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CompletedNCT02648347Updated Jun 27, 2022Results posted

Study to Evaluate Vadadustat for the Correction of Anemia in Participants With Non-dialysis-dependent Chronic Kidney Disease

A Phase 3 interventional study of Vadadustat and Darbepoetin alfa in Anemia and Non-Dialysis-Dependent Chronic Kidney Disease, sponsored by Akebia Therapeutics. Completed at 439 sites in 20 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-06-27.

Sponsored by Akebia Therapeutics · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
1,751
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

A multicenter, randomized, open-label, active-controlled Phase 3 study for the correction of anemia and maintenance of hemoglobin (Hb) in participants with Non-Dialysis-Dependent Chronic Kidney Disease (NDD-CKD)

Read the detailed description

This is a multicenter, randomized, open-label, active-controlled Phase 3 study of the efficacy and safety of vadadustat versus Darbepoetin alfa for the correction of anemia and maintenance of Hb in participants with NDD-CKD

02

Conditions studied

  • Anemia
  • Non-Dialysis-Dependent Chronic Kidney Disease

Keywords

  • Vadadustat
  • AKB-6548
  • Chronic kidney disease
  • anemia
  • CKD
  • chronic renal insufficiency
  • renal impairment
  • erythropoietin
  • kidney
  • renal
  • oral anemia treatment
  • hemoglobin
  • hypoxia-inducible factor
  • HIF
  • hypoxia-inducible factor prolyl-hydroxylase inhibitor
  • HIF-PHI
  • efficacy
  • safety
  • Phase 3
  • cardiovascular
  • NDD-CKD
03

In context

Anemia

1,768 studies on the registry are indexed under Anemia; 244 are open to participants now.

This study's enrollment of 1,751 is above the median of 96 across 1,318 interventional studies indexed under Anemia.

Browse Anemia studies →

Lead sponsor

Akebia Therapeutics is the lead sponsor of 37 studies on the registry; 3 are open to participants now.

Of its 22 completed or terminated interventional studies of FDA-regulated products, 12 (55%) have results posted.

Browse Akebia Therapeutics studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • ≥18 years of age
  • Diagnosis of chronic kidney disease (CKD) with an estimated glomerular filtration rate ≤60 milliliters per minute per 1.73 square meter (mL/min/1.73 m\^2) at Screening and not expected to start dialysis within 6 months of Screening
  • Mean Screening hemoglobin \<10.0 grams per deciliter (g/dL)
  • Serum ferritin ≥100 nanograms per milliliter (ng/mL) and transferrin saturation (TSAT) ≥20% during Screening

Exclusion criteria

Exclusion Criteria:

  • Anemia due to a cause other than CKD or participants with active bleeding or recent blood loss
  • Red blood cell transfusion within 8 weeks prior to randomization.
  • Any erythropoietic stimulating agent within 8 weeks prior to randomization
  • Uncontrolled hypertension
  • Severe heart failure at Screening (New York Heart Association Class IV)
  • Acute coronary syndrome (hospitalization for unstable angina or myocardial infarction), surgical or percutaneous intervention for coronary, cerebrovascular, or peripheral artery disease (aortic or lower extremity), surgical or percutaneous valvular replacement or repair, sustained ventricular tachycardia, hospitalization for heart failure, or stroke within 12 weeks prior to or during Screening
  • Hypersensitivity to Darbepoetin or Vadadustat or to any of their excipients
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
1,751 participants (actual)

Study arms

  • Experimental
    Vadadustat

    Drug: Vadadustat

  • Active comparator
    Darbepoetin alfa

    Drug: Darbepoetin alfa

Interventions

  • DrugVadadustat

    Oral dose administered once daily for ≥36 weeks. Dose adjustment based on hemoglobin level as defined in the protocol.

    Also known as: AKB-6548

  • DrugDarbepoetin alfa

    Subcutaneous or intravenous dose administered for ≥36 weeks. Initial dose based on the current package insert for investigational sites in the United States (US), and the Summary of Product Characteristics for all other investigational sites (non-US) for adult participants with chronic kidney disease not on dialysis.

