Phase 3
N=594
Roxadustat in the Treatment of Anemia in Chronic Kidney Disease Patients Not Requiring Dialysis
Anemia in Chronic Kidney Disease in Non-dialysis Patients
Bottom Line
View on ClinicalTrials.gov: NCT01887600 ↗Enrolled (actual)
594
Serious AEs
59.9%
Results posted
Dec 2020
Primary outcome: Primary: Percentage of Participants With a Hemoglobin (Hb) Response to Treatment at Two Consecutive Visits During the First 24 Weeks of Treatment Without Rescue Therapy Prior to Hb Response — 79.2; 9.9 Percentage of Participants — p=<0.001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Roxadustat (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Astellas Pharma Europe B.V.
- Primary completion
- Nov 2017
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With a Hemoglobin (Hb) Response to Treatment at Two Consecutive Visits During the First 24 Weeks of Treatment Without Rescue Therapy Prior to Hb Response |
79.2; 9.9 | <0.001 sig |
| PRIMARY Hb Change From Baseline (BL) to the Average Hb in Weeks 28-52 Regardless of Rescue Therapy |
1.992; 0.300 | <0.001 sig |
| SECONDARY Hb Change From BL to the Average Hb in Weeks 28-36 Without Having Received Rescue Therapy Within 6 Weeks Prior to and During 8-Week Evaluation Period |
2.069; 0.470 | <0.001 sig |
| SECONDARY Change From BL in Low-Density Lipoprotein (LDL) Cholesterol (Regardless of Fasting Status) to the Average LDL Cholesterol of Weeks 12 to 28 |
-0.650; 0.051 | <0.001 sig |
| SECONDARY Time to First Use of Rescue Therapy (Composite of Red Blood Cell (RBC) Transfusions, Erythropoiesis-stimulating Agent (ESA) Use, and Intravenous (IV) Iron) |
6.1; 33.3; 13.0; 50.1; 22.0; 52.5 | <0.001 sig |
| SECONDARY Change From BL in Short Form (SF)-36 Vitality (VT) Sub-score to the Average VT Sub-score of Weeks 12 to 28 |
2.788; 1.661 | =0.093 |
| SECONDARY Change From BL in SF-36 Physical Functioning (PF) Sub-score to the Average PF Sub-score of Weeks 12 to 28 |
1.344; 0.632 | =0.27 |
| SECONDARY Change From BL in Mean Arterial Pressure (MAP) to the Average MAP of Weeks 20 to 28 |
-0.814; -1.656 | =0.182 |
| SECONDARY Time to First Occurrence of Hypertension |
11.4; 10.1; 14.8; 12.5; 17.5; 12.5 | =0.334 |
| SECONDARY Rate of Progression of CKD Measured by Annualized Estimated Glomerular Filtration Rate (eGFR) Slope Over Time |
-2.65; -3.24 | =0.316 |
| SECONDARY Average Level of Hb Over Weeks 28 to 36 Without Use of Rescue Therapy Within 6 Weeks Prior to and During the Evaluation Period |
11.106; 9.468 | <0.001 sig |
| SECONDARY Average Level of Hb Over Weeks 44 to 52 Without Use of Rescue Therapy Within 6 Weeks Prior to and During the Evaluation Period |
10.984; 9.381 | <0.001 sig |
| SECONDARY Average Level of Hb Over Weeks 96 to 104 Without Use of Rescue Therapy Within 6 Weeks Prior to and During the Evaluation Period |
10.816; 9.324 | <0.001 sig |
| SECONDARY Time to Achieve the First Hb Response Without Rescue Therapy, as Defined by Primary Endpoint |
26.0; 3.5; 59.8; 6.2; 83.4; 9.4 | <0.001 sig |
| SECONDARY Hb Change From BL to Each Post-Dosing Time Point |
0.390; -0.006; 0.977; 0.039; 1.591; 0.119 | <0.001 sig |
| SECONDARY Hb Change From BL to the Average Hb Value of Weeks 28-36 Regardless of the Use of Rescue Therapy |
2.013; 0.399 | <0.001 sig |
| SECONDARY Hb Change From BL to the Average Hb Value of Weeks 44-52 Regardless of the Use of Rescue Therapy |
1.886; 0.292 | <0.001 sig |
| SECONDARY Hb Change From BL to the Average Hb Value of Weeks 96-104 Regardless of the Use of Rescue Therapy |
1.779; 0.327 | <0.001 sig |
| SECONDARY Percentage of Hb Values Within 10.0-12.0 g/dL in Weeks 28-36 Without Use of Rescue Therapy |
64.18; 34.20 | — |
| SECONDARY Percentage of Hb Values Within 10.0-12.0 g/dL in Weeks 44-52 Without Use of Rescue Therapy |
69.39; 35.45 | — |
| SECONDARY Percentage of Hb Values Within 10.0-12.0 g/dL in Weeks 96-104 Without Use of Rescue Therapy |
64.65; 40.63 | — |
| SECONDARY Time to First Hospitalization |
32.2; 39.8; 49.9; 49.3; 62.1; 64.0 | =0.643 |
| SECONDARY Number of Days of Hospitalization Per Patient Exposure Year (PEY) |
14.567; 15.885 | — |
| SECONDARY Time to First Use of Rescue Therapy (Composite of RBC, Transfusions, ESA Use, and IV Iron) in the First 24 Weeks of Treatment |
0.8; 6.0; 2.5; 15.8; 3.3; 25.3 | <0.001 sig |
| SECONDARY Time to First Use of RBC Transfusions |
2.9; 15.2; 5.6; 20.2; 12.1; 21.8 | <0.001 sig |
| SECONDARY Mean Monthly Number of RBC Packs |
0.041; 0.089 | =0.128 |
| SECONDARY Mean Monthly Volume of Blood Transfused |
11.331; 22.596 | =0.183 |
| SECONDARY Time to First Use of ESA Rescue Therapy |
1.8; 20.4; 4.8; 36.4; 6.0; 42.3 | <0.001 sig |
| SECONDARY Time to First Use of IV Iron |
2.3; 6.2; 5.3; 9.4; 7.5; 10.7 | =0.045 sig |
| SECONDARY Change From BL to Each Post-Dosing Visit in Total Cholesterol |
-1.151; 0.108; -1.066; 0.048; -0.836; 0.088 | — |
| SECONDARY Change From BL to Each Post-Dosing Visit in Low Density Lipoprotein (LDL)/High-Density Lipoprotein (HDL) Ratio |
-0.331; 0.076; -0.374; 0.068; -0.268; 0.081 | — |
| SECONDARY Change From BL to Each Post-Dosing Visit in Non-HDL Cholesterol |
-0.969; 0.118; -0.909; 0.070; -0.709; 0.078 | — |
| SECONDARY Change From BL to Each Post-Dosing Visit in Apolipoproteins A1 (ApoA1) |
-0.168; 0.013; -0.148; 0.008; -0.131; 0.004 | — |
| SECONDARY Change From BL to Each Post-Dosing Visit in Apolipoproteins B (ApoB) |
-19.891; 2.059; -19.483; 2.059; -14.935; 0.278 | — |
| SECONDARY Change From BL to Each Post-Dosing Visit in Ratio ApoB/ApoA1 |
-0.073; 0.010; -0.084; 0.000; -0.059; -0.006 | — |
| SECONDARY Percentage of Participants With Mean LDL Cholesterol <100 mg/dL Calculated Over Weeks 12 to 28 |
62.9; 41.1; 37.1; 58.9 | — |
| SECONDARY Percentage of Participants Who Have Achieved Antihypertensive Treatment Goal in CKD Participants Over Weeks 12-28 |
25.6; 28.0; 74.4; 72.0 | — |
| SECONDARY Change From BL to the Average Value of Weeks 12-28 in Quality of Life (QoL) SF-36 Physical Component Score (PCS) |
1.842; 1.468 | =0.475 |
| SECONDARY Change From BL to the Average Value of Weeks 12-28 in Anemia Subscale (Ans) of Functional Assessment of Cancer Therapy (FACT-An) Score |
4.470; 2.766 | =0.047 sig |
| SECONDARY Change From BL to the Average Value of Weeks 12-28 in Total FACT-An Score |
5.777; 3.691 | =0.225 |
| SECONDARY Change From BL to the Average Value of Weeks 12-28 in the Euroqol Questionnaire - 5 Dimensions 5 Levels (EQ-5D 5L) Visual Analogue Scale (VAS) Score |
5.390; 0.990 | — |
| SECONDARY Change From BL to the Average Value of Weeks 12-28 in Overall Work Impairment Due to Anaemic Symptoms |
-5.965; -4.230 | — |
| SECONDARY Percentage of Participants in Each Category in Patients' Global Impression of Change (PGIC) |
41.2; 18.9; 46.4; 28.6 | — |
| SECONDARY Change From BL to Each Study Visit in Serum Hepcidin |
-19.835; 1.748; -17.369; 0.971; -10.684; -1.879 | — |
| SECONDARY Change From BL to Each Study Visit in Serum Ferritin |
-221.827; 11.564; -247.955; 1.789; -265.812; -21.098 | — |
| SECONDARY Change From BL to Each Study Visit in Serum Transferrin Saturation (TSAT) |
-7.4; 0.7; -5.7; -0.4; -4.6; -0.7 | — |
| SECONDARY Change From BL to Each Study Visit in Serum HbA1c Level |
0.0007; -0.0001; 0.0006; 0.0008; 0.0011; 0.0007 | — |
| SECONDARY Change From BL to Each Study Visit in Fasting Blood Glucose |
0.107; -0.076; -0.103; -0.162; -0.100; -0.153 | — |
| SECONDARY Change From BL to Each Study Visit in Albumin/Creatinine Ratio in Urine |
1.08; 1.06; 1.19; 1.16; 1.21; 1.04 | — |
| SECONDARY Change From BL to Each Study Visit in Serum Creatinine (Cr) Ratio |
1.01; 1.05; 1.03; 1.07; 1.04; 1.07 | — |
| SECONDARY Time to Doubling of Serum Creatinine or Chronic Dialysis or Renal Transplant Compared to Baseline |
17.4; 17.8; 36.8; 35.4; 47.3; 48.2 | =0.973 |
| SECONDARY Time to CKD Progression (Composite of Doubling Serum Creatinine, Chronic Dialysis or Renal Transplant, and Death) |
20.5; 20.0; 40.3; 38.3; 50.2; 50.5 | =0.972 |
| SECONDARY Time to at Least 40% Decrease in eGFR From Baseline, Chronic Dialysis or Renal Transplant |
20.7; 22.3; 44.4; 44.0; 54.6; 62.8 | =0.439 |
Summary
This study was conducted to treat anemia in patients with chronic kidney disease. Anemia is a reduced number of red blood cells or hemoglobin. Hemoglobin is important for the transport of oxygen in your blood. The purpose of the study was to see if Roxadustat is both effective and safe as a treatment for anemia in patients with chronic kidney disease.
Eligibility Criteria
Inclusion criteria
- Participant has a diagnosis of chronic kidney disease, with Kidney Disease Outcomes Quality Initiative (KDOQI) Stage 3, 4 or 5, not receiving dialysis; with an Estimated Glomerular Filtration Rate (eGFR) ULN, and/or fever, in conjunction with clinical signs or symptoms of infection within one week prior to randomization.
- Participant has a known untreated proliferative diabetic retinopathy, diabetic macular edema, macular degeneration and retinal vein occlusion.
- Participant has had any prior organ transplant (that has not been explanted) or a scheduled organ transplantation.
- Participant has participated in any interventional clinical study or has been treated with any investigational drugs within 30 days or 5 half lives or limit set by national law, whichever is longer, prior to the initiation of Screening.
- Participant 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.
- Participant has a history of alcohol or drug abuse within 2 years prior to randomization.
Data sourced from ClinicalTrials.gov (NCT01887600). 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.