Phase 3
N=836
Roxadustat in the Treatment of Anemia in End Stage Renal Disease (ESRD) Patients on Stable Dialysis
Anemia · End Stage Renal Disease (ESRD)
Bottom Line
View on ClinicalTrials.gov: NCT02278341 ↗Enrolled (actual)
836
Serious AEs
47.8%
Results posted
Aug 2020
Primary outcome: Primary: Change From Baseline (BL) to the Average Hemoglobin (Hb) in Weeks 28-36 Without Rescue Therapy [EU (EMA)] — 0.428; 0.193 g/dL — p=<0.001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Roxadustat (Drug); Epoetin alfa (Drug); Darbepoetin alfa (Drug); Iron (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Astellas Pharma Europe B.V.
- Primary completion
- Jun 2017
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline (BL) to the Average Hemoglobin (Hb) in Weeks 28-36 Without Rescue Therapy [EU (EMA)] |
0.428; 0.193 | <0.001 sig |
| PRIMARY Change From BL to the Average Hb in Weeks 28 to 52 Regardless of Rescue Therapy [US (FDA)] |
0.363; 0.192 | <0.001 sig |
| SECONDARY Percentage of Participants With Hb Response During Weeks 28 to 36 |
84.2; 82.4 | <0.05 sig |
| SECONDARY Change From BL in Low Density Lipoprotein Cholesterol (LDL-C) to the Average LDL-C of Weeks 12 to 28 |
-0.459; -0.082 | <0.001 sig |
| SECONDARY Mean Monthly Intravenous (IV) Iron Use |
21.6; 53.5 | <0.001 sig |
| 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 |
0.050; -0.155 | <0.05 sig |
| SECONDARY Change From BL in SF-36 Vitality (VT) Sub-score to the Average of Weeks 12 to 28 |
0.460; -0.396 | <0.05 sig |
| SECONDARY Change From BL in Mean Arterial Pressure (MAP) to the Average of Weeks 20 to 28 |
-0.969; -0.120 | <0.05 sig |
| SECONDARY Time to First Occurrence of an Increase in Blood Pressure |
11.6; 12.0; 16.1; 16.2; 21.2; 24.1 | =0.582 |
| SECONDARY Change From BL in Mean Arterial Pressure (MAP) to the Average MAP Value of Weeks 20 to 28 |
-0.739; -0.160 | =0.308 |
| SECONDARY Time to First Occurrence of an Increase in Blood Pressure |
11.6; 12.0; 16.1; 16.2; 21.2; 24.1 | =0.582 |
| SECONDARY Percentage of Participants With a Hb Response During Weeks 28 and 36 Regardless of Use of Rescue Therapy |
83.1; 82.1 | =0.609 |
| SECONDARY Change From BL in Hb to Each Postdosing Time Point |
0.232; 0.068; 0.496; 0.054; 0.633; 0.071 | <0.001 sig |
| SECONDARY Hb Level Averaged Over Weeks 28 to 36, 44 to 52, and 96 to 104 Without Use of Rescue Therapy |
11.183; 10.946; 11.099; 10.994; 11.007; 10.858 | <0.001 sig |
| 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 |
0.408; 0.173; 0.298; 0.194; 0.225; 0.076 | <0.001 sig |
| 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 |
93.002; 87.286; 89.421; 86.914; 88.858; 83.543 | — |
| 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 |
76.326; 76.098; 75.891; 74.634; 76.522; 73.690 | — |
| SECONDARY Number of Hospitalizations |
0.9; 0.9 | — |
| SECONDARY Number of Days of Hospitalization Per Year |
12.186; 7.868 | — |
| SECONDARY Time to First Hospitalization |
19.4; 18.3; 32.0; 32.7; 43.5; 41.9 | =0.164 |
| SECONDARY Time to First Use of Rescue Therapy |
3.9; 3.2; 8.2; 8.4; 11.4; 10.9 | =0.917 |
| SECONDARY Time to First RBC Transfusion |
3.6; 3.2; 7.4; 8.4; 10.0; 10.9 | =0.501 |
| SECONDARY Mean Monthly Number of RBC Packs Per Participant |
0.026; 0.032 | =0.507 |
| SECONDARY Mean Monthly Volume of RBC Transfusion Per Participant |
6.061; 5.929 | =0.949 |
| SECONDARY Time to First Use of IV Iron Supplementation |
11.2; 33.5; 17.4; 44.1; 23.6; 55.0 | <0.001 sig |
| SECONDARY Mean Monthly Intravenous (IV) Iron Per Participant During Weeks 37-52 and Weeks 53-104 |
34.9; 70.0; 49.5; 98.1 | <0.001 sig |
| SECONDARY Percentage of Participants With Oral Iron Use Only |
31.0; 11.7 | — |
| SECONDARY Change From BL to Each Post-dosing Study Visit in Total Cholesterol |
-0.608; -0.105; -0.641; -0.135; -0.803; -0.241 | — |
| SECONDARY Change From BL to Each Post-dosing Study Visit in LDL-C/High-density Lipoprotein Cholesterol (HDL-C) Ratio |
-0.245; -0.060; -0.155; -0.057; -0.345; -0.078 | — |
| SECONDARY Change From BL to Each Postdosing Study Visit in Non-HDL Cholesterol |
-0.518; -0.107; -0.540; -0.127; -0.700; -0.229 | — |
| SECONDARY Change From BL to Each Postdosing Study Visit in Apolipoproteins A1 (ApoA1) |
-0.114; -0.006; -0.113; -0.012; -0.097; -0.013 | — |
| SECONDARY Change From BL to Each Postdosing Study Visit in Apolipoproteins B (ApoB) |
-11.03; 1.00; -11.18; -0.12; -13.18; -0.01 | — |
| SECONDARY Change From BL to Each Postdosing Study Visit in ApoB/ApoA1 Ratio |
-0.037; 0.013; -0.034; 0.002; -0.051; 0.007 | — |
| SECONDARY Number of Participants With Mean LDL Cholesterol < 100 mg/dL Over Weeks 12 to 28 |
275; 231; 119; 181; 19; 8 | — |
| SECONDARY Number of Participants With CKD Who Achieved Antihypertensive Treatment Goal |
264; 261; 130; 149; 19; 10 | — |
| SECONDARY Change From BL to the Average of Weeks 12 to 28 in SF-36 Physical Component Score (PCS) |
0.560; 0.039 | =0.161 |
| 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 |
0.400; 0.274 | =0.845 |
| SECONDARY Change From BL to the Average Value of Weeks 12 to 28 in Total FACT-An Score |
-0.501; -0.373 | =0.922 |
| 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 |
3.041; 2.735 | — |
| SECONDARY Percentage of Participants With Improvements Measured by Patients' Global Impression of Change (PGIC) |
59.6; 49.5; 65.5; 49.5; 62.3; 57.1 | — |
| SECONDARY Change From BL in Serum Hepcidin |
-14.265; -4.265; -12.298; -6.741; -15.149; -11.818 | — |
| SECONDARY Change From BL in Serum Ferritin |
-214.64; -141.78; -245.37; -160.75; -269.76; -179.47 | — |
| SECONDARY Change From BL in Transferrin Saturation (TSAT) |
-4.151; -2.331; -3.681; -3.128; -2.643; -3.189 | — |
| 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) |
0.0009; -0.0005; -0.0004; -0.0006; -0.0001; -0.0004 | — |
| SECONDARY Number of Participants With Treatment-Emergent Adverse Events (TEAEs) |
359; 361; 77; 35; 210; 189 | — |
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.
Eligibility Criteria
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.
Data sourced from ClinicalTrials.gov (NCT02278341). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.