Phase 3
N=616
Roxadustat in the Treatment of Anemia in Chronic Kidney Disease (CKD) Patients, Not on Dialysis, in Comparison to Darbepoetin Alfa
Anemia in Chronic Kidney Disease in Non-dialysis Patients
Bottom Line
View on ClinicalTrials.gov: NCT02021318 ↗Enrolled (actual)
616
Serious AEs
63.3%
Results posted
Mar 2021
Primary outcome: Primary: Percentage of Participants With a Hb Response to Treatment at Two Consecutive Visits During the First 24 Weeks of Treatment Without Rescue Therapy — 89.5; 78.0 Percentage of Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Roxadustat (Drug); Darbepoetin alfa (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Astellas Pharma Europe B.V.
- Primary completion
- Mar 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With a Hb Response to Treatment at Two Consecutive Visits During the First 24 Weeks of Treatment Without Rescue Therapy |
89.5; 78.0 | — |
| SECONDARY Change From Baseline in Hb to the Average Hb of Weeks 28 to 36 Without Rescue Therapy Within 6 Weeks Prior to and During This 8-Week Evaluation Period |
1.848; 1.839 | 0.839 |
| SECONDARY Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) to the Average LDL-C of Weeks 12 to 28 |
-0.352; 0.049 | <0.001 sig |
| SECONDARY Time to First Intravenous Iron Use |
0; 2.8; 1.3; 6.7; 3.3; 9.2 | 0.004 sig |
| SECONDARY Change From Baseline in Short Form-36 (SF-36) Physical Functioning (PF) Sub-Score to the Average PF Sub Score in Weeks 12 to 28 |
0.913; 2.062 | 0.027 sig |
| SECONDARY Change From Baseline in SF-36 Vitality (VT) Sub-Score to the Average VT Sub-Score in Weeks 12 to 28 |
4.077; 3.881 | 0.454 |
| SECONDARY Change From Baseline in Mean Arterial Pressure (MAP) to the Average MAP Value in Weeks 20 to 28: Per Protocol Set |
0.541; 0.588 | 0.547 |
| SECONDARY Time to First Occurrence of Hypertension During Weeks 1 to 36: Per Protocol Set |
17.5; 19.4 | 0.336 |
| SECONDARY Change From Baseline in MAP to the Average MAP Value in Weeks 20 to 28: Full Analysis Set |
0.635; 0.457 | 0.818 |
| SECONDARY Time to First Occurrence of Hypertension During Weeks 1 to 36: Full Analysis Set |
17.4; 18.8 | 0.452 |
| SECONDARY Change From Baseline in Hb to the Average Hb Value of Weeks 28 to 52 Regardless of Rescue Therapy |
1.718; 1.673 | 0.529 |
| SECONDARY Time to First Hb Response During First 24 Weeks of Treatment Regardless of Administration of Rescue Therapy |
88.8; 77.7 | <0.001 sig |
| SECONDARY Time to First Hb Response During First 24 Weeks of Treatment Without Rescue Therapy |
88.2; 77.4 | <0.001 sig |
| SECONDARY Hb Level Averaged Over Weeks 28 to 36, 44 to 52, 72 to 80 and 96 to 104 Without Rescue Therapy |
11.403; 11.351; 11.185; 11.188; 11.225; 11.217 | 0.478 |
| SECONDARY Change From Baseline in Hb to Each Postdosing Time Point Regardless Use of Rescue Therapy |
0.381; 0.294; 0.862; 0.584; 1.508; 1.073 | 0.086 |
| SECONDARY Change From Baseline in Hb to Average Hb Value of Weeks 28 to 36, 44 to 52, 72 to 80, 96 to 104 Regardless of Use of Rescue Therapy |
1.825; 1.799; 1.619; 1.62; 1.652; 1.649 | 0.727 |
| SECONDARY Percentage of Hb Values >=10 g/dL and 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 |
93.078; 92.481; 67.896; 69.217; 90.921; 89.416 | — |
| SECONDARY Time to First Hb Rate of Rise > 2 g/dL Within 4 Weeks |
45.5; 28.9; 48.8; 30.9; 53.4; 35 | <0.001 sig |
| SECONDARY Number of Hospitalizations |
1.5; 1.4 | — |
| SECONDARY Number of Days of Hospitalization Per Year |
12.6; 11.3 | — |
| SECONDARY Time to First Hospitalization |
31.7; 21.8; 43.7; 40.4; 55.2; 50.2 | 0.079 |
