Phase 3
N=1,043
Safety and Efficacy Study of Roxadustat (FG-4592) for the Treatment of Anemia in End-Stage Renal Disease (ESRD) Newly Initiated Dialysis Participants
Anemia in Incident Dialysis Patients
Bottom Line
View on ClinicalTrials.gov: NCT02052310 ↗Enrolled (actual)
1,043
Serious AEs
43.5%
Results posted
Oct 2021
Primary outcome: Primary: US (FDA) Submission: Mean Hb Change From Baseline to The Average Level During The Evaluation Period (Week 28 to Week 52), Regardless of Rescue Therapy (ITT Population) — 8.43; 8.46; 2.57; 2.36 g/dL — p=0.0005
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Roxadustat (Drug); Epoetin Alfa (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Kyntra Bio
- Primary completion
- Sep 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY US (FDA) Submission: Mean Hb Change From Baseline to The Average Level During The Evaluation Period (Week 28 to Week 52), Regardless of Rescue Therapy (ITT Population) |
8.43; 8.46; 2.57; 2.36 | 0.0005 sig |
| PRIMARY Ex-U.S. Submission: Hb Responder Rate- Percentage of Participants Who Achieved a Hb Response at 2 Consecutive Visits at Least 5 Days Apart During First 24 Weeks of Treatment, Without Rescue Therapy Within 6 Weeks Prior to the Hb Response (PPS Population) |
88.2; 84.4 | — |
| SECONDARY US (FDA Submission): Hb Responder Rate- Percentage of Participants Who Achieved a Hb Response at 2 Consecutive Visits at Least 5 Days Apart During First 24 Weeks of Treatment, Without Rescue Therapy Within 6 Weeks Prior to the Hb Response (ITT Population) |
84.3; 79.5 | — |
| SECONDARY Ex-US Submission: Mean Hb Change From Baseline to The Average Level During The Evaluation Period (Week 28 to Week 52), Regardless of Rescue Therapy (PPS Population) |
8.43; 8.43; 2.62; 2.44 | 0.0148 sig |
| SECONDARY Mean Change From Baseline in Low-Density Lipoprotein (LDL) Cholesterol Averaged Over Weeks 12 to 24 |
109.12; 109.22; -23.80; -5.39 | <0.0001 sig |
| SECONDARY Mean Change From Baseline in Hb Levels Between Weeks 18 to 24 Regardless of Rescue Therapy in Participants Whose Baseline High Sensitivity C-Reactive Protein (Hs-CRP)> Upper Limit of Normal (ULN) |
8.54; 8.38; 2.34; 2.48 | 0.8178 |
| SECONDARY Median Monthly IV Iron Use Per Patient-Exposure-Month (PEM) During Weeks 28 to 52 |
0.00; 26.86 | 0.00028 sig |
| SECONDARY Time to First RBC Transfusion |
NA; NA | 0.3284 |
| SECONDARY Mean Change From Baseline in Mean Arterial Pressure (MAP) Averaged Over Weeks 8 to 12 |
99.33; 99.04; -0.12; 1.15 | — |
| SECONDARY Time to First Exacerbation of Hypertension During Weeks 28 to 52 |
NA; NA | — |
| SECONDARY Percentage of Participants With Exacerbation of Hypertension During Weeks 28 to 52 |
14.0; 15.2 | — |
| SECONDARY Time to Achieve the First Hb Response up to Week 24 Censoring for Rescue Therapy |
7.1; 8.1 | — |
| SECONDARY Percentage of Participants With Hb ≥10.0 g/dL Averaged Over Weeks 28 to 36 and 28 to 52, Regardless of Rescue Therapy |
73.4; 70.8; 73.6; 72.5 | — |
| SECONDARY Mean Hb Change From Baseline to The Average Level During The Evaluation Period (Week 28 to Week 36), Censoring for Rescue Therapy |
2.70; 2.46 | — |
Summary
The purpose of this study is to determine whether roxadustat is safe and effective in the treatment of anemia in participants who have just begun dialysis treatment for ESRD.
Eligibility Criteria
Inclusion Criteria
- Participant has been informed of the investigational nature of this study and has given written informed consent in accordance with institutional, local, and national guidelines.
- Receiving HD or PD for ESRD for a minimum of 2 weeks and a maximum of 4 months, prior to randomization.
- Hemodialysis access consisting of an arteriovenous (AV) fistula, AV graft, or tunnelled (permanent) catheter; or PD catheter in use.
- Mean of the two most recent predialysis Hb values during the Screening Period, obtained at least 2 days apart, must be ≤ 10.0 g/dL, with a difference of ≤ 1.3 g/dL between the highest and the lowest values. The last Hb value must be drawn within 10 days prior to randomization.
- Ferritin ≥ 100 nanograms (ng)/milliliter (mL) (≥ 220 picomoles (pmol)/L); participants with ferritin level ULN, and/or fever, in conjunction with clinical signs or symptoms of infection at the time of randomization.
- History of chronic liver disease (for example, chronic infectious hepatitis, chronic auto-immune liver disease, cirrhosis, or fibrosis of the liver).
- New York Heart Association Class III or IV congestive heart failure at screening.
- Myocardial infarction, acute coronary syndrome, stroke, seizure, or a thromboembolic event within a major vessel (excluding vascular dialysis access) (for example, deep vein thrombosis or pulmonary embolism) within 12 weeks prior to randomization.
- Uncontrolled hypertension, in the opinion of the Investigator, (for example, that requires a change in anti-hypertensive medication) within 2 weeks prior to randomization.
- Renal imaging performed within 12 weeks prior to randomization indicative of a diagnosis or suspicion (for example, complex kidney cyst of Bosniak Category 2 or higher) of renal cell carcinoma.
- 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.
- Positive for any of the following: human immunodeficiency virus (HIV); hepatitis B surface antigen (HBsAg); or anti-hepatitis C virus antibody (anti-HCV Ab).
- Chronic inflammatory disease that could impact erythropoiesis (for example, systemic lupus erythematosus, rheumatoid arthritis, celiac disease) even if it is currently in remission.
- Known, untreated proliferative diabetic retinopathy, diabetic macular edema, macular degeneration, or retinal vein occlusion (participants who are already blind for the above reasons qualify to participate).
- Known history of myelodysplastic syndrome or multiple myeloma.
- 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).
- Known hemosiderosis, hemochromatosis, coagulation disorder, or a hypercoagulable condition.
- Organ transplant: participants with any of the following:
- Experienced rejection of a transplanted organ within 6 months of transplantation
- Currently on high doses of immunosuppressive therapy (per discretion of the Investigator)
- Scheduled for organ transplantation. Note: being on a waiting list for kidney transplant is not exclusionary
- Anticipated elective surgery, except for vascular access surgery or dialysis catheter placement, that is expected to lead to significant blood loss, or anticipated elective coronary revascularization.
- Active or chronic gastrointestinal bleeding.
- Any prior treatment with roxadustat or a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI).
- Use of iron-chelating agents within 4 weeks prior to randomization.
- Known hypersensitivity reaction to any ESA.
- Use of an investigational drug or treatment, participation in an investigational study, or presence of an expected carryover effect of an investigational treatment, within 4 weeks prior to randomization.
- Anticipated use of dapsone or androgens at any dose
Data sourced from ClinicalTrials.gov (NCT02052310). 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.