Anemia, Dialysis-Dependent Chronic Kidney Disease
Conditions
Keywords
anemia, kidney, dialysis-dependent chronic kidney disease, CKD, DD-CKD, renal, vadadustat, AKB-6548, hypoxia-inducible factor, HIF, hypoxia-inducible factor prolyl-hydroxylase inhibitor, HIF-PHI, hyporesponder, hyporesponsive, epoetin alfa, hemoglobin, erythropoiesis stimulating agent, ESA
Brief summary
This is a Phase 2, randomized, open-label study to evaluate vadadustat versus epoetin alfa for the treatment of anemia in subjects with Dialysis-dependent Chronic Kidney Disease (DD-CKD) who are hyporesponsive to erythropoiesis stimulating agents (ESAs.)
Interventions
DRUGvadadustat
vadadustat
DRUGepoetin alfa
epoetin alfa
Sponsors
Akebia Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male and female subjects ≥18 years of age * Receiving chronic maintenance hemodialysis for end-stage kidney disease * Currently receiving epoetin alfa for anemia * Hb between 8.5 and 10.0 g/dL during screening
Exclusion criteria
* Anemia due to a cause other than CKD or presence of active bleeding or recent blood loss * Sickle cell disease, myelodysplastic syndromes, bone marrow fibrosis, hematologic malignancy, myeloma, hemolytic anemia, thalassemia, or pure red cell aplasia * Red blood cell transfusion within 4 weeks prior to or during screening * Anticipated to recover adequate kidney function to no longer require hemodialysis during study participation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change From Baseline in Hemoglobin (Hb) Over Time During the Treatment Period | Baseline; up to 20 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Hb Values Within the Target Range of 10.0-11.0 Grams Per Deciliter (g/dL) During the Treatment Period | Baseline; up to 20 weeks | — |
| Number of Participants Receiving Epoetin Alfa Rescue | up to 20 weeks | — |
| Number of Participants Receiving Red Blood Cell Transfusion | up to 20 weeks | — |
| Number of Participants With Specified Levels of Various Biomarkers, Including C-reactive Protein, Hepcidin, and Vascular Endothelial Growth Factor | up to 20 weeks | — |
| Number of Participants Demonstrating Incremental Increases in Hb From Baseline Over Time During the Treatment Period | Baseline; up to 20 weeks | — |
| Number of Participants Maintaining Iron Sufficiency (Defined as Ferritin ≥100 Nanograms Per Milliliter and Transferrin Saturation ≥20%) | up to 20 weeks | — |
| Number of Participants Utilizing Resources | up to 20 weeks | — |
| Number of Participants With Treatment-emergent Adverse Events | up to 24 weeks | Treatment-emergent adverse events were collected in all participants enrolled in the study. |
| Mean Weekly Dose of Intravenous Elemental Iron Administered | up to 20 weeks | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Vadadustat Participants were to discontinue epoetin alfa, administered during the 28-day Screening Period, and initiate vadadustat on Day 1 of the 20-week treatment period. The vadadustat daily oral dose was adjustable based on the target hemoglobin (Hb) level of 10.0 to 11.0 grams per deciliter (g/dL). | 0 |
| Epoetin Alfa Participants were to receive the same dose of epoetin alfa administered during the 28-day Screening Period starting on Day 1 of the 20-week Treatment Period. Epoetin alfa was administered based on the approved label for adult participants with Chronic Kidney Disease (CKD) on dialysis, and the dose was adjustable based on Hb level, as clinically indicated throughout the study. | 2 |
| Total | 2 |
Baseline characteristics
| Characteristic | Epoetin Alfa | Total |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | NA Participants | NA Participants |
| Race (NIH/OMB) Asian | NA Participants | NA Participants |
| Race (NIH/OMB) Black or African American | NA Participants | NA Participants |
| Race (NIH/OMB) More than one race | NA Participants | NA Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | NA Participants | NA Participants |
| Race (NIH/OMB) Unknown or Not Reported | NA Participants | NA Participants |
| Race (NIH/OMB) White | NA Participants | NA Participants |
| Sex: Female, Male Female | NA Participants | NA Participants |
| Sex: Female, Male Male | NA Participants | NA Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 2 |
| other Total, other adverse events | 0 / 0 | 0 / 2 |
| serious Total, serious adverse events | 0 / 0 | 0 / 2 |
Outcome results
Primary
Change From Baseline in Hemoglobin (Hb) Over Time During the Treatment Period
Time frame: Baseline; up to 20 weeks
Population: No efficacy analyses were conducted due to the limited number of participants enrolled prior to study termination (N=2). In order to protect the privacy of participants, the results of enrolled participants cannot be reported.
Secondary
Mean Weekly Dose of Intravenous Elemental Iron Administered
Time frame: up to 20 weeks
Population: No efficacy analyses were conducted due to the limited number of participants enrolled prior to study termination (N=2). In order to protect the privacy of participants, the results of enrolled participants cannot be reported.
Secondary
Number of Participants Demonstrating Incremental Increases in Hb From Baseline Over Time During the Treatment Period
Time frame: Baseline; up to 20 weeks
Population: No efficacy analyses were conducted due to the limited number of participants enrolled prior to study termination (N=2). In order to protect the privacy of participants, the results of enrolled participants cannot be reported.
Secondary
Number of Participants Maintaining Iron Sufficiency (Defined as Ferritin ≥100 Nanograms Per Milliliter and Transferrin Saturation ≥20%)
Time frame: up to 20 weeks
Population: No efficacy analyses were conducted due to the limited number of participants enrolled prior to study termination (N=2). In order to protect the privacy of participants, the results of enrolled participants cannot be reported.
Secondary
Number of Participants Receiving Epoetin Alfa Rescue
Time frame: up to 20 weeks
Population: No efficacy analyses were conducted due to the limited number of participants enrolled prior to study termination (N=2). In order to protect the privacy of participants, the results of enrolled participants cannot be reported.
Secondary
Number of Participants Receiving Red Blood Cell Transfusion
Time frame: up to 20 weeks
Population: No efficacy analyses were conducted due to the limited number of participants enrolled prior to study termination (N=2). In order to protect the privacy of participants, the results of enrolled participants cannot be reported.
Secondary
Number of Participants Utilizing Resources
Time frame: up to 20 weeks
Population: No efficacy analyses were conducted due to the limited number of participants enrolled prior to study termination (N=2). In order to protect the privacy of participants, the results of enrolled participants cannot be reported.
Secondary
Number of Participants With Hb Values Within the Target Range of 10.0-11.0 Grams Per Deciliter (g/dL) During the Treatment Period
Time frame: Baseline; up to 20 weeks
Population: No efficacy analyses were conducted due to the limited number of participants enrolled prior to study termination (N=2). In order to protect the privacy of participants, the results of enrolled participants cannot be reported.
Secondary
Number of Participants With Specified Levels of Various Biomarkers, Including C-reactive Protein, Hepcidin, and Vascular Endothelial Growth Factor
Time frame: up to 20 weeks
Population: No efficacy analyses were conducted due to the limited number of participants enrolled prior to study termination (N=2). In order to protect the privacy of participants, the results of enrolled participants cannot be reported.
Secondary
Number of Participants With Treatment-emergent Adverse Events
Treatment-emergent adverse events were collected in all participants enrolled in the study.
Time frame: up to 24 weeks
Population: All participants enrolled in the study
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vadadustat | Number of Participants With Treatment-emergent Adverse Events | 0 Participants |
| Epoetin Alfa | Number of Participants With Treatment-emergent Adverse Events | 0 Participants |