Anemia, Chronic Kidney Disease, End Stage Renal Disease
Conditions
Keywords
Kidney, ESRD, End Stage Renal Disease, Anemia, Oral anemia treatment, Hemoglobin levels, Hemodialysis, CKD, Chronic Kidney Disease, Peritoneal, HD, PD, Hb, Erythropoietin, Blood count
Brief summary
The purpose of this open-label extension study is to evaluate long-term efficacy and safety of roxadustat in maintaining hemoglobin (Hb) in participants with dialysis and non-dialysis chronic kidney disease (CKD) who have completed the Treatment Period of a roxadustat FibroGen-sponsored anemia study.
Detailed description
This is an open-label, long-term maintenance study of roxadustat anemia therapy in participants with dialysis and non-dialysis CKD who have completed the Treatment Period of a roxadustat FibroGen-sponsored anemia study. Participants assigned to roxadustat in the previous study will continue to receive the same roxadustat dose and dosing frequency, unless a dose adjustment is required.
Interventions
DRUGRoxadustat
Oral capsule
Sponsors
AstraZeneca
Astellas Pharma Inc
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
1. Minimum age 18 years 2. Completed the Treatment Period of an ongoing roxadustat FibroGen-sponsored anemia study in the United States.
Exclusion criteria
1. Participants assigned to epoetin alfa in a previous ongoing roxadustat anemia study 2. Pregnant or breastfeeding females 3. Females of childbearing potential, unless using adequate contraception; male participants with sexual partners of childbearing potential who are not on birth control unless the male participant agrees to use adequate contraception 4. Participants who received roxadustat in a previous study that did not demonstrate adequate hemoglobin response per the investigator's clinical judgment 5. Any medical condition that in the opinion of the investigator may pose a safety risk to a participant in this study or which may interfere with study participation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hb Over Time | Baseline, Weeks 8, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 252, 264, 288, 312, 336, 360, and 384 | Hb baseline was defined as the mean of the central laboratory Hb value from the baseline visit at Day 1 (prior to receiving the first dose of study drug in this study), plus any other central lab Hb values within 15 days prior to Day 1 regardless of fasting. The specific duration over which the participants were assessed was identified as over time for the endpoint in the study protocol. Therefore, to be consistent with the endpoint in the study protocol, an individual timepoint was not identified for this primary outcome measure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Hb ≥10 g/dL | Baseline up to Week 384 | Hb baseline was defined as the mean of the central laboratory Hb value from the baseline visit at Day 1 (prior to receiving the first dose of study drug in this study), plus any other central lab Hb values within 15 days prior to Day 1 regardless of fasting. |
| Number of Participants Receiving Rescue Therapy (Composite of Blood Transfusions, Intravenous [IV] Iron, Erythropoiesis-Stimulating Agent [ESA]) | Baseline up to Week 385 | — |
| Mean Weekly Dose of Study Drug Over Time | Baseline up to Week 384 | Weekly dose amount was the actual total dose amounts within a week, windowed by 7-day period from Day 1. The mean weekly dose is presented for selected time periods based on timepoints reported in Outcome Measures 1 and 2. |
| Number of Participants With Dose Adjustments up to Week 52 | Baseline up to Week 52 | Dose adjustments include dose increases, dose interruptions, and dose reductions. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | Baseline up to Week 385 | An adverse event (AE) was any untoward medical event in a participant who received study drug whether or not the event is considered drug related. TEAEs were defined as any event that either began or worsened after the first administration of study drug and within 28 days of the last dose. Serious AE criteria included death, life-threatening, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed here. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. |
Countries
Puerto Rico, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Roxadustat Participants previously randomized to roxadustat received roxadustat at the same dose and frequency assigned at the last dose in the previous FibroGen study. Dose adjustments were implemented (up to a maximum roxadustat dose of 3.0 mg/kg or 400 mg, whichever is lower) every 4 weeks to maintain Hb levels at 10.0-12 g/dL. However, if a participant, at any dose, experienced an event of excessive hematopoiesis then the participant's dose was immediately reduced, or an event of rapidly declining Hb then the participant's dose was immediately increased. Participants were permitted to receive roxadustat for up to 8 years. | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 2 |
| Overall Study | Lost to Follow-up | 4 |
| Overall Study | Other | 1 |
| Overall Study | Other than Specified | 2 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Roxadustat |
|---|---|
| Age, Continuous | 64.6 years STANDARD_DEVIATION 12.02 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 13 Participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 15 |
| other Total, other adverse events | 14 / 15 |
| serious Total, serious adverse events | 9 / 15 |
Outcome results
Primary
Change From Baseline in Hb Over Time
Hb baseline was defined as the mean of the central laboratory Hb value from the baseline visit at Day 1 (prior to receiving the first dose of study drug in this study), plus any other central lab Hb values within 15 days prior to Day 1 regardless of fasting. The specific duration over which the participants were assessed was identified as over time for the endpoint in the study protocol. Therefore, to be consistent with the endpoint in the study protocol, an individual timepoint was not identified for this primary outcome measure.
