Anemia Associated With End Stage Renal Disease
Conditions
Brief summary
The purpose of this study is to assess the safety and effectiveness of roxadustat dosing regimens among hemodialysis participants converted from erythropoiesis stimulating agent (ESA) therapy or who are ESA-naïve.
Interventions
DRUGRoxadustat
Roxadustat will be administered per dose and schedule specified in the arm description.
Sponsors
AstraZeneca
FibroGen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Receiving chronic dialysis for end stage renal disease (ESRD) * Vascular access must be a functioning native arteriovenous fistula or graft with adequate flow in the opinion of the investigator, or permanent tunnelled catheter * Screening Hb criteria: Participants converting from an ESA: between 9.0 to 12.0 grams (g)/deciliter (dL); Participants initiating anemia treatment: \< 10.0 g/dL * Ferritin ≥ 50 nanograms (ng)/mililiter (mL), Transferrin saturation (TSAT) ≥ 10% at screening * 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 at screening and prior to initiating roxadustat treatment. * Body weight between 45.0 to 160.0 kg Key
Exclusion criteria
* Red blood cell (RBC) transfusion within 4 weeks prior to enrollment * Known history of myelodysplastic syndrome or multiple myeloma * Known hereditary hematologic disease or other known causes for anemia other than chronic kidney disease (CKD) * Known chronic inflammatory disease that is determined by the investigator to be the primary cause of anemia * Active or chronic gastrointestinal bleeding * Treated with iron-chelating agents within 4 weeks prior to enrollment * History of New York Heart Association (NYHA) Class III or IV congestive heart failure * History of myocardial infarction, acute coronary syndrome, stroke, seizure, or a thrombotic/thromboembolic event (excluding vascular dialysis access stenosis/thrombosis) within 12 weeks prior to enrollment * Uncontrolled hypertension, in the opinion of the Investigator * Participant has a diagnosis or suspicion (for example, complex kidney cyst of Bosniak Category II or higher) of renal cell carcinoma (Principal Investigator's discretion) * History of malignancy, except for cancers determined to be cured or in remission for ≥ 2 years, curatively resected basal cell or squamous cell skin cancers, cervical cancer in situ, or resected colonic polyps
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Mean Hb Value ≥10 g/dL | Week 16 through Week 24 | Percentage of participants with mean Hb value ≥10 g/dL, averaged from Week 16 through Week 24 has been reported. Baseline Hb was defined as the mean of available central laboratory Hb values prior to first dose of study medication including the predose Hb value collected on Day 1. 95% confidence interval (CI) was calculated based on the normal approximation to the binomial distribution. |
| Mean Hb Change From Baseline to Average Hb From Weeks 16-24 | Baseline, Weeks 16-24 | Baseline Hb was defined as the mean of available central laboratory Hb values prior to first dose of study medication including the predose Hb value collected on Day 1. Missing data was imputed using Monte Carlo Markov Chain (MCMC) imputation model. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Roxadustat Participants received roxadustat as an oral tablet, TIW for up to a maximum of 24 weeks. If a participant required roxadustat \<60 mg/week to maintain Hb levels, the dose frequency was reduced in a stepwise manner, for example, to BIW, and then QW. For participants converted from an ESA, the initial roxadustat dose was based on the average prescribed ESA dose in the last 4 weeks (for epoetin alfa and darbepoetin alfa) or 8 weeks (for Mircera®). For participants with \<6 weeks of prior ESA use, the initial roxadustat dose was based on a 2-tiered, weight-based dosing scheme. Dose adjustment evaluations were made every 4 weeks and doses were titrated based on Hb level and rate of Hb change. The prescribed dose did not exceed the maximum allowable dose of 3.0 mg/kg/dose or 400 mg per dose, whichever was lower. | 283 |
| Total | 283 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Death | 10 |
| Overall Study | Kidney Transplant | 7 |
| Overall Study | Other than specified | 4 |
| Overall Study | Participants continued an Optional Extension of Roxadustat Treatment | 216 |
| Overall Study | Transferred/Relocation | 5 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Roxadustat |
|---|---|
| Age, Continuous | 59.0 years STANDARD_DEVIATION 13.12 |
| Baseline Hb | 10.554 grams (g)/deciliter (dL) STANDARD_DEVIATION 0.7228 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 91 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 191 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 17 Participants |
| Race/Ethnicity, Customized Race Asian | 8 Participants |
| Race/Ethnicity, Customized Race Black or African American | 113 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Other Pacific Islander | 5 Participants |
| Race/Ethnicity, Customized Race Not Reported | 2 Participants |
| Race/Ethnicity, Customized Race Other | 7 Participants |
| Race/Ethnicity, Customized Race White | 131 Participants |
| Sex: Female, Male Female | 116 Participants |
| Sex: Female, Male Male | 167 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 11 / 283 |
| other Total, other adverse events | 19 / 283 |
| serious Total, serious adverse events | 82 / 283 |
Outcome results
Primary
Mean Hb Change From Baseline to Average Hb From Weeks 16-24
Baseline Hb was defined as the mean of available central laboratory Hb values prior to first dose of study medication including the predose Hb value collected on Day 1. Missing data was imputed using Monte Carlo Markov Chain (MCMC) imputation model.
Time frame: Baseline, Weeks 16-24
Population: The full analysis set included all enrolled participants who provided baseline Hb data and data for at least 1 postbaseline Hb time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Roxadustat | Mean Hb Change From Baseline to Average Hb From Weeks 16-24 | 0.22 g/dL | Standard Deviation 1.029 |
Primary
Percentage of Participants With Mean Hb Value ≥10 g/dL
Percentage of participants with mean Hb value ≥10 g/dL, averaged from Week 16 through Week 24 has been reported. Baseline Hb was defined as the mean of available central laboratory Hb values prior to first dose of study medication including the predose Hb value collected on Day 1. 95% confidence interval (CI) was calculated based on the normal approximation to the binomial distribution.
Time frame: Week 16 through Week 24
Population: The full analysis set included all enrolled participants who provided baseline Hb data and data for at least 1 postbaseline Hb time point.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Roxadustat | Percentage of Participants With Mean Hb Value ≥10 g/dL | 83.7 percentage of participants |