    Also known as: Aranesp

06

What researchers measure

Primary outcomes

  1. Change From Baseline in Hemoglobin (Hb) to the Average Over the Primary Efficacy Period (Weeks 24 to 36)

    The Baseline average was calculated as the average of the Hb values obtained at the screening visit closest to the date of randomization and the randomization visit. The average for the Primary Efficacy Period was calculated as the average Hb value over Weeks 24 to 36. Analysis was conducted using an analysis of covariance (ANCOVA) model with multiple imputation for missing data with Baseline Hb concentration (\<9.5 versus ≥9.5 grams per deciliter \[g/dL\]), geographic region (United States \[US\] versus European Union \[EU\] versus Rest of World \[ROW\]), and New York Heart Association congestive heart failure (NYHA CHF) class (Class 0 \[no CHF\] or I versus II or III) as covariates.

    Time frame: Baseline; Weeks 24 to 36

  2. Median Time to First Major Adverse Cardiovascular Event (MACE)

    MACE was defined as all-cause mortality, non-fatal myocardial infarction (MI), or non-fatal stroke. The primary safety outcome was positively adjudicated first MACE, which was defined as any death, Endpoint Adjudication Committee (EAC)-confirmed non-fatal MI, or EAC-confirmed non-fatal stroke occurring between the first dose date and each participant's last participation date. PROTECT MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0014 (NCT02648347) and AKB-6548-CI-0015 (NCT02680574). Results and statistical analysis from study AKB-6548-CI-0014 has been reported in below table and under section "Statistical Analysis 1". Results and statistical analysis of the pooled data from studies AKB-6548-CI-0014 and AKB-6548-CI-0015 has been reported under section "Statistical Analysis 2" of this outcome measure.

    Time frame: Up to Week 208

Secondary outcomes

  1. Change From Baseline in Hb to the Average Over the Secondary Efficacy Period (Weeks 40 to 52)

    The Baseline average was calculated as the average of the Hb values obtained at the screening visit closest to the date of randomization and the randomization visit. The average for the Secondary Efficacy Period was calculated as the average Hb value over Weeks 40 to 52. Analysis was conducted using an ANCOVA model with multiple imputation for missing data with Baseline Hb concentration (\<9.5 versus ≥9.5 g/dL), geographic region (US versus EU versus ROW), and NYHA CHF class (Class 0 \[no CHF\] or I versus II or III) as covariates.

    Time frame: Baseline; Weeks 40 to 52

  2. Median Time to First MACE Plus Hospitalization for Heart Failure or Thromboembolic Event Excluding Vascular Access Thrombosis

    MACE was defined as all-cause mortality, non-fatal MI, or non-fatal stroke. Hospitalization for EAC adjudicated heart failure included presentation of participants to an acute care facility requiring an overnight hospitalization (change in calendar day) with an exacerbation of heart failure requiring treatment. EAC confirmed thromboembolic events for this secondary outcome measure included arterial thrombosis, deep vein thrombosis, and pulmonary embolism. PROTECT MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0014 (NCT02648347) and AKB-6548-CI-0015 (NCT02680574). Results and statistical analysis from study AKB-6548-CI-0014 has been reported in below table and under section "Statistical Analysis 1". Results and statistical analysis of the pooled data from studies AKB-6548-CI-0014 and AKB-6548-CI-0015 has been reported under section "Statistical Analysis 2" of this outcome measure.

    Time frame: Up to Week 208

  3. Median Time to First Cardiovascular MACE

    MACE was defined as all-cause mortality, non-fatal MI, or non-fatal stroke. Cardiovascular MACE analysis differed from the primary MACE endpoint as it included only deaths adjudicated by the EAC as cardiovascular deaths (i.e, only EAC-confirmed cardiovascular deaths) in addition to first events of non-fatal MI or non-fatal stroke. PROTECT MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0014 (NCT02648347) and AKB-6548-CI-0015 (NCT02680574). Results and statistical analysis from study AKB-6548-CI-0014 has been reported in below table and under section "Statistical Analysis 1". Results and statistical analysis of the pooled data from studies AKB-6548-CI-0014 and AKB-6548-CI-0015 has been reported under section "Statistical Analysis 2" of this outcome measure.

    Time frame: Up to Week 208

  4. Median Time to First Cardiovascular Death

    Cardiovascular death included EAC adjudicated fatal MI, pump failure, sudden death, presumed sudden death, fatal stroke, fatal pulmonary embolism, cardiovascular procedure-related death, other cardiovascular death, and presumed cardiovascular death. PROTECT MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0014 (NCT02648347) and AKB-6548-CI-0015 (NCT02680574). Results and statistical analysis from study AKB-6548-CI-0014 has been reported in below table and under section "Statistical Analysis 1". Results and statistical analysis of the pooled data from studies AKB-6548-CI-0014 and AKB-6548-CI-0015 has been reported under section "Statistical Analysis 2" of this outcome measure.