Time frame: Baseline, Weeks 8, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 252, 264, 288, 312, 336, 360, and 384
Population: Participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Roxadustat | Change From Baseline in Hb Over Time | Baseline | 10.05 g/dL | Standard Deviation 0.931 |
| Roxadustat | Change From Baseline in Hb Over Time | Change at Week 8 | 1.26 g/dL | Standard Deviation 0.633 |
| Roxadustat | Change From Baseline in Hb Over Time | Change at Week 24 | 1.58 g/dL | Standard Deviation 0.959 |
| Roxadustat | Change From Baseline in Hb Over Time | Change at Week 48 | 1.94 g/dL | Standard Deviation 1.324 |
| Roxadustat | Change From Baseline in Hb Over Time | Change at Week 72 | 2.54 g/dL | Standard Deviation 1.234 |
| Roxadustat | Change From Baseline in Hb Over Time | Change at Week 96 | 1.18 g/dL | Standard Deviation 1.141 |
| Roxadustat | Change From Baseline in Hb Over Time | Change at Week 120 | 1.61 g/dL | Standard Deviation 0.815 |
| Roxadustat | Change From Baseline in Hb Over Time | Change at Week 144 | 1.96 g/dL | Standard Deviation 0.804 |
| Roxadustat | Change From Baseline in Hb Over Time | Change at Week 168 | 1.40 g/dL | Standard Deviation 1.441 |
| Roxadustat | Change From Baseline in Hb Over Time | Change at Week 192 | 1.02 g/dL | Standard Deviation 1.063 |
| Roxadustat | Change From Baseline in Hb Over Time | Change at Week 216 | 1.34 g/dL | Standard Deviation 1.062 |
| Roxadustat | Change From Baseline in Hb Over Time | Change at Week 240 | 1.02 g/dL | Standard Deviation 0.779 |
| Roxadustat | Change From Baseline in Hb Over Time | Change at Week 264 | 1.63 g/dL | Standard Deviation 1.64 |
| Roxadustat | Change From Baseline in Hb Over Time | Change at Week 288 | 0.00 g/dL | Standard Deviation 1.647 |
| Roxadustat | Change From Baseline in Hb Over Time | Change at Week 312 | 0.23 g/dL | Standard Deviation 0.416 |
| Roxadustat | Change From Baseline in Hb Over Time | Change at Week 336 | 0.70 g/dL | Standard Deviation 0 |
| Roxadustat | Change From Baseline in Hb Over Time | Change at Week 360 | -1.20 g/dL | — |
| Roxadustat | Change From Baseline in Hb Over Time | Change at Week 384 | -0.40 g/dL | — |
Secondary
Mean Weekly Dose of Study Drug Over Time
Weekly dose amount was the actual total dose amounts within a week, windowed by 7-day period from Day 1. The mean weekly dose is presented for selected time periods based on timepoints reported in Outcome Measures 1 and 2.
Time frame: Baseline up to Week 384
Population: Participants who received at least 1 dose of study drug. Here, 'Number Analyzed' signifies participants evaluable at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Roxadustat | Mean Weekly Dose of Study Drug Over Time | Week 1-4 | 257.0 mg | Standard Deviation 140.33 |
| Roxadustat | Mean Weekly Dose of Study Drug Over Time | Week 5 - 8 | 252.4 mg | Standard Deviation 115.26 |
| Roxadustat | Mean Weekly Dose of Study Drug Over Time | Week 21 - 24 | 282.3 mg | Standard Deviation 218.07 |
| Roxadustat | Mean Weekly Dose of Study Drug Over Time | Week 41 - 48 | 318.4 mg | Standard Deviation 216.9 |
| Roxadustat | Mean Weekly Dose of Study Drug Over Time | Week 61 - 72 | 236.7 mg | Standard Deviation 108.57 |
| Roxadustat | Mean Weekly Dose of Study Drug Over Time | Week 85 - 96 | 155.9 mg | Standard Deviation 114.27 |
| Roxadustat | Mean Weekly Dose of Study Drug Over Time | Week 109 - 120 | 142.8 mg | Standard Deviation 105.1 |
| Roxadustat | Mean Weekly Dose of Study Drug Over Time | Week 133 - 144 | 140.3 mg | Standard Deviation 101.03 |
| Roxadustat | Mean Weekly Dose of Study Drug Over Time | Week 157 - 168 | 152.2 mg | Standard Deviation 111.19 |
| Roxadustat | Mean Weekly Dose of Study Drug Over Time | Week 181 - 192 | 195.6 mg | Standard Deviation 184.77 |
| Roxadustat | Mean Weekly Dose of Study Drug Over Time | Week 205 - 216 | 209.4 mg | Standard Deviation 156.13 |
| Roxadustat | Mean Weekly Dose of Study Drug Over Time | Week 229 - 240 | 225.7 mg | Standard Deviation 164.58 |
| Roxadustat | Mean Weekly Dose of Study Drug Over Time | Week 253 - 264 | 327.9 mg | Standard Deviation 169.82 |
| Roxadustat | Mean Weekly Dose of Study Drug Over Time | Week 277 - 288 | 324.0 mg | Standard Deviation 190.75 |
| Roxadustat | Mean Weekly Dose of Study Drug Over Time | Week 301 - 312 | 319.2 mg | Standard Deviation 196.98 |
| Roxadustat | Mean Weekly Dose of Study Drug Over Time | Week 325 - 336 | 413.3 mg | Standard Deviation 180.37 |
| Roxadustat | Mean Weekly Dose of Study Drug Over Time | Week 349 - 360 | 389.6 mg | Standard Deviation 156.15 |
| Roxadustat | Mean Weekly Dose of Study Drug Over Time | Week 373 - 384 | 250.0 mg | — |
Secondary
Number of Participants Receiving Rescue Therapy (Composite of Blood Transfusions, Intravenous [IV] Iron, Erythropoiesis-Stimulating Agent [ESA])
Time frame: Baseline up to Week 385
Population: Participants who received at least 1 dose of study drug.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Roxadustat | Number of Participants Receiving Rescue Therapy (Composite of Blood Transfusions, Intravenous [IV] Iron, Erythropoiesis-Stimulating Agent [ESA]) | IV Iron | 5 Participants |
| Roxadustat | Number of Participants Receiving Rescue Therapy (Composite of Blood Transfusions, Intravenous [IV] Iron, Erythropoiesis-Stimulating Agent [ESA]) | ESA | 1 Participants |
| Roxadustat | Number of Participants Receiving Rescue Therapy (Composite of Blood Transfusions, Intravenous [IV] Iron, Erythropoiesis-Stimulating Agent [ESA]) | No Rescue Therapy | 8 Participants |
| Roxadustat | Number of Participants Receiving Rescue Therapy (Composite of Blood Transfusions, Intravenous [IV] Iron, Erythropoiesis-Stimulating Agent [ESA]) | Blood Transfusion | 1 Participants |
Secondary
Number of Participants With Dose Adjustments up to Week 52
Dose adjustments include dose increases, dose interruptions, and dose reductions.
Time frame: Baseline up to Week 52
Population: Participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Roxadustat | Number of Participants With Dose Adjustments up to Week 52 | Participants without Change | 1 Participants |
| Roxadustat | Number of Participants With Dose Adjustments up to Week 52 | Participants with 1 Dose Increase | 5 Participants |
| Roxadustat | Number of Participants With Dose Adjustments up to Week 52 | Participants with 2 Dose Increases | 1 Participants |
| Roxadustat | Number of Participants With Dose Adjustments up to Week 52 | Participants with >2 Dose Increases | 6 Participants |
| Roxadustat | Number of Participants With Dose Adjustments up to Week 52 | Participants with 1 Dose Interruption | 1 Participants |
| Roxadustat | Number of Participants With Dose Adjustments up to Week 52 | Participants with 2 Dose Interruptions | 1 Participants |
| Roxadustat | Number of Participants With Dose Adjustments up to Week 52 | Participants with >2 Dose Interruptions | 0 Participants |
| Roxadustat | Number of Participants With Dose Adjustments up to Week 52 | Participants with 1 Dose Reduction | 2 Participants |
| Roxadustat | Number of Participants With Dose Adjustments up to Week 52 | Participants with 2 Dose Reductions | 8 Participants |
| Roxadustat | Number of Participants With Dose Adjustments up to Week 52 | Participants with >2 Dose Reductions | 2 Participants |
Secondary
Number of Participants With Hb ≥10 g/dL
Hb baseline was defined as the mean of the central laboratory Hb value from the baseline visit at Day 1 (prior to receiving the first dose of study drug in this study), plus any other central lab Hb values within 15 days prior to Day 1 regardless of fasting.
Time frame: Baseline up to Week 384
Population: Participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Roxadustat | Number of Participants With Hb ≥10 g/dL | Baseline | 9 Participants |
| Roxadustat | Number of Participants With Hb ≥10 g/dL | Week 8 | 13 Participants |
| Roxadustat | Number of Participants With Hb ≥10 g/dL | Week 24 | 13 Participants |
| Roxadustat | Number of Participants With Hb ≥10 g/dL | Week 48 | 13 Participants |
| Roxadustat | Number of Participants With Hb ≥10 g/dL | Week 72 | 11 Participants |
| Roxadustat | Number of Participants With Hb ≥10 g/dL | Week 96 | 7 Participants |
| Roxadustat | Number of Participants With Hb ≥10 g/dL | Week 120 | 8 Participants |
| Roxadustat | Number of Participants With Hb ≥10 g/dL | Week 144 | 7 Participants |
| Roxadustat | Number of Participants With Hb ≥10 g/dL | Week 168 | 5 Participants |
| Roxadustat | Number of Participants With Hb ≥10 g/dL | Week 192 | 5 Participants |
| Roxadustat | Number of Participants With Hb ≥10 g/dL | Week 216 | 5 Participants |
| Roxadustat | Number of Participants With Hb ≥10 g/dL | Week 240 | 5 Participants |
| Roxadustat | Number of Participants With Hb ≥10 g/dL | Week 264 | 4 Participants |
| Roxadustat | Number of Participants With Hb ≥10 g/dL | Week 288 | 3 Participants |
| Roxadustat | Number of Participants With Hb ≥10 g/dL | Week 312 | 3 Participants |
| Roxadustat | Number of Participants With Hb ≥10 g/dL | Week 336 | 2 Participants |
| Roxadustat | Number of Participants With Hb ≥10 g/dL | Week 360 | 1 Participants |
| Roxadustat | Number of Participants With Hb ≥10 g/dL | Week 384 | 1 Participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
An adverse event (AE) was any untoward medical event in a participant who received study drug whether or not the event is considered drug related. TEAEs were defined as any event that either began or worsened after the first administration of study drug and within 28 days of the last dose. Serious AE criteria included death, life-threatening, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed here. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Time frame: Baseline up to Week 385
Population: Participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Roxadustat | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | Any TEAEs | 14 Participants |
| Roxadustat | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | Serious TEAEs | 9 Participants |