| SECONDARY Time to First Use of RBC Transfusion |
3; 2.1; 7.3; 6.5; 10.9; 9.4 | 0.300 |
| SECONDARY Number of RBC Packs |
0.4; 0.4 | — |
| SECONDARY Volume of RBC Transfused |
97.0; 334.63 | — |
| SECONDARY Number of Particpants Who Received RBC Transfusions |
38; 28 | — |
| SECONDARY Time to First Use of Rescue Therapy |
4; 2.1; 9.3; 6.5; 13.3; 9.4 | 0.055 |
| SECONDARY Number of Participants Who Received Rescue Therapy (Composite of RBC Transfusions (All Participants) and Darbepoetin Alfa Use (Roxadustat Treated Participants Only) |
46; 28 | — |
| SECONDARY Mean Monthly Intravenous Iron Per Participant During Weeks 37 to 52 and 53 to 104 |
11.028; 13.208; 18.702; 31.315 | — |
| SECONDARY Time to First Use of IV Iron Supplementation |
4.3; 11.8; 10; 19.2; 15.9; 24.2 | 0.052 |
| SECONDARY Percentage of Participants With Oral Iron Use Only |
50.6; 52.7; 55.3; 55.1; 55.6; 55.4 | — |
| SECONDARY Change From Baseline to Weeks 8, 28, 52 and 104 in Total Cholesterol |
-0.92; -0.046; -0.531; 0.016; -0.524; -0.111 | — |
| SECONDARY Change From Baseline to Weeks 8, 28, 52 and 104 in LDL-C/High-Density Lipoprotein Cholesterol (HDL-C) Ratio |
-0.209; -0.049; 0.016; 0.053; 0.014; -0.065 | — |
| SECONDARY Change From Baseline to Weeks 8, 28, 52 and 104 in Non-HDL Cholesterol |
-0.729; -0.045; -0.392; 0.02; -0.383; -0.114 | — |
| SECONDARY Change From Baseline to Weeks 8, 28, 52 and 104 in Apolipoproteins A1 (ApoA1) |
-0.184; 0.026; -0.104; 0.055; -0.12; 0.027 | — |
| SECONDARY Change From Baseline to Weeks 8, 28, 52 and 104 in Apolipoproteins B (ApoB) |
-16.5; -0.71; -10.659; 0.091; -10.74; -3.539 | — |
| SECONDARY Change From Baseline to Weeks 8, 28, 52 and 104 in ApoB/ApoA1 Ratio |
-0.031; -0.019; -0.026; -0.034; -0.025; -0.038 | — |
| SECONDARY Number of Participants With Mean LDL Cholesterol < 100 mg/dL |
147; 111; 20; 33; 10; 8 | — |
| SECONDARY Number of Participants Who Had Achieved Antihypertensive Treatment Goal |
76; 64; 228; 212; 18; 16 | — |
| SECONDARY Change From Baseline to the Average of Weeks 12 to 28 and 36 to 52 in SF-36 Physical Component Score (PCS) |
1.222; 2.29; 1.083; 1.686 | 0.027 sig |
| SECONDARY Change From Baseline to the Average of Weeks 12 to 28 and 36 to 52 in Anemia Subscale (AnS) (Additional Concerns) of Functional Assessment of Cancer Therapy-Anemia (FACT-An) Score |
4.71; 5.238; 3.661; 4.608 | 0.517 |
| SECONDARY Change From Baseline to the Average Value of Weeks 12 to 28 and 36 to 52 in FACT-An Total Score |
7.761; 8.665; 5.492; 7.259 | 0.570 |
| SECONDARY Change From Baseline to the Average Value of Weeks 12 to 28 and 36 to 52 in FACT-An Trial Outcome Index (TOI) Score |
6.798; 6.876; 5.602; 5.595 | — |
| SECONDARY Change From Baseline to the Average Value of Weeks 12 to 28 in Euroqol Questionnaire-5 Dimensions 5 Levels (EQ-5D 5L) Visual Analogue Scale (VAS) Score |
5.137; 4.353 | 0.497 |
| SECONDARY Change From Baseline to the Average Value of Weeks 12 to 28 and 36 to 52 in Work Productivity and Activity Impairment-Anemic Symptoms (WPAI:ANS) Score: Percent Work Time Missed |
-3.793; 0.842; -0.078; 0.216 | — |
| SECONDARY Change From Baseline to the Average Value of Weeks 12 to 28 and 36 to 52 in WPAI:ANS Score: Percent Impairment While Working |
-6.618; -2.433; -7.879; 1.083 | — |
| SECONDARY Change From Baseline to the Average Value of Weeks 12 to 28 and 36 to 52 in WPAI:ANS Score: Percent Overall Work Impairment |
-6.112; -1.217; 2.817; 0.197 | — |
| SECONDARY Change From Baseline to the Average Value of Weeks 12 to 28 and 36 to 52 in WPAI:ANS Score: Percent Activity Impairment |
-9.581; -9.34; -9.365; -8.17 | — |