    Time frame: Up to Week 208

  5. Median Time to First All-cause Mortality

    Only events that were positively adjudicated and confirmed by the EAC were included in the MACE analyses. PROTECT MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0014 (NCT02648347) and AKB-6548-CI-0015 (NCT02680574). Results and statistical analysis from study AKB-6548-CI-0014 has been reported in below table and under section "Statistical Analysis 1". Results and statistical analysis of the pooled data from studies AKB-6548-CI-0014 and AKB-6548-CI-0015 has been reported under section "Statistical Analysis 2" of this outcome measure.

    Time frame: Up to Week 208

Other outcomes

  1. Exploratory - Proportion of Participants With Hb Values Within the Target Range During the Primary Evaluation Period (Weeks 24 to 36)

    Time frame: Weeks 24 to 36

  2. Exploratory - Proportion of Time With Hb Values Within the Target Range During the Primary Evaluation Period (Weeks 24 to 36)

    Time frame: Weeks 24 to 36

  3. Exploratory - Proportion of Time With Hb Values Within the Target Range During the Secondary Evaluation Period (Weeks 40 to 52)

    Time frame: Weeks 40 to 52

  4. Exploratory - Proportion of Participants With Hb Values Within the Target Range During the Secondary Evaluation Period (Weeks 40 to 52)

    Time frame: Weeks 40 to 52

  5. Exploratory - Proportion of Participants With an Hb Increase of >1.0 g/dL From Baseline Visit

    Time frame: Baseline; up to Week 52

  6. Exploratory - Time to Achieve Hb Increase of >1.0 g/dL From Baseline Visit

    Time frame: Baseline; up to Week 52

  7. Exploratory - Mean Change in Hb Between Baseline (Mean Pretreatment Hb) and the Primary Evaluation Period (Mean Hb From Weeks 24 to 36) Stratified by Pre-baseline Erythropoiesis-stimulating Agent (ESA) Exposure

    Time frame: Baseline; Weeks 24 to 36

  8. Exploratory - Mean Monthly Dose of Intravenous (IV) Elemental Iron Administered in Participants Who Have Received IV Iron

    Time frame: Up to Week 52

  9. Exploratory - Proportion of Participants Receiving IV Iron Therapy

    Time frame: Up to Week 52

  10. Exploratory - Proportion of Participants Receiving Red Blood Cells (RBCs) Transfusion(s)

    Time frame: Up to Week 52

07

Results

Posted Jun 27, 2022

Participant flow

Participant flow — Overall Study
MilestoneVadadustatDarbepoetin Alfa
Started879872
Completed670675
Not completed209197
Withdrew: Death174167
Withdrew: Withdrawal by subject169
Withdrew: Lost to follow-up1821
Withdrew: Missing10

Outcome measures

PrimaryChange From Baseline in Hemoglobin (Hb) to the Average Over the Primary Efficacy Period (Weeks 24 to 36)

The Baseline average was calculated as the average of the Hb values obtained at the screening visit closest to the date of randomization and the randomization visit. The average for the Primary Efficacy Period was calculated as the average Hb value over Weeks 24 to 36. Analysis was conducted using an analysis of covariance (ANCOVA) model with multiple imputation for missing data with Baseline Hb concentration (\<9.5 versus ≥9.5 grams per deciliter \[g/dL\]), geographic region (United States \[US\] versus European Union \[EU\] versus Rest of World \[ROW\]), and New York Heart Association congestive heart failure (NYHA CHF) class (Class 0 \[no CHF\] or I versus II or III) as covariates.

Time frame:
Baseline; Weeks 24 to 36
Reported as:
Least squares mean · g/dL
Change From Baseline in Hemoglobin (Hb) to the Average Over the Primary Efficacy Period (Weeks 24 to 36)
g/dLVadadustatDarbepoetin Alfa
Change From Baseline in Hemoglobin (Hb) to the Average Over the Primary Efficacy Period (Weeks 24 to 36)1.43 ± 0.0461.38 ± 0.047
Statistical analysis
  • Vadadustat vs Darbepoetin Alfa · Least squares mean difference: 0.05 · 95% CI -0.04 to 0.15
PrimaryMedian Time to First Major Adverse Cardiovascular Event (MACE)

MACE was defined as all-cause mortality, non-fatal myocardial infarction (MI), or non-fatal stroke. The primary safety outcome was positively adjudicated first MACE, which was defined as any death, Endpoint Adjudication Committee (EAC)-confirmed non-fatal MI, or EAC-confirmed non-fatal stroke occurring between the first dose date and each participant's last participation date. PROTECT MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0014 (NCT02648347) and AKB-6548-CI-0015 (NCT02680574). Results and statistical analysis from study AKB-6548-CI-0014 has been reported in below table and under section "Statistical Analysis 1". Results and statistical analysis of the pooled data from studies AKB-6548-CI-0014 and AKB-6548-CI-0015 has been reported under section "Statistical Analysis 2" of this outcome measure.

Time frame:
Up to Week 208
Reported as:
Median · Weeks
Median Time to First Major Adverse Cardiovascular Event (MACE)
WeeksVadadustatDarbepoetin Alfa
Median Time to First Major Adverse Cardiovascular Event (MACE)45.71 (21.71 to 83.14)46.71 (25.93 to 85.57)
Statistical analysis
  • Vadadustat vs Darbepoetin Alfa · Log Rank · p = =0.2050 · Hazard ratio (hr): 1.16 · 95% CI 0.955 to 1.412
  • Vadadustat vs Darbepoetin Alfa · Log Rank · p = =0.0725 · Hazard ratio (hr): 1.17 · 95% CI 1.012 to 1.355Based on non-parametric analysis.
SecondaryChange From Baseline in Hb to the Average Over the Secondary Efficacy Period (Weeks 40 to 52)

The Baseline average was calculated as the average of the Hb values obtained at the screening visit closest to the date of randomization and the randomization visit. The average for the Secondary Efficacy Period was calculated as the average Hb value over Weeks 40 to 52. Analysis was conducted using an ANCOVA model with multiple imputation for missing data with Baseline Hb concentration (\<9.5 versus ≥9.5 g/dL), geographic region (US versus EU versus ROW), and NYHA CHF class (Class 0 \[no CHF\] or I versus II or III) as covariates.

Time frame:
Baseline; Weeks 40 to 52
Reported as:
Least squares mean · g/dL
Change From Baseline in Hb to the Average Over the Secondary Efficacy Period (Weeks 40 to 52)
g/dLVadadustatDarbepoetin Alfa
Change From Baseline in Hb to the Average Over the Secondary Efficacy Period (Weeks 40 to 52)1.52 ± 0.0521.48 ± 0.053
Statistical analysis
  • Vadadustat vs Darbepoetin Alfa · Least squares mean difference: 0.04 · 95% CI -0.06 to 0.14
SecondaryMedian Time to First MACE Plus Hospitalization for Heart Failure or Thromboembolic Event Excluding Vascular Access Thrombosis

MACE was defined as all-cause mortality, non-fatal MI, or non-fatal stroke. Hospitalization for EAC adjudicated heart failure included presentation of participants to an acute care facility requiring an overnight hospitalization (change in calendar day) with an exacerbation of heart failure requiring treatment. EAC confirmed thromboembolic events for this secondary outcome measure included arterial thrombosis, deep vein thrombosis, and pulmonary embolism. PROTECT MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0014 (NCT02648347) and AKB-6548-CI-0015 (NCT02680574). Results and statistical analysis from study AKB-6548-CI-0014 has been reported in below table and under section "Statistical Analysis 1". Results and statistical analysis of the pooled data from studies AKB-6548-CI-0014 and AKB-6548-CI-0015 has been reported under section "Statistical Analysis 2" of this outcome measure.

Time frame:
Up to Week 208
Reported as:
Median · Weeks
Median Time to First MACE Plus Hospitalization for Heart Failure or Thromboembolic Event Excluding Vascular Access Thrombosis
WeeksVadadustatDarbepoetin Alfa
Median Time to First MACE Plus Hospitalization for Heart Failure or Thromboembolic Event Excluding Vascular Access Thrombosis37.64 (17.14 to 74.14)41.43 (21.71 to 75.14)
Statistical analysis
  • