.p-value: <0.00195% CI: [0.229, 0.51]Mixed Models Analysis
Comparison: Week 18 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.p-value: <0.00195% CI: [0.23, 0.496]Mixed Models Analysis
Comparison: Week 20 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.p-value: <0.00195% CI: [0.154, 0.414]Mixed Models Analysis
Comparison: Week 22 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.p-value: =0.00395% CI: [0.065, 0.329]Mixed Models Analysis
Comparison: Week 24 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.p-value: =0.00495% CI: [0.059, 0.316]Mixed Models Analysis
Comparison: Week 26 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.p-value: <0.00195% CI: [0.113, 0.373]Mixed Models Analysis
Comparison: Week 28 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.p-value: =0.00295% CI: [0.074, 0.34]Mixed Models Analysis
Comparison: Week 30 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.p-value: <0.00195% CI: [0.096, 0.358]Mixed Models Analysis
Comparison: Week 32 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.p-value: =0.00495% CI: [0.064, 0.334]Mixed Models Analysis
Comparison: Week 34 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.p-value: <0.00195% CI: [0.15, 0.409]Mixed Models Analysis
Comparison: Week 36- The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.p-value: <0.00195% CI: [0.121, 0.391]Mixed Models Analysis
Comparison: Week 40 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.p-value: =0.0695% CI: [-0.006, 0.277]Mixed Models Analysis
Comparison: Week 44 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.p-value: =0.29395% CI: [-0.071, 0.236]Mixed Models Analysis
Comparison: Week 48 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.p-value: =0.72395% CI: [-0.123, 0.177]Mixed Models Analysis
Comparison: Week 52 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.p-value: =0.00995% CI: [0.049, 0.348]Mixed Models Analysis
Comparison: Week 56 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.p-value: =0.05695% CI: [-0.004, 0.298]Mixed Models Analysis
Comparison: Week 60 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.p-value: =0.0195% CI: [0.047, 0.346]Mixed Models Analysis
Comparison: Week 64 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.p-value: <0.00195% CI: [0.123, 0.427]Mixed Models Analysis
Comparison: Week 68 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.p-value: =0.00695% CI: [0.059, 0.353]Mixed Models Analysis
Comparison: Week 72 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.p-value: =0.12795% CI: [-0.033, 0.269]Mixed Models Analysis
Comparison: Week 76 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.p-value: =0.0195% CI: [0.051, 0.371]Mixed Models Analysis
Comparison: Week 80 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.p-value: =0.19195% CI: [-0.051, 0.255]Mixed Models Analysis
Comparison: Week 84 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.p-value: =0.01895% CI: [0.033, 0.351]Mixed Models Analysis
Comparison: Week 88 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.p-value: =0.57695% CI: [-0.111, 0.2]Mixed Models Analysis
Comparison: Week 92 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.p-value: =0.01795% CI: [0.037, 0.369]Mixed Models Analysis
Comparison: Week 96 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.p-value: =0.01995% CI: [0.031, 0.338]Mixed Models Analysis
Comparison: Week 100 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.p-value: =0.05695% CI: [-0.004, 0.333]Mixed Models Analysis
Comparison: Week 104 - The model included treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline Hb as continuous covariates.p-value: =0.26795% CI: [-0.076, 0.273]Mixed Models Analysis
Secondary
Change From BL in Hb to the Average of Weeks 28 to 36, 44 to 52, and 96 to 104 Regardless of the Use of Rescue Therapy
Change from baseline to the average Hb are observed values. Baseline Hb was defined as the mean of four latest central laboratory Hb values prior or on the same date as first study drug intake (pre-dose).
Time frame: Baseline and weeks 28 to 36, 44 to 52, and 96 to 104
Population: The analysis population was the FAS.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Roxadustat | Change From BL in Hb to the Average of Weeks 28 to 36, 44 to 52, and 96 to 104 Regardless of the Use of Rescue Therapy | Hb Change From BL to Weeks 28-36 | 0.408 g/dL |
| Roxadustat | Change From BL in Hb to the Average of Weeks 28 to 36, 44 to 52, and 96 to 104 Regardless of the Use of Rescue Therapy | Hb Change From BL to Weeks 44-52 | 0.298 g/dL |
| Roxadustat | Change From BL in Hb to the Average of Weeks 28 to 36, 44 to 52, and 96 to 104 Regardless of the Use of Rescue Therapy | Hb Change From BL to Weeks 96-104 | 0.225 g/dL |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Hb to the Average of Weeks 28 to 36, 44 to 52, and 96 to 104 Regardless of the Use of Rescue Therapy | Hb Change From BL to Weeks 28-36 | 0.173 g/dL |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Hb to the Average of Weeks 28 to 36, 44 to 52, and 96 to 104 Regardless of the Use of Rescue Therapy | Hb Change From BL to Weeks 44-52 | 0.194 g/dL |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Hb to the Average of Weeks 28 to 36, 44 to 52, and 96 to 104 Regardless of the Use of Rescue Therapy | Hb Change From BL to Weeks 96-104 | 0.076 g/dL |
Comparison: Weeks 28-36 - The model includes treatment arm, region, CV History, previous ESA treatment, visits and visit by treatment as categorical variables and baseline Hb as continuous variable.p-value: <0.00195% CI: [0.125, 0.346]Mixed Models Analysis
Comparison: Weeks 44-52 - The model includes treatment arm, region, CV History, previous ESA treatment, visits and visit by treatment as categorical variables and baseline Hb as continuous variable.p-value: =0.1195% CI: [-0.024, 0.232]Mixed Models Analysis
Comparison: Weeks 96-104 - The model includes treatment arm, region, CV History, previous ESA treatment, visits and visit by treatment as categorical variables and baseline Hb as continuous variable.p-value: =0.03695% CI: [0.01, 0.288]Mixed Models Analysis
Secondary
Change From BL in Low Density Lipoprotein Cholesterol (LDL-C) to the Average LDL-C of Weeks 12 to 28
Baseline LDL was defined as the LDL value on Day 1. If this value was missing, the latest value prior to first study drug administration was used.
Time frame: Baseline and weeks 12 to 28
Population: The analysis population was the FAS, with participants who had available data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Roxadustat | Change From BL in Low Density Lipoprotein Cholesterol (LDL-C) to the Average LDL-C of Weeks 12 to 28 | -0.459 mmol/L |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Low Density Lipoprotein Cholesterol (LDL-C) to the Average LDL-C of Weeks 12 to 28 | -0.082 mmol/L |
Comparison: The model includes treatment arm, region, CV History, previous ESA treatment, visits and visit by treatment as categorical variables and baseline LDL, baseline Hb as continuous variables.p-value: <0.00195% CI: [-0.451, -0.304]Mixed Models Analysis
Secondary
Change From BL in Mean Arterial Pressure (MAP) to the Average MAP Value of Weeks 20 to 28
Baseline MAP was defined as the MAP value on day 1. If this value was missing, the latest value prior to first study drug administration was used. Mean Arterial Pressure (MAP) is derived as: MAP = (2/3)\*DBP + (1/3)\*SBP.
Time frame: Baseline and weeks 20 to 28
Population: The analysis population was the FAS, with participants who had available data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Roxadustat | Change From BL in Mean Arterial Pressure (MAP) to the Average MAP Value of Weeks 20 to 28 | -0.739 mmHg |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Mean Arterial Pressure (MAP) to the Average MAP Value of Weeks 20 to 28 | -0.160 mmHg |
Comparison: The model includes treatment arm, region, CV History, previous ESA treatment, visits and visit by treatment as categorical variables, and baseline MAP, baseline Hb as continuous variables.p-value: =0.30895% CI: [-1.694, 0.536]Mixed Models Analysis
Secondary
Change From BL in Mean Arterial Pressure (MAP) to the Average of Weeks 20 to 28
Baseline MAP was defined as the MAP value on Day 1. If this value was missing, the latest value prior to first study drug administration was used. Mean Arterial Pressure (MAP) is derived as: MAP = (2/3)\*DBP + (1/3)\*SBP.
Time frame: Baseline and weeks 20 to 28
Population: The analysis population was the PPS, with participants who had available data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Roxadustat | Change From BL in Mean Arterial Pressure (MAP) to the Average of Weeks 20 to 28 | -0.969 mmHg |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Mean Arterial Pressure (MAP) to the Average of Weeks 20 to 28 | -0.120 mmHg |
Comparison: The model includes treatment arm, region, CV History, previous ESA treatment, visits and visit by treatment as categorical variables, and baseline MAP, baseline Hb as continuous variables.p-value: <0.0595% CI: [-1.971, 0.273]Mixed Models Analysis
Secondary
Change From BL in Serum Ferritin
Baseline assessment was assessment from Day 1 visit. If baseline value was missing, the value from screening visit was used. In case of missing data, no imputation rules were applied.
Time frame: Baseline and weeks 4, 8, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 104, and EOS (up to 108 weeks)
Population: The analysis population was the FAS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Roxadustat | Change From BL in Serum Ferritin | Week 4 | -214.64 pmol/L | Standard Deviation 824.96 |
| Roxadustat | Change From BL in Serum Ferritin | Week 8 | -245.37 pmol/L | Standard Deviation 668.51 |
| Roxadustat | Change From BL in Serum Ferritin | Week 12 | -269.76 pmol/L | Standard Deviation 761.24 |
| Roxadustat | Change From BL in Serum Ferritin | Week 20 | -337.94 pmol/L | Standard Deviation 645.73 |
| Roxadustat | Change From BL in Serum Ferritin | Week 28 | -427.46 pmol/L | Standard Deviation 699.95 |
| Roxadustat | Change From BL in Serum Ferritin | Week 36 | -507.34 pmol/L | Standard Deviation 726.61 |
| Roxadustat | Change From BL in Serum Ferritin | Week 44 | -545.14 pmol/L | Standard Deviation 668.02 |
| Roxadustat | Change From BL in Serum Ferritin | Week 52 | -615.19 pmol/L | Standard Deviation 677.97 |
| Roxadustat | Change From BL in Serum Ferritin | Week 60 | -622.55 pmol/L | Standard Deviation 675.22 |
| Roxadustat | Change From BL in Serum Ferritin | Week 68 | -604.47 pmol/L | Standard Deviation 773.19 |
| Roxadustat | Change From BL in Serum Ferritin | Week 76 | -646.76 pmol/L | Standard Deviation 838.76 |
| Roxadustat | Change From BL in Serum Ferritin | Week 84 | -629.31 pmol/L | Standard Deviation 1060.24 |
| Roxadustat | Change From BL in Serum Ferritin | Week 92 | -749.58 pmol/L | Standard Deviation 828.32 |
| Roxadustat | Change From BL in Serum Ferritin | Week 100 | -746.86 pmol/L | Standard Deviation 796.74 |
| Roxadustat | Change From BL in Serum Ferritin | Week 104 | -753.82 pmol/L | Standard Deviation 791.12 |
| Roxadustat | Change From BL in Serum Ferritin | EOS | -554.53 pmol/L | Standard Deviation 910.01 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Serum Ferritin | EOS | -166.94 pmol/L | Standard Deviation 2035.26 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Serum Ferritin | Week 4 | -141.78 pmol/L | Standard Deviation 456.15 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Serum Ferritin | Week 60 | -394.40 pmol/L | Standard Deviation 837.81 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Serum Ferritin | Week 8 | -160.75 pmol/L | Standard Deviation 607.39 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Serum Ferritin | Week 92 | -371.64 pmol/L | Standard Deviation 1157.18 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Serum Ferritin | Week 12 | -179.47 pmol/L | Standard Deviation 586.95 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Serum Ferritin | Week 68 | -456.16 pmol/L | Standard Deviation 1039.18 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Serum Ferritin | Week 20 | -246.89 pmol/L | Standard Deviation 727.64 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Serum Ferritin | Week 104 | -348.70 pmol/L | Standard Deviation 1292.49 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Serum Ferritin | Week 28 | -265.21 pmol/L | Standard Deviation 816.64 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Serum Ferritin | Week 76 | -447.70 pmol/L | Standard Deviation 967.63 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Serum Ferritin | Week 36 | -269.26 pmol/L | Standard Deviation 855.01 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Serum Ferritin | Week 100 | -364.78 pmol/L | Standard Deviation 1802.37 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Serum Ferritin | Week 44 | -323.30 pmol/L | Standard Deviation 986.38 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Serum Ferritin | Week 84 | -454.44 pmol/L | Standard Deviation 1193.43 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Serum Ferritin | Week 52 | -347.58 pmol/L | Standard Deviation 1058.87 |
Secondary
Change From BL in Serum Hepcidin
Baseline assessment was assessment from Day 1 visit. If baseline value was missing, the value from screening visit was used. In case of missing data, no imputation rules were applied.
Time frame: Baseline and weeks 4, 12, 20, 36, 52, 104, and End of Study (EOS - up to 108 weeks)
Population: The analysis population was the FAS, with participants who had available data at baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Roxadustat | Change From BL in Serum Hepcidin | Week 20 | -15.149 µg/L | Standard Deviation 43.152 |
| Roxadustat | Change From BL in Serum Hepcidin | Week 52 | -32.709 µg/L | Standard Deviation 42.342 |
| Roxadustat | Change From BL in Serum Hepcidin | Week 12 | -12.298 µg/L | Standard Deviation 41.335 |
| Roxadustat | Change From BL in Serum Hepcidin | Week 104 | -40.101 µg/L | Standard Deviation 48.611 |
| Roxadustat | Change From BL in Serum Hepcidin | Week 36 | -23.405 µg/L | Standard Deviation 43.033 |
| Roxadustat | Change From BL in Serum Hepcidin | EOS | -27.192 µg/L | Standard Deviation 52.169 |
| Roxadustat | Change From BL in Serum Hepcidin | Week 4 | -14.265 µg/L | Standard Deviation 42.393 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Serum Hepcidin | EOS | -17.664 µg/L | Standard Deviation 51.688 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Serum Hepcidin | Week 4 | -4.265 µg/L | Standard Deviation 33.518 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Serum Hepcidin | Week 12 | -6.741 µg/L | Standard Deviation 38.507 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Serum Hepcidin | Week 20 | -11.818 µg/L | Standard Deviation 41.596 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Serum Hepcidin | Week 36 | -14.530 µg/L | Standard Deviation 43.449 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Serum Hepcidin | Week 52 | -17.522 µg/L | Standard Deviation 47.307 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Serum Hepcidin | Week 104 | -18.735 µg/L | Standard Deviation 51.632 |
Secondary
Change From BL in SF-36 Vitality (VT) Sub-score to the Average of Weeks 12 to 28
Baseline VT Subscore was defined as the VT value on Day 1. The SF-36 is a QoL instrument designed to assess generic health concepts relevant across age, disease, and treatment groups. The SF-36 vitality has four questions with score range from 0-100 with higher scores indicating better vitality status.
Time frame: Baseline and weeks 12 to 28
Population: The analysis population was the PPS, with participants who had available data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Roxadustat | Change From BL in SF-36 Vitality (VT) Sub-score to the Average of Weeks 12 to 28 | 0.460 Units on a scale |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in SF-36 Vitality (VT) Sub-score to the Average of Weeks 12 to 28 | -0.396 Units on a scale |
Comparison: The model includes treatment arm, region, CV History, previous ESA treatment, visits (week 8, week 12, week 28) and visit by treatment as categorical variables, and baseline SF-36 VT, baseline Hb as continuous variables.p-value: <0.0595% CI: [-0.115, 1.828]Mixed Models Analysis
Secondary
Change From BL in Short Form-36 (SF-36) Health Survey Physical Functioning (PF) Sub-score to the Average of Weeks 12 to 28
Baseline SF-36 PF was defined as the SF-36 PF value on Day 1.The SF-36 is a Quality of Life (QoL) instrument designed to assess generic health concepts relevant across age, disease, and treatment groups. The SF-36 contains 36 items that measure eight scales: (1) physical functioning (PF); (2) role limitations due to physical health problems (RP); (3) bodily pain (BP); (4) social functioning (SF); (5) general health perceptions (GH); (6) role limitations due to emotional problems (RE); (7) vitality, energy or fatigue (VT); and (8) mental health(MH). Each scale is transformed into 0-100 score, with higher scores indicating better health status. The SF-36 PF consists of 11 questions focused on health and ability to do usual activities, with higher scores indicating better health status.
Time frame: Baseline and weeks 12 to 28
Population: The analysis population was the PPS, with participants who had available data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Roxadustat | Change From BL in Short Form-36 (SF-36) Health Survey Physical Functioning (PF) Sub-score to the Average of Weeks 12 to 28 | 0.050 Units on a scale |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Short Form-36 (SF-36) Health Survey Physical Functioning (PF) Sub-score to the Average of Weeks 12 to 28 | -0.155 Units on a scale |
Comparison: The model includes treatment arm, region, CV History, previous ESA treatment, visits (week 8, week 12, week 28) and visit by treatment as categorical variables, and baseline SF-36 PF, baseline Hb as continuous variables.p-value: <0.0595% CI: [-0.649, 1.059]Mixed Models Analysis
Secondary
Change From BL in Transferrin Saturation (TSAT)
Baseline assessment was assessment from Day 1 visit. If baseline value was missing, the value from screening visit was used. In case of missing data, no imputation rules were applied.
Time frame: Baseline and weeks 4, 8, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 104 and EOS (up to 108 weeks)
Population: The analysis population was the FAS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Roxadustat | Change From BL in Transferrin Saturation (TSAT) | Week 4 | -4.151 Percentage of saturation | Standard Deviation 16.147 |
| Roxadustat | Change From BL in Transferrin Saturation (TSAT) | Week 8 | -3.681 Percentage of saturation | Standard Deviation 17.062 |
| Roxadustat | Change From BL in Transferrin Saturation (TSAT) | Week 12 | -2.643 Percentage of saturation | Standard Deviation 17.551 |
| Roxadustat | Change From BL in Transferrin Saturation (TSAT) | Week 20 | -3.782 Percentage of saturation | Standard Deviation 16.634 |
| Roxadustat | Change From BL in Transferrin Saturation (TSAT) | Week 28 | -5.463 Percentage of saturation | Standard Deviation 17.798 |
| Roxadustat | Change From BL in Transferrin Saturation (TSAT) | Week 36 | -5.351 Percentage of saturation | Standard Deviation 17.803 |
| Roxadustat | Change From BL in Transferrin Saturation (TSAT) | Week 44 | -6.069 Percentage of saturation | Standard Deviation 16.349 |
| Roxadustat | Change From BL in Transferrin Saturation (TSAT) | Week 52 | -7.278 Percentage of saturation | Standard Deviation 17.244 |
| Roxadustat | Change From BL in Transferrin Saturation (TSAT) | Week 60 | -6.997 Percentage of saturation | Standard Deviation 16.774 |
| Roxadustat | Change From BL in Transferrin Saturation (TSAT) | Week 68 | -7.279 Percentage of saturation | Standard Deviation 17.809 |
| Roxadustat | Change From BL in Transferrin Saturation (TSAT) | Week 76 | -7.156 Percentage of saturation | Standard Deviation 17.682 |
| Roxadustat | Change From BL in Transferrin Saturation (TSAT) | Week 84 | -7.867 Percentage of saturation | Standard Deviation 17.654 |
| Roxadustat | Change From BL in Transferrin Saturation (TSAT) | Week 92 | -6.996 Percentage of saturation | Standard Deviation 19.85 |
| Roxadustat | Change From BL in Transferrin Saturation (TSAT) | Week 100 | -8.379 Percentage of saturation | Standard Deviation 17.809 |
| Roxadustat | Change From BL in Transferrin Saturation (TSAT) | Week 104 | -7.650 Percentage of saturation | Standard Deviation 17.842 |
| Roxadustat | Change From BL in Transferrin Saturation (TSAT) | EOS | -5.466 Percentage of saturation | Standard Deviation 16.626 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Transferrin Saturation (TSAT) | EOS | -3.763 Percentage of saturation | Standard Deviation 17.813 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Transferrin Saturation (TSAT) | Week 4 | -2.331 Percentage of saturation | Standard Deviation 13.178 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Transferrin Saturation (TSAT) | Week 60 | -5.187 Percentage of saturation | Standard Deviation 16.097 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Transferrin Saturation (TSAT) | Week 8 | -3.128 Percentage of saturation | Standard Deviation 14.461 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Transferrin Saturation (TSAT) | Week 92 | -6.259 Percentage of saturation | Standard Deviation 16.605 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Transferrin Saturation (TSAT) | Week 12 | -3.189 Percentage of saturation | Standard Deviation 13.912 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Transferrin Saturation (TSAT) | Week 68 | -6.237 Percentage of saturation | Standard Deviation 15.934 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Transferrin Saturation (TSAT) | Week 20 | -4.398 Percentage of saturation | Standard Deviation 14.444 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Transferrin Saturation (TSAT) | Week 104 | -5.054 Percentage of saturation | Standard Deviation 17.195 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Transferrin Saturation (TSAT) | Week 28 | -3.829 Percentage of saturation | Standard Deviation 15.216 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Transferrin Saturation (TSAT) | Week 76 | -6.623 Percentage of saturation | Standard Deviation 16.395 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Transferrin Saturation (TSAT) | Week 36 | -4.022 Percentage of saturation | Standard Deviation 15.471 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Transferrin Saturation (TSAT) | Week 100 | -6.354 Percentage of saturation | Standard Deviation 17.147 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Transferrin Saturation (TSAT) | Week 44 | -5.254 Percentage of saturation | Standard Deviation 15.144 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Transferrin Saturation (TSAT) | Week 84 | -5.378 Percentage of saturation | Standard Deviation 17.771 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL in Transferrin Saturation (TSAT) | Week 52 | -5.788 Percentage of saturation | Standard Deviation 14.666 |
Secondary
Change From BL to Each Postdosing Study Visit in ApoB/ApoA1 Ratio
Baseline was defined as the value on Day 1. If baseline value was missing, the latest value prior to first study drug administration was used.
Time frame: Baseline and weeks 8, 28, 52, 104
Population: The analysis population was the FAS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Roxadustat | Change From BL to Each Postdosing Study Visit in ApoB/ApoA1 Ratio | Change from BL to Week 8 | -0.037 Ratio | Standard Deviation 0.147 |
| Roxadustat | Change From BL to Each Postdosing Study Visit in ApoB/ApoA1 Ratio | Change from BL to Week 28 | -0.034 Ratio | Standard Deviation 0.177 |
| Roxadustat | Change From BL to Each Postdosing Study Visit in ApoB/ApoA1 Ratio | Change from BL to Week 52 | -0.051 Ratio | Standard Deviation 0.191 |
| Roxadustat | Change From BL to Each Postdosing Study Visit in ApoB/ApoA1 Ratio | Change from BL to Week 104 | -0.062 Ratio | Standard Deviation 0.21 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL to Each Postdosing Study Visit in ApoB/ApoA1 Ratio | Change from BL to Week 104 | 0.007 Ratio | Standard Deviation 0.201 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL to Each Postdosing Study Visit in ApoB/ApoA1 Ratio | Change from BL to Week 8 | 0.013 Ratio | Standard Deviation 0.141 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL to Each Postdosing Study Visit in ApoB/ApoA1 Ratio | Change from BL to Week 52 | 0.007 Ratio | Standard Deviation 0.164 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL to Each Postdosing Study Visit in ApoB/ApoA1 Ratio | Change from BL to Week 28 | 0.002 Ratio | Standard Deviation 0.148 |
Secondary
Change From BL to Each Postdosing Study Visit in Apolipoproteins A1 (ApoA1)
Baseline was defined as the value on Day 1. If baseline value was missing, the latest value prior to first study drug administration was used regardless of fasting.
Time frame: Baseline and weeks 8, 28, 52, 104
Population: The analysis population was the FAS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Roxadustat | Change From BL to Each Postdosing Study Visit in Apolipoproteins A1 (ApoA1) | Change from BL to Week 8 | -0.114 g/L | Standard Deviation 0.197 |
| Roxadustat | Change From BL to Each Postdosing Study Visit in Apolipoproteins A1 (ApoA1) | Change from BL to Week 28 | -0.113 g/L | Standard Deviation 0.217 |
| Roxadustat | Change From BL to Each Postdosing Study Visit in Apolipoproteins A1 (ApoA1) | Change from BL to Week 52 | -0.097 g/L | Standard Deviation 0.23 |
| Roxadustat | Change From BL to Each Postdosing Study Visit in Apolipoproteins A1 (ApoA1) | Change from BL to Week 104 | -0.097 g/L | Standard Deviation 0.22 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL to Each Postdosing Study Visit in Apolipoproteins A1 (ApoA1) | Change from BL to Week 104 | -0.012 g/L | Standard Deviation 0.196 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL to Each Postdosing Study Visit in Apolipoproteins A1 (ApoA1) | Change from BL to Week 8 | -0.006 g/L | Standard Deviation 0.172 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL to Each Postdosing Study Visit in Apolipoproteins A1 (ApoA1) | Change from BL to Week 52 | -0.013 g/L | Standard Deviation 0.195 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL to Each Postdosing Study Visit in Apolipoproteins A1 (ApoA1) | Change from BL to Week 28 | -0.012 g/L | Standard Deviation 0.193 |
Secondary
Change From BL to Each Postdosing Study Visit in Apolipoproteins B (ApoB)
Baseline was defined as the value on Day 1. If baseline value was missing, the latest value prior to first study drug administration was used regardless of fasting.
Time frame: Baseline and weeks 8, 28, 52, 104
Population: The analysis population was the FAS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Roxadustat | Change From BL to Each Postdosing Study Visit in Apolipoproteins B (ApoB) | Change from BL to Week 8 | -11.03 mg/dL | Standard Deviation 18.49 |
| Roxadustat | Change From BL to Each Postdosing Study Visit in Apolipoproteins B (ApoB) | Change from BL to Week 28 | -11.18 mg/dL | Standard Deviation 20.39 |
| Roxadustat | Change From BL to Each Postdosing Study Visit in Apolipoproteins B (ApoB) | Change from BL to Week 52 | -13.18 mg/dL | Standard Deviation 20.67 |
| Roxadustat | Change From BL to Each Postdosing Study Visit in Apolipoproteins B (ApoB) | Change from BL to Week 104 | -13.50 mg/dL | Standard Deviation 24.94 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL to Each Postdosing Study Visit in Apolipoproteins B (ApoB) | Change from BL to Week 104 | -0.01 mg/dL | Standard Deviation 20 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL to Each Postdosing Study Visit in Apolipoproteins B (ApoB) | Change from BL to Week 8 | 1.00 mg/dL | Standard Deviation 14.34 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL to Each Postdosing Study Visit in Apolipoproteins B (ApoB) | Change from BL to Week 52 | -0.01 mg/dL | Standard Deviation 18.88 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL to Each Postdosing Study Visit in Apolipoproteins B (ApoB) | Change from BL to Week 28 | -0.12 mg/dL | Standard Deviation 16.91 |
Secondary
Change From BL to Each Post-dosing Study Visit in LDL-C/High-density Lipoprotein Cholesterol (HDL-C) Ratio
Baseline was defined as the value on Day 1. If baseline value was missing, the latest value prior to first study drug administration was used regardless of fasting.
Time frame: Baseline and weeks 8, 28, 52, 104
Population: The analysis population was the FAS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Roxadustat | Change From BL to Each Post-dosing Study Visit in LDL-C/High-density Lipoprotein Cholesterol (HDL-C) Ratio | Change from BL to Week 8 | -0.245 Ratio | Standard Deviation 0.818 |
| Roxadustat | Change From BL to Each Post-dosing Study Visit in LDL-C/High-density Lipoprotein Cholesterol (HDL-C) Ratio | Change from BL to Week 28 | -0.155 Ratio | Standard Deviation 1.046 |
| Roxadustat | Change From BL to Each Post-dosing Study Visit in LDL-C/High-density Lipoprotein Cholesterol (HDL-C) Ratio | Change from BL to Week 52 | -0.345 Ratio | Standard Deviation 0.904 |
| Roxadustat | Change From BL to Each Post-dosing Study Visit in LDL-C/High-density Lipoprotein Cholesterol (HDL-C) Ratio | Change from BL to Week 104 | -0.261 Ratio | Standard Deviation 1.167 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL to Each Post-dosing Study Visit in LDL-C/High-density Lipoprotein Cholesterol (HDL-C) Ratio | Change from BL to Week 104 | -0.013 Ratio | Standard Deviation 1.048 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL to Each Post-dosing Study Visit in LDL-C/High-density Lipoprotein Cholesterol (HDL-C) Ratio | Change from BL to Week 8 | -0.060 Ratio | Standard Deviation 0.726 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL to Each Post-dosing Study Visit in LDL-C/High-density Lipoprotein Cholesterol (HDL-C) Ratio | Change from BL to Week 52 | -0.078 Ratio | Standard Deviation 0.886 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL to Each Post-dosing Study Visit in LDL-C/High-density Lipoprotein Cholesterol (HDL-C) Ratio | Change from BL to Week 28 | -0.057 Ratio | Standard Deviation 0.922 |
Secondary
Change From BL to Each Postdosing Study Visit in Non-HDL Cholesterol
Baseline was defined as the value on Day 1. If baseline value was missing, the latest value prior to first study drug administration was used regardless of fasting.
Time frame: Baseline and weeks 8, 28, 52, 104
Population: The analysis population was the FAS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Roxadustat | Change From BL to Each Postdosing Study Visit in Non-HDL Cholesterol | Change from BL to Week 8 | -0.518 mmol/L | Standard Deviation 0.823 |
| Roxadustat | Change From BL to Each Postdosing Study Visit in Non-HDL Cholesterol | Change from BL to Week 28 | -0.540 mmol/L | Standard Deviation 0.907 |
| Roxadustat | Change From BL to Each Postdosing Study Visit in Non-HDL Cholesterol | Change from BL to Week 52 | -0.700 mmol/L | Standard Deviation 0.965 |
| Roxadustat | Change From BL to Each Postdosing Study Visit in Non-HDL Cholesterol | Change from BL to Week 104 | -0.788 mmol/L | Standard Deviation 1.024 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL to Each Postdosing Study Visit in Non-HDL Cholesterol | Change from BL to Week 104 | -0.240 mmol/L | Standard Deviation 1.01 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL to Each Postdosing Study Visit in Non-HDL Cholesterol | Change from BL to Week 8 | -0.107 mmol/L | Standard Deviation 0.701 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL to Each Postdosing Study Visit in Non-HDL Cholesterol | Change from BL to Week 52 | -0.229 mmol/L | Standard Deviation 0.886 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL to Each Postdosing Study Visit in Non-HDL Cholesterol | Change from BL to Week 28 | -0.127 mmol/L | Standard Deviation 0.789 |
Secondary
Change From BL to Each Post-dosing Study Visit in Total Cholesterol
Baseline assessment was the assessment from Day 1 visit. If baseline value was missing, then the latest screening period value was used as the baseline regardless of fasting status.
Time frame: Baseline and weeks 8, 28, 52, 104
Population: The analysis population was the FAS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Roxadustat | Change From BL to Each Post-dosing Study Visit in Total Cholesterol | Change from BL to Week 8 | -0.608 mmol/L | Standard Deviation 0.889 |
| Roxadustat | Change From BL to Each Post-dosing Study Visit in Total Cholesterol | Change from BL to Week 28 | -0.641 mmol/L | Standard Deviation 0.96 |
| Roxadustat | Change From BL to Each Post-dosing Study Visit in Total Cholesterol | Change from BL to Week 52 | -0.803 mmol/L | Standard Deviation 1.027 |
| Roxadustat | Change From BL to Each Post-dosing Study Visit in Total Cholesterol | Change from BL to Week 104 | -0.904 mmol/L | Standard Deviation 1.053 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL to Each Post-dosing Study Visit in Total Cholesterol | Change from BL to Week 104 | -0.277 mmol/L | Standard Deviation 1.002 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL to Each Post-dosing Study Visit in Total Cholesterol | Change from BL to Week 8 | -0.105 mmol/L | Standard Deviation 0.712 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL to Each Post-dosing Study Visit in Total Cholesterol | Change from BL to Week 52 | -0.241 mmol/L | Standard Deviation 0.906 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL to Each Post-dosing Study Visit in Total Cholesterol | Change from BL to Week 28 | -0.135 mmol/L | Standard Deviation 0.805 |
Secondary
Change From BL to the Average of Weeks 12 to 28 in Anemia Subscale (AnS) (Additional Concerns) of Functional Assessment of Cancer Therapy-Anemia (FACT-An) Score
Baseline FACT-An AnS was defined as the FACT-An AnS value on Day 1. Together with the Functional Assessment of Cancer Therapy - General (FACT-G), the Anemia Subscale (AnS) is referred to as the FACT-An Total. The AnS scale contains 13 fatigue specific items (the Fatigue Score) plus 7 items related to anemia. The Anemia AnS score range is 0 to 80. For the above score, a higher score indicates better QoL.
Time frame: Baseline and weeks 12 to 28
Population: The analysis population was the FAS.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Roxadustat | Change From BL to the Average of Weeks 12 to 28 in Anemia Subscale (AnS) (Additional Concerns) of Functional Assessment of Cancer Therapy-Anemia (FACT-An) Score | 0.400 Units on a scale |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL to the Average of Weeks 12 to 28 in Anemia Subscale (AnS) (Additional Concerns) of Functional Assessment of Cancer Therapy-Anemia (FACT-An) Score | 0.274 Units on a scale |
Comparison: The model includes treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline FACT-An Ans, baseline Hb, as continuous covariates.p-value: =0.84595% CI: [-1.135, 1.387]Mixed Models Analysis
Secondary
Change From BL to the Average of Weeks 12 to 28 in Euroqol Questionnaire-5 Dimensions 5 Levels (EQ-5D 5L) Visual Analogue Scale (VAS) Score
Baseline assessment was defined as the value on Day 1. The EuroQol Questionnaire -5 Dimensions -5 Levels (EQ-5D-5L) is a self-reported questionnaire, used as a measure of respondents' Health Related Quality of Life (HRQoL) and utility values. The EQ-5D consists of the descriptive system and the visual analogue scale (VAS). The EQ-5D descriptive system comprises 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, extreme problems. The VAS records the respondent's self rated health status on a graduated (0-100) scale, where the endpoints are labeled 'Best imaginable health state' and 'Worst imaginable health state' with higher scores for higher HRQoL.
Time frame: Baseline and weeks 12 to 28
Population: The analysis population was the FAS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Roxadustat | Change From BL to the Average of Weeks 12 to 28 in Euroqol Questionnaire-5 Dimensions 5 Levels (EQ-5D 5L) Visual Analogue Scale (VAS) Score | 3.041 Units on a scale | Standard Deviation 14.91 |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL to the Average of Weeks 12 to 28 in Euroqol Questionnaire-5 Dimensions 5 Levels (EQ-5D 5L) Visual Analogue Scale (VAS) Score | 2.735 Units on a scale | Standard Deviation 14.477 |
Secondary
Change From BL to the Average of Weeks 12 to 28 in SF-36 Physical Component Score (PCS)
Baseline SF-36 PCS was defined as the SF-36 PCS value on Day 1. SF-36 contains 36-item that measures 8 scales with scores ranging from 0-100: physical functioning (PF); role limitations due to physical health problems (RP); bodily pain (BP); social functioning (SF); general health perceptions (GH); role limitations due to emotional problems (RE); vitality, energy or fatigue (VT); and mental health (MH). These scores are normed to the US population (norm-based scoring had very little impact on results when data was collected in Western European countries) to have a mean of 50 and standard deviation of 10. The PCS was calculated based on all 8 scales and ranges from 5.02-79.78. For each of these above scales, higher scores always indicating better health status.
Time frame: Baseline and weeks 12 to 28
Population: The analysis population was the FAS.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Roxadustat | Change From BL to the Average of Weeks 12 to 28 in SF-36 Physical Component Score (PCS) | 0.560 Units on a scale |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL to the Average of Weeks 12 to 28 in SF-36 Physical Component Score (PCS) | 0.039 Units on a scale |
Comparison: The model includes treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline SF-36 PCS, baseline Hb, as continuous covariates.p-value: =0.16195% CI: [-0.208, 1.25]Mixed Models Analysis
Secondary
Change From BL to the Average Value of Weeks 12 to 28 in Total FACT-An Score
Baseline FACT-An Total Score was defined on Day 1. Total Fact-An score is composed of FACT-G and Ans scales. FACT-G contains 27 items that cover four dimensions of well-being: physical (PWB) - 7 items, functional (FWB) - 7 items, social/family (SWB) - 7 items, and emotional (EWB) - 6 items. The AnS scale contains 13 fatigue specific items (the Fatigue Score) plus 7 items related to anemia. The total score is obtained by summation of the scores from PWB, SWB, EWB, FWB and AnS. The FACT-An Total Score scale range is 0-188. A higher score indicates better QoL.
Time frame: Baseline and weeks 12 to 28
Population: The analysis population was the FAS.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Roxadustat | Change From BL to the Average Value of Weeks 12 to 28 in Total FACT-An Score | -0.501 Units on a scale |
| ESA (Erythropoiesis-Stimulating Agent) | Change From BL to the Average Value of Weeks 12 to 28 in Total FACT-An Score | -0.373 Units on a scale |
Comparison: The model includes treatment, visit, visit by treatment interaction, Previous ESA Treatment, region and history of CV disease as fixed class factors and baseline FACT-An Ans, baseline Hb, as continuous covariates.p-value: =0.92295% CI: [-2.703, 2.447]Mixed Models Analysis
Secondary
Hb Level Averaged Over Weeks 28 to 36, 44 to 52, and 96 to 104 Without Use of Rescue Therapy
Baseline Hb was defined as the mean of four latest central laboratory Hb values prior or on the same date as first study drug intake (pre-dose). Averaged Hb values over weeks 28-36, weeks 44-52 and weeks 96-104 are observed values.
Time frame: Weeks 28 to 36, 44 to 52, and 96 to 104
Population: The analysis population was the FAS.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Roxadustat | Hb Level Averaged Over Weeks 28 to 36, 44 to 52, and 96 to 104 Without Use of Rescue Therapy | Average Hb Over Weeks 28-36 | 11.183 g/dL |
| Roxadustat | Hb Level Averaged Over Weeks 28 to 36, 44 to 52, and 96 to 104 Without Use of Rescue Therapy | Average Hb Over Weeks 44-52 | 11.099 g/dL |
| Roxadustat | Hb Level Averaged Over Weeks 28 to 36, 44 to 52, and 96 to 104 Without Use of Rescue Therapy | Average Hb Over Weeks 96-104 | 11.007 g/dL |
| ESA (Erythropoiesis-Stimulating Agent) | Hb Level Averaged Over Weeks 28 to 36, 44 to 52, and 96 to 104 Without Use of Rescue Therapy | Average Hb Over Weeks 28-36 | 10.946 g/dL |
| ESA (Erythropoiesis-Stimulating Agent) | Hb Level Averaged Over Weeks 28 to 36, 44 to 52, and 96 to 104 Without Use of Rescue Therapy | Average Hb Over Weeks 44-52 | 10.994 g/dL |
| ESA (Erythropoiesis-Stimulating Agent) | Hb Level Averaged Over Weeks 28 to 36, 44 to 52, and 96 to 104 Without Use of Rescue Therapy | Average Hb Over Weeks 96-104 | 10.858 g/dL |
Comparison: Weeks 28-36 - The model includes treatment arm, region, CV History, previous ESA treatment, visits and visit by treatment as categorical variables and baseline Hb as continuous variable.p-value: <0.00195% CI: [0.127, 0.347]Mixed Models Analysis
Comparison: Weeks 44-52 - The model includes treatment arm, region, CV History, previous ESA treatment, visits and visit by treatment as categorical variables and baseline Hb as continuous variable.p-value: =0.08695% CI: [-0.015, 0.225]Mixed Models Analysis
Comparison: Weeks 96-104 - The model includes treatment arm, region, CV History, previous ESA treatment, visits and visit by treatment as categorical variables and baseline Hb as continuous variable.p-value: =0.03195% CI: [0.014, 0.284]Mixed Models Analysis
Secondary
Mean Monthly Intravenous (IV) Iron Per Participant During Weeks 37-52 and Weeks 53-104
Participants with no or missing medication records of IV Iron had their monthly IV Iron use set to 0 mg.
Time frame: Weeks 37-52 and weeks 53-104
Population: The analysis population was the FAS.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Roxadustat | Mean Monthly Intravenous (IV) Iron Per Participant During Weeks 37-52 and Weeks 53-104 | Weeks 37-52 | 34.9 mg per month |
| Roxadustat | Mean Monthly Intravenous (IV) Iron Per Participant During Weeks 37-52 and Weeks 53-104 | Weeks 53-104 | 49.5 mg per month |
| ESA (Erythropoiesis-Stimulating Agent) | Mean Monthly Intravenous (IV) Iron Per Participant During Weeks 37-52 and Weeks 53-104 | Weeks 53-104 | 98.1 mg per month |
| ESA (Erythropoiesis-Stimulating Agent) | Mean Monthly Intravenous (IV) Iron Per Participant During Weeks 37-52 and Weeks 53-104 | Weeks 37-52 | 70.0 mg per month |
Comparison: Weeks 37-52 - Participants with no or missing medication records of IV Iron had their monthly IV Iron use set to 0 mg. The model includes treatment arm, region, CV History, previous ESA treatment as categorical variables and baseline Hb as continuous variable.p-value: <0.00195% CI: [-51.8, -18.4]ANCOVA
Comparison: Weeks 53-104 - Participants with no or missing medication records of IV Iron had their monthly IV Iron use set to 0 mg. The model includes treatment arm, region, CV History, previous ESA treatment as categorical variables and baseline Hb as continuous variable.p-value: <0.00195% CI: [-70.3, -27]ANCOVA
Secondary
Mean Monthly Intravenous (IV) Iron Use
Participants with no or missing medication records of IV Iron have their monthly IV Iron use set to 0 mg. For participants who took IV Iron, but without a dosing frequency, the average values were set to missing.
Time frame: Day 1 to week 36
Population: The analysis population was the FAS, with participants who had available data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Roxadustat | Mean Monthly Intravenous (IV) Iron Use | 21.6 mg per month |
| ESA (Erythropoiesis-Stimulating Agent) | Mean Monthly Intravenous (IV) Iron Use | 53.5 mg per month |
Comparison: The model includes treatment arm, region, CV History, previous ESA treatment as categorical variables and baseline Hb as continuous variable.p-value: <0.00195% CI: [-41.4, -22.4]ANCOVA
Secondary
Mean Monthly Number of RBC Packs Per Participant
During efficacy emergent period, the mean monthly number of RBC packs was calculated as the sum of blood volume and units transfused between the first dose and up to the last dose in the period divided by duration of efficacy emergent period (in days) divided by 28 days. Participants without medication records of RBC have their number of RBC packs and volume set to 0.
Time frame: Baseline to EOT (Up to week 104)
Population: The analysis population was the FAS.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Roxadustat | Mean Monthly Number of RBC Packs Per Participant | 0.026 RBC packs per month |
| ESA (Erythropoiesis-Stimulating Agent) | Mean Monthly Number of RBC Packs Per Participant | 0.032 RBC packs per month |
Comparison: The model included treatment arm, region, CV History, previous ESA treatment as categorical variables and baseline Hb as continuous variable.p-value: =0.50795% CI: [-0.02, 0.01]ANCOVA
Secondary
Mean Monthly Volume of RBC Transfusion Per Participant
During Efficacy Emergent Period, the mean monthly volume of blood transfused was calculated as the sum of blood volume and units transfused between the first dose and up to the last dose in the period divided by duration of efficacy emergent period (in days) divided by 28 days. The Efficacy Emergent Period was defined as the evaluation period from the Analysis date of first dose intake up to EOT Visit or last non-missing Hb assessment (for participants who died during the treatment period).
Time frame: Baseline to EOT (Up to week 104)
Population: The analysis population was the FAS.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Roxadustat | Mean Monthly Volume of RBC Transfusion Per Participant | 6.061 mL per month |
| ESA (Erythropoiesis-Stimulating Agent) | Mean Monthly Volume of RBC Transfusion Per Participant | 5.929 mL per month |
Comparison: The model included treatment arm, region, CV History, previous ESA treatment as categorical variables and baseline Hb as continuous variable.p-value: =0.94995% CI: [-3.9, 4.16]ANCOVA
Secondary
Number of Days of Hospitalization Per Year
The number of days of hospitalizations per year was calculated as the sum of the durations of all non-HD hospitalizations in days (Date of discharge - Date of admission + 1)\] / (duration of efficacy emergent period in days / 365.25). In case of missing dates, the hospitalization duration was imputed by the average duration per stay derived from the participants with non-missing duration within the same treatment group.
Time frame: Baseline to EOT (Up to week 104)
Population: The analysis population was the FAS, with participants who had available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Roxadustat | Number of Days of Hospitalization Per Year | 12.186 Days per year | Standard Deviation 34.121 |
| ESA (Erythropoiesis-Stimulating Agent) | Number of Days of Hospitalization Per Year | 7.868 Days per year | Standard Deviation 22.948 |
Secondary
Number of Hospitalizations
The number of hospitalizations per participant were calculated during the Efficacy Emergent Period. The Efficacy Emergent Period was defined as the evaluation period from the Analysis date of first dose intake up to EOT Visit or last non-missing Hb assessment (for participants who died during the treatment period). It included all Non-Hemodialysis (HD) hospitalizations. The HD days were not counted as hospitalizations, even when performed overnight.
Time frame: Baseline to End of Treatment (EOT) (Up to week 104)
Population: The analysis population was the FAS, with participants who had available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Roxadustat | Number of Hospitalizations | 0.9 Hospitalizations | Standard Deviation 1.3 |
| ESA (Erythropoiesis-Stimulating Agent) | Number of Hospitalizations | 0.9 Hospitalizations | Standard Deviation 1.5 |
Secondary
Number of Participants With CKD Who Achieved Antihypertensive Treatment Goal
Achieved antihypertensive treatment goal was defined as SBP \< 140 mmHg and DBP \< 90 mmHg over an evaluation period based on the average of available values in weeks 12-28 (pre-dialysis).
Time frame: Weeks 12 to 28
Population: The analysis population was the FAS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Roxadustat | Number of Participants With CKD Who Achieved Antihypertensive Treatment Goal | Antihypertensive Treatment Achievement-Missing | 19 Number of participants |
| Roxadustat | Number of Participants With CKD Who Achieved Antihypertensive Treatment Goal | Antihypertensive Treatment Achievement - Yes | 264 Number of participants |
| Roxadustat | Number of Participants With CKD Who Achieved Antihypertensive Treatment Goal | Antihypertensive Treatment Achievement - No | 130 Number of participants |
| ESA (Erythropoiesis-Stimulating Agent) | Number of Participants With CKD Who Achieved Antihypertensive Treatment Goal | Antihypertensive Treatment Achievement - No | 149 Number of participants |
| ESA (Erythropoiesis-Stimulating Agent) | Number of Participants With CKD Who Achieved Antihypertensive Treatment Goal | Antihypertensive Treatment Achievement - Yes | 261 Number of participants |
| ESA (Erythropoiesis-Stimulating Agent) | Number of Participants With CKD Who Achieved Antihypertensive Treatment Goal | Antihypertensive Treatment Achievement-Missing | 10 Number of participants |
Secondary
Number of Participants With Mean LDL Cholesterol < 100 mg/dL Over Weeks 12 to 28
Missing category for Fasting Only includes non-fasting participants and the participants with missing values.
Time frame: Weeks 12 to 28
Population: The analysis population was the FAS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Roxadustat | Number of Participants With Mean LDL Cholesterol < 100 mg/dL Over Weeks 12 to 28 | Yes [Regardless of Fasting Status] | 275 Number of participants |
| Roxadustat | Number of Participants With Mean LDL Cholesterol < 100 mg/dL Over Weeks 12 to 28 | No [Regardless of Fasting Status] | 119 Number of participants |
| Roxadustat | Number of Participants With Mean LDL Cholesterol < 100 mg/dL Over Weeks 12 to 28 | Missing [Regardless of Fasting Status] | 19 Number of participants |
| Roxadustat | Number of Participants With Mean LDL Cholesterol < 100 mg/dL Over Weeks 12 to 28 | Yes [Fasting Only] | 111 Number of participants |
| Roxadustat | Number of Participants With Mean LDL Cholesterol < 100 mg/dL Over Weeks 12 to 28 | No [Fasting Only] | 61 Number of participants |
| Roxadustat | Number of Participants With Mean LDL Cholesterol < 100 mg/dL Over Weeks 12 to 28 | Missing [Fasting Only] | 241 Number of participants |
| ESA (Erythropoiesis-Stimulating Agent) | Number of Participants With Mean LDL Cholesterol < 100 mg/dL Over Weeks 12 to 28 | No [Fasting Only] | 80 Number of participants |
| ESA (Erythropoiesis-Stimulating Agent) | Number of Participants With Mean LDL Cholesterol < 100 mg/dL Over Weeks 12 to 28 | Yes [Regardless of Fasting Status] | 231 Number of participants |
| ESA (Erythropoiesis-Stimulating Agent) | Number of Participants With Mean LDL Cholesterol < 100 mg/dL Over Weeks 12 to 28 | Yes [Fasting Only] | 85 Number of participants |
| ESA (Erythropoiesis-Stimulating Agent) | Number of Participants With Mean LDL Cholesterol < 100 mg/dL Over Weeks 12 to 28 | No [Regardless of Fasting Status] | 181 Number of participants |
| ESA (Erythropoiesis-Stimulating Agent) | Number of Participants With Mean LDL Cholesterol < 100 mg/dL Over Weeks 12 to 28 | Missing [Fasting Only] | 255 Number of participants |
| ESA (Erythropoiesis-Stimulating Agent) | Number of Participants With Mean LDL Cholesterol < 100 mg/dL Over Weeks 12 to 28 | Missing [Regardless of Fasting Status] | 8 Number of participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Safety was assessed by evaluation of the following variables: (TEAEs; frequency, severity, seriousness, and relationship to study drug), Vital signs (systolic and diastolic blood pressure, pulse, respiratory rate and weight), Clinical laboratory variables (hematology, biochemistry including liver enzymes and total bilirubin, and urinalysis), Physical examination, 12-lead electrocardiogram (ECG) and Vascular Access Thrombosis. All AEs collected during the Safety Emergent Period were counted as TEAE. The TEAE was defined as an adverse event (AE) if it was observed after starting administration of the roxadustat or ESA. Any clinically significant abnormalities were reported as an AEs. All reported deaths after the first study drug administration and up to 28 days after the Analysis Date of Last Dose and considering last dosing frequency.
Time frame: Baseline up to EOS (Up to week 108)
Population: The analysis population was the Safety Analysis Set (SAF) which consisted of all randomized participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Roxadustat | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Serious TEAE | 210 Participants |
| Roxadustat | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE Leading to Withdrawal of Treatment | 35 Participants |
| Roxadustat | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Drug-Related TEAE | 77 Participants |
| Roxadustat | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Drug-Related TEAE Leading to Withdraw of Treatment | 9 Participants |
| Roxadustat | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Drug-Related Serious TEAE | 33 Participants |
| Roxadustat | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE NCI CTC Grades 3 or Higher | 181 Participants |
| Roxadustat | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE | 359 Participants |
| Roxadustat | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Death During the Safety Emergent Period | 64 Participants |
| Roxadustat | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE Leading to Death | 67 Participants |
| Roxadustat | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Death | 78 Participants |
| Roxadustat | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Drug-Related TEAE Leading to Death | 5 Participants |
| ESA (Erythropoiesis-Stimulating Agent) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Death | 59 Participants |
| ESA (Erythropoiesis-Stimulating Agent) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE | 361 Participants |
| ESA (Erythropoiesis-Stimulating Agent) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Drug-Related TEAE | 35 Participants |
| ESA (Erythropoiesis-Stimulating Agent) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Serious TEAE | 189 Participants |
| ESA (Erythropoiesis-Stimulating Agent) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Drug-Related Serious TEAE | 10 Participants |
| ESA (Erythropoiesis-Stimulating Agent) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Drug-Related TEAE Leading to Death | 2 Participants |
| ESA (Erythropoiesis-Stimulating Agent) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE Leading to Withdrawal of Treatment | 16 Participants |
| ESA (Erythropoiesis-Stimulating Agent) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Drug-Related TEAE Leading to Withdraw of Treatment | 1 Participants |
| ESA (Erythropoiesis-Stimulating Agent) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE NCI CTC Grades 3 or Higher | 149 Participants |
| ESA (Erythropoiesis-Stimulating Agent) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Death During the Safety Emergent Period | 51 Participants |
| ESA (Erythropoiesis-Stimulating Agent) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | TEAE Leading to Death | 55 Participants |
Secondary
Percentage of Hb Values ≥ 10 g/dL in Weeks 28 to 36, 44 to 52, and 96 to 104 Without Use of Rescue Therapy
Percentage for each participant was calculated as Number of Hb values \>= 10.0 g/dL / Total number of Hb values\*100 in weeks 28 to 36, 44 to 52 and 96 to 104 without use of rescue therapy within 6 weeks prior to and during the 8 week evaluation period.
Time frame: Weeks 28-36, 44-52 and 96-104
Population: The analysis population was the FAS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Roxadustat | Percentage of Hb Values ≥ 10 g/dL in Weeks 28 to 36, 44 to 52, and 96 to 104 Without Use of Rescue Therapy | Weeks 28-36 | 93.002 percentage of Hb values | Standard Deviation 18.32 |
| Roxadustat | Percentage of Hb Values ≥ 10 g/dL in Weeks 28 to 36, 44 to 52, and 96 to 104 Without Use of Rescue Therapy | Weeks 44-52 | 89.421 percentage of Hb values | Standard Deviation 24.267 |
| Roxadustat | Percentage of Hb Values ≥ 10 g/dL in Weeks 28 to 36, 44 to 52, and 96 to 104 Without Use of Rescue Therapy | Weeks 96-104 | 88.858 percentage of Hb values | Standard Deviation 24.708 |
| ESA (Erythropoiesis-Stimulating Agent) | Percentage of Hb Values ≥ 10 g/dL in Weeks 28 to 36, 44 to 52, and 96 to 104 Without Use of Rescue Therapy | Weeks 28-36 | 87.286 percentage of Hb values | Standard Deviation 25.114 |
| ESA (Erythropoiesis-Stimulating Agent) | Percentage of Hb Values ≥ 10 g/dL in Weeks 28 to 36, 44 to 52, and 96 to 104 Without Use of Rescue Therapy | Weeks 44-52 | 86.914 percentage of Hb values | Standard Deviation 25.366 |
| ESA (Erythropoiesis-Stimulating Agent) | Percentage of Hb Values ≥ 10 g/dL in Weeks 28 to 36, 44 to 52, and 96 to 104 Without Use of Rescue Therapy | Weeks 96-104 | 83.543 percentage of Hb values | Standard Deviation 30.296 |
Secondary
Percentage of Hb Values Within 10.0 to 12.0 g/dL in Weeks 28 to 36, 44 to 52, and 96 to 104 Without Use of Rescue Therapy
Percentage for each participant was calculated as Number of Hb values within 10.0-12.0 g/dL / Total number of Hb values\*100 in weeks 28 to 36, 44 to 52 and 96 to 104 without use of rescue therapy within 6 weeks prior to and during the 8 week evaluation period.
Time frame: Weeks 28-36, 44-52 and 96-104
Population: The analysis population was the FAS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Roxadustat | Percentage of Hb Values Within 10.0 to 12.0 g/dL in Weeks 28 to 36, 44 to 52, and 96 to 104 Without Use of Rescue Therapy | Weeks 28-36 | 76.326 percentage of Hb values | Standard Deviation 28.175 |
| Roxadustat | Percentage of Hb Values Within 10.0 to 12.0 g/dL in Weeks 28 to 36, 44 to 52, and 96 to 104 Without Use of Rescue Therapy | Weeks 44-52 | 75.891 percentage of Hb values | Standard Deviation 31.047 |
| Roxadustat | Percentage of Hb Values Within 10.0 to 12.0 g/dL in Weeks 28 to 36, 44 to 52, and 96 to 104 Without Use of Rescue Therapy | Weeks 96-104 | 76.522 percentage of Hb values | Standard Deviation 30.378 |
| ESA (Erythropoiesis-Stimulating Agent) | Percentage of Hb Values Within 10.0 to 12.0 g/dL in Weeks 28 to 36, 44 to 52, and 96 to 104 Without Use of Rescue Therapy | Weeks 28-36 | 76.098 percentage of Hb values | Standard Deviation 28.991 |
| ESA (Erythropoiesis-Stimulating Agent) | Percentage of Hb Values Within 10.0 to 12.0 g/dL in Weeks 28 to 36, 44 to 52, and 96 to 104 Without Use of Rescue Therapy | Weeks 44-52 | 74.634 percentage of Hb values | Standard Deviation 30.589 |
| ESA (Erythropoiesis-Stimulating Agent) | Percentage of Hb Values Within 10.0 to 12.0 g/dL in Weeks 28 to 36, 44 to 52, and 96 to 104 Without Use of Rescue Therapy | Weeks 96-104 | 73.690 percentage of Hb values | Standard Deviation 33.04 |
Secondary
Percentage of Participants With a Hb Response During Weeks 28 and 36 Regardless of Use of Rescue Therapy
Hb response was defined as mean Hb during weeks 28 to 36 within the target range of 10.0 to 12.0 g/dL. The percentages and 95% CI are unadjusted, the exact method of Clopper-Pearson was used for 95% CI.
Time frame: Weeks 28 to 36
Population: The analysis population was the FAS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Roxadustat | Percentage of Participants With a Hb Response During Weeks 28 and 36 Regardless of Use of Rescue Therapy | 83.1 Percentage of participants |
| ESA (Erythropoiesis-Stimulating Agent) | Percentage of Participants With a Hb Response During Weeks 28 and 36 Regardless of Use of Rescue Therapy | 82.1 Percentage of participants |
Comparison: A generalized linear model was used to estimate the difference in response rates between the arms, as an approximation for the Miettinen and Nurminen method, adjusting for following covariates: region, previous ESA treatment, cardiovascular history and baseline Hb as categorical variables.p-value: =0.60995% CI: [-3.8, 6.5]Miettinen and Nurminen method
Secondary
Percentage of Participants With Hb Response During Weeks 28 to 36
Hb response during weeks 28-36, was defined as mean Hb from 10-12 g/dL without receiving rescue therapy in the 6 weeks prior to, or during, the evaluation period. The percentages and 95% CI were unadjusted, the exact method of Clopper-Pearson was used for 95% CI. The Efficacy Emergent Period was defined as the evaluation period from the Analysis date of first dose intake up to end of treatment (EOT) Visit or last non-missing Hb assessment (for participants who died during the treatment period).
Time frame: Weeks 28 to 36
Population: The analysis population was the PPS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Roxadustat | Percentage of Participants With Hb Response During Weeks 28 to 36 | 84.2 Percentage of participants |
| ESA (Erythropoiesis-Stimulating Agent) | Percentage of Participants With Hb Response During Weeks 28 to 36 | 82.4 Percentage of participants |
Comparison: A generalized linear model was used to estimate the difference in response rates between the arms, as an approximation for the Miettinen and Nurminen method, adjusting for following covariates: region, previous ESA treatment, cardiovascular history and baseline Hb as categorical variables.p-value: <0.0595% CI: [-2.9, 7.6]Miettinen and Nurminen
Secondary
Percentage of Participants With Improvements Measured by Patients' Global Impression of Change (PGIC)
The PGIC is a patient-rated instrument that measures change in participant's overall status on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse), when compared to the start of treatment. The percentage of participants presented includes very much improved, much improved and minimally improved.
Time frame: Baseline and weeks 8, 12, 28, 36, 52, 76, 104
Population: The analysis population was the FAS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Roxadustat | Percentage of Participants With Improvements Measured by Patients' Global Impression of Change (PGIC) | Week 28 | 62.3 Percentage of participants |
| Roxadustat | Percentage of Participants With Improvements Measured by Patients' Global Impression of Change (PGIC) | Week 52 | 57.1 Percentage of participants |
| Roxadustat | Percentage of Participants With Improvements Measured by Patients' Global Impression of Change (PGIC) | Week 12 | 65.5 Percentage of participants |
| Roxadustat | Percentage of Participants With Improvements Measured by Patients' Global Impression of Change (PGIC) | Week 76 | 61.2 Percentage of participants |
| Roxadustat | Percentage of Participants With Improvements Measured by Patients' Global Impression of Change (PGIC) | Week 36 | 60.4 Percentage of participants |
| Roxadustat | Percentage of Participants With Improvements Measured by Patients' Global Impression of Change (PGIC) | Week 104 | 61.6 Percentage of participants |
| Roxadustat | Percentage of Participants With Improvements Measured by Patients' Global Impression of Change (PGIC) | Week 8 | 59.6 Percentage of participants |
| ESA (Erythropoiesis-Stimulating Agent) | Percentage of Participants With Improvements Measured by Patients' Global Impression of Change (PGIC) | Week 104 | 51.3 Percentage of participants |
| ESA (Erythropoiesis-Stimulating Agent) | Percentage of Participants With Improvements Measured by Patients' Global Impression of Change (PGIC) | Week 8 | 49.5 Percentage of participants |
| ESA (Erythropoiesis-Stimulating Agent) | Percentage of Participants With Improvements Measured by Patients' Global Impression of Change (PGIC) | Week 12 | 49.5 Percentage of participants |
| ESA (Erythropoiesis-Stimulating Agent) | Percentage of Participants With Improvements Measured by Patients' Global Impression of Change (PGIC) | Week 28 | 57.1 Percentage of participants |
| ESA (Erythropoiesis-Stimulating Agent) | Percentage of Participants With Improvements Measured by Patients' Global Impression of Change (PGIC) | Week 36 | 56.3 Percentage of participants |
| ESA (Erythropoiesis-Stimulating Agent) | Percentage of Participants With Improvements Measured by Patients' Global Impression of Change (PGIC) | Week 52 | 55.3 Percentage of participants |
| ESA (Erythropoiesis-Stimulating Agent) | Percentage of Participants With Improvements Measured by Patients' Global Impression of Change (PGIC) | Week 76 | 51.9 Percentage of participants |
Secondary
Percentage of Participants With Oral Iron Use Only
Percentage of participants with/without IV iron only was calculated based on total number of participants within the Efficacy Emergent Period. The Efficacy Emergent Period is defined as the evaluation period from the Analysis date of first dose intake up to EOT Visit or last non-missing Hb assessment (for participants who died during the treatment period).
Time frame: Baseline to EOT (Up to week 104)
Population: The analysis population was the FAS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Roxadustat | Percentage of Participants With Oral Iron Use Only | 31.0 Percentage of participants |
| ESA (Erythropoiesis-Stimulating Agent) | Percentage of Participants With Oral Iron Use Only | 11.7 Percentage of participants |
Secondary
Time to First Hospitalization
Time to first hospitalization in years was defined in years as: (First event date during the Efficacy Emergent Period - Analysis date of First dose intake +1)/365.25, and the 'First event date' was defined as 'Date of first Admission and 'Analysis Date of first dose intake. For participants without hospitalization, the time to censoring was calculated as: (Date of End of Efficacy Emergent Period - Analysis Date of first dose intake + 1) / 365.25. Date of End of Efficacy Emergent Period was defined as as the treatment period up to the EOT visit. For participants who have experienced more than one hospitalization, only their first event following study treatment was used. Data reported was analyzed by Kaplan-Meier estimate for cumulative proportion and the 95% confidence interval was calculated with Greenwood's formula.
Time frame: Baseline to EOT (Up to week 104)
Population: The analysis population was the FAS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Roxadustat | Time to First Hospitalization | Year 2 | 52.6 Percentage of participants |
| Roxadustat | Time to First Hospitalization | Year 1 | 32.0 Percentage of participants |
| Roxadustat | Time to First Hospitalization | Year 0.5 | 19.4 Percentage of participants |
| Roxadustat | Time to First Hospitalization | Year 1.5 | 43.5 Percentage of participants |
| ESA (Erythropoiesis-Stimulating Agent) | Time to First Hospitalization | Year 0.5 | 18.3 Percentage of participants |
| ESA (Erythropoiesis-Stimulating Agent) | Time to First Hospitalization | Year 1 | 32.7 Percentage of participants |
| ESA (Erythropoiesis-Stimulating Agent) | Time to First Hospitalization | Year 2 | 48.3 Percentage of participants |
| ESA (Erythropoiesis-Stimulating Agent) | Time to First Hospitalization | Year 1.5 | 41.9 Percentage of participants |
Comparison: Hazard Ratio was calculated using stratified Cox Proportional Hazards regression stratifying on region, CV history, previous ESA treatment and adjusting on Hb at baseline as continuous covariate. Superiority was declared if the upper bound of the 95% CI was below 1.0.p-value: =0.16495% CI: [0.943, 1.411]Regression, Cox
Secondary
Time to First Occurrence of an Increase in Blood Pressure
Increase in Blood Pressure was defined as either: SBP ≥ 170 mmHg and an increase from BL ≥ 20 mmHg, or as: DBP ≥ 100 mmHg and an increase from BL ≥ 15 mmHg. Data reported was analyzed by Kaplan-Meier estimate for cumulative proportion and the 95% confidence interval was calculated with Greenwood's formula.
Time frame: Weeks 1 to 36
Population: The analysis population was the FAS, with participants who had available data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Roxadustat | Time to First Occurrence of an Increase in Blood Pressure | Week 12 | 11.6 Percentage of participants |
| Roxadustat | Time to First Occurrence of an Increase in Blood Pressure | Week 24 | 16.1 Percentage of participants |
| Roxadustat | Time to First Occurrence of an Increase in Blood Pressure | Week 36 | 21.2 Percentage of participants |
| ESA (Erythropoiesis-Stimulating Agent) | Time to First Occurrence of an Increase in Blood Pressure | Week 12 | 12.0 Percentage of participants |
| ESA (Erythropoiesis-Stimulating Agent) | Time to First Occurrence of an Increase in Blood Pressure | Week 24 | 16.2 Percentage of participants |
| ESA (Erythropoiesis-Stimulating Agent) | Time to First Occurrence of an Increase in Blood Pressure | Week 36 | 24.1 Percentage of participants |
Comparison: Hazard Ratio was calculated using stratified Cox Proportional Hazards regression stratifying on region, CV history, previous ESA treatment, and adjusting on Hb at baseline as continuous covariate. Superiority was declared if the upper bound of the 95% CI is lower than 1.p-value: =0.58295% CI: [0.668, 1.254]Regression, Cox
Secondary
Time to First Occurrence of an Increase in Blood Pressure
Increase in Blood Pressure was defined as either: Systolic Blood Pressure (SBP) ≥ 170 mmHg and an increase from BL ≥ 20 mmHg, or as: Diastolic Blood Pressure (DBP) ≥ 100 mmHg and an increase from BL ≥ 15 mmHg. For participants who have experienced more than one event, only their first event following study treatment was used. Data reported was analyzed by Kaplan-Meier estimate for cumulative proportion and the 95% confidence interval was calculated with Greenwood's formula.
Time frame: Weeks 1 to 36
Population: The analysis population was the PPS, with participants who had available data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Roxadustat | Time to First Occurrence of an Increase in Blood Pressure | Week 12 | 11.7 Percentage of participants |
| Roxadustat | Time to First Occurrence of an Increase in Blood Pressure | Week 24 | 15.9 Percentage of participants |
| Roxadustat | Time to First Occurrence of an Increase in Blood Pressure | Week 36 | 21.1 Percentage of participants |
| ESA (Erythropoiesis-Stimulating Agent) | Time to First Occurrence of an Increase in Blood Pressure | Week 12 | 11.1 Percentage of participants |
| ESA (Erythropoiesis-Stimulating Agent) | Time to First Occurrence of an Increase in Blood Pressure | Week 24 | 15.4 Percentage of participants |
| ESA (Erythropoiesis-Stimulating Agent) | Time to First Occurrence of an Increase in Blood Pressure | Week 36 | 23.5 Percentage of participants |
Comparison: Hazard Ratio was calculated using stratified Cox Proportional Hazards regression stratifying on region, CV history, previous ESA treatment, and adjusting on Hb at baseline as continuous covariate. Non-inferiority was declared if the upper bound of the 95% CI is below 1.3.p-value: <0.0595% CI: [0.669, 1.276]Regression, Cox
Secondary
Time to First RBC Transfusion
For participants who have experienced more than one RBC transfusion, only their first event following study treatment was used. For RBC transfusions, when the number of units was not given but the volume transfused was, the number of units were estimated by volume transfused/250 mL (for transfusion of packed cell units) or volume transfused/500 mL (for transfusion of full blood). Data reported was analyzed by Kaplan-Meier estimate for cumulative proportion and the 95% confidence interval was calculated with Greenwood's formula.
Time frame: Baseline to EOT (Up to week 104)
Population: The analysis population was the FAS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Roxadustat | Time to First RBC Transfusion | Year 0.5 | 3.6 Percentage of participants |
| Roxadustat | Time to First RBC Transfusion | Year 1 | 7.4 Percentage of participants |
| Roxadustat | Time to First RBC Transfusion | Year 1.5 | 10.0 Percentage of participants |
| Roxadustat | Time to First RBC Transfusion | Year 2 | 11.4 Percentage of participants |
| ESA (Erythropoiesis-Stimulating Agent) | Time to First RBC Transfusion | Year 2 | 14.4 Percentage of participants |
| ESA (Erythropoiesis-Stimulating Agent) | Time to First RBC Transfusion | Year 0.5 | 3.2 Percentage of participants |
| ESA (Erythropoiesis-Stimulating Agent) | Time to First RBC Transfusion | Year 1.5 | 10.9 Percentage of participants |
| ESA (Erythropoiesis-Stimulating Agent) | Time to First RBC Transfusion | Year 1 | 8.4 Percentage of participants |
Comparison: Hazard Ratio was calculated using stratified Cox Proportional Hazards regression stratifying on region, CV history, previous ESA treatment, and adjusting on Hb at baseline as continuous covariate. Superiority was declared if the upper bound of the 95% CI was below 1.0.p-value: =0.50195% CI: [0.573, 1.313]Regression, Cox
Secondary
Time to First Use of IV Iron Supplementation
For participants who have received more than one IV iron, only their first event following study treatment was used. Data reported was analyzed by Kaplan-Meier estimate for cumulative proportion and the 95% confidence interval was calculated with Greenwood's formula.
Time frame: Baseline to EOT (Up to week 104)
Population: The analysis population was the FAS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Roxadustat | Time to First Use of IV Iron Supplementation | Year 0.5 | 11.2 Percentage of participants |
| Roxadustat | Time to First Use of IV Iron Supplementation | Year 1 | 17.4 Percentage of participants |
| Roxadustat | Time to First Use of IV Iron Supplementation | Year 1.5 | 23.6 Percentage of participants |
| Roxadustat | Time to First Use of IV Iron Supplementation | Year 2 | 33.3 Percentage of participants |
| ESA (Erythropoiesis-Stimulating Agent) | Time to First Use of IV Iron Supplementation | Year 2 | 59.3 Percentage of participants |
| ESA (Erythropoiesis-Stimulating Agent) | Time to First Use of IV Iron Supplementation | Year 0.5 | 33.5 Percentage of participants |
| ESA (Erythropoiesis-Stimulating Agent) | Time to First Use of IV Iron Supplementation | Year 1.5 | 55.0 Percentage of participants |
| ESA (Erythropoiesis-Stimulating Agent) | Time to First Use of IV Iron Supplementation | Year 1 | 44.1 Percentage of participants |
Comparison: Hazard Ratio was calculated using stratified Cox Proportional Hazards regression stratifying on region, CV history, previous ESA treatment and adjusting on Hb at baseline as continuous covariate. Superiority was declared if the upper bound of the 95% CI was below 1.0.p-value: <0.00195% CI: [0.291, 0.465]Regression, Cox
Secondary
Time to First Use of Rescue Therapy
Rescue therapy was defined as red blood cell (RBC) transfusion for both treatment groups and ESA for roxadustat participants. Only rescue medication that was started during the study treatment and up to end of efficacy emergent period was taken into account and considered as use of rescue medication. For participants who have experienced more than one use of rescue therapy, only their first event following study treatment was used. Data reported was analyzed by Kaplan-Meier estimate for cumulative proportion and the 95% confidence interval was calculated with Greenwood's formula.
Time frame: Baseline to EOT (Up to week 104)
Population: The analysis population was the FAS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Roxadustat | Time to First Use of Rescue Therapy | Year 1.5 | 11.4 Percentage of participants |
| Roxadustat | Time to First Use of Rescue Therapy | Year 0.5 | 3.9 Percentage of participants |
| Roxadustat | Time to First Use of Rescue Therapy | Year 2 | 12.8 Percentage of participants |
| Roxadustat | Time to First Use of Rescue Therapy | Year 1 | 8.2 Percentage of participants |
| ESA (Erythropoiesis-Stimulating Agent) | Time to First Use of Rescue Therapy | Year 2 | 14.4 Percentage of participants |
| ESA (Erythropoiesis-Stimulating Agent) | Time to First Use of Rescue Therapy | Year 1.5 | 10.9 Percentage of participants |
| ESA (Erythropoiesis-Stimulating Agent) | Time to First Use of Rescue Therapy | Year 1 | 8.4 Percentage of participants |
| ESA (Erythropoiesis-Stimulating Agent) | Time to First Use of Rescue Therapy | Year 0.5 | 3.2 Percentage of participants |
Comparison: Hazard Ratio was calculated using stratified Cox Proportional Hazards regression stratifying on region, CV history, previous ESA treatment and adjusting on Hb at baseline as continuous covariate. Superiority was declared if the upper bound of the 95% CI was below 1.0.p-value: =0.91795% CI: [0.656, 1.462]Regression, Cox