| SECONDARY Percentage of Participants With Improvements Measured by Patients' Global Impression of Change (PGIC) |
76.1; 79.4; 83.7; 83.6; 83; 81 | — |
| SECONDARY Change From Baseline to Each Scheduled Measurement in Serum Ferritin |
-190.762; -159.174; -229.471; -208.356; -205.722; -201.587 | — |
| SECONDARY Change From Baseline to Each Scheduled Measurement in Transferrin Saturation (TSAT) |
-6; -2.1; -5.9; -2.4; -2.4; -0.5 | — |
| SECONDARY Change From Baseline to Each Scheduled Measurement in Glycated Hemoglobin (HbA1c) |
0.0021; 0.001; 0.0009; 0.0015; 0.0021; 0.0021 | — |
| SECONDARY Change From Baseline to Each Scheduled Measurement in Fasting Blood Glucose |
7; 10.3; 4.1; 1.3; 9.3; 7.1 | — |
| SECONDARY Change From Baseline to Each Scheduled Measurement in Estimated Glomerular Filtration Rate (eGFR) |
1.01; 0.97; 1.01; 0.96; 1.02; 0.95 | — |
| SECONDARY Rate of Progression of Chronic Kidney Disease Measured by eGFR Slope Over Time |
-2.95; -2.89 | 0.902 |
| SECONDARY Change From Baseline to Each Scheduled Measurement in Urine Albumin/Creatinine Ratio (UACR) |
1.19; 1.23; 1.18; 1.22; 1.22; 1.18 | — |
| SECONDARY Time to Doubling of Serum Creatinine or Chronic Dialysis or Renal Transplant Compared to Baseline |
12.9; 8.6; 27.4; 27.2; 38.2; 38.8 | 0.960 |
| SECONDARY Number of Participants With End Stage Renal Disease (ESRD) |
110; 107 | — |
| SECONDARY Time to Chronic Kidney Disease Progression (Composite of Doubling Serum Creatinine, Chronic Dialysis or Renal Transplant, and Death) |
14; 10.2; 30.9; 29.5; 42.1; 42.6 | 0.939 |
| SECONDARY Time to Chronic Dialysis or Renal Transplant or Death |
12.7; 9.2; 27.1; 26.2; 37.1; 37.7 | 0.948 |
| SECONDARY Time to at Least 40% Decrease in eGFR From Baseline, Chronic Dialysis or Renal Transplant |
15.4; 13; 34.5; 35.5; 47.2; 50.2 | 0.568 |
| SECONDARY Number of Participants With Treatment Emergent Adverse Events (TEAEs) |
296; 271; 78; 66; 209; 181 | — |
Summary
The primary objective of this study was to evaluate the efficacy of roxadustat compared to darbepoetin alfa in the treatment of anemia in nondialysis-dependent chronic kidney disease (NDD CKD) participants.
Eligibility Criteria
Inclusion Criteria
- Subject has a diagnosis of CKD, with Kidney Disease Outcomes Quality Initiative (KDOQI) Stage 3, 4 or 5, not on dialysis; with an Estimated Glomerular Filtration Rate (eGFR) Upper Limit of Normal (ULN), and/or fever, in conjunction with clinical signs or symptoms of infection within one week prior to randomization.
- Subject has a known untreated proliferative diabetic retinopathy, diabetic macular edema, macular degeneration or retinal vein occlusion.
- Subject has had any prior organ transplant (that has not been explanted), subject is scheduled for organ transplantation, or subject is likely to initiate renal replacement therapy including dialysis within the first year of the study.
- Subject will be excluded from participation if any of the following apply:
- subject has received investigational therapy within 30 days or 5 half lives or limit set by national law, whichever is longer, prior to initiation of screening, or
- any condition which makes the subject unsuitable for study participation.
- Subject has an anticipated use of dapsone in any dose amount or chronic use of acetaminophen/paracetamol >2.0 g/day during the treatment or follow-up period of the study.
- Subject has a history of alcohol or drug abuse within 2 years prior to randomization
Data sourced from ClinicalTrials.gov (NCT02021318). 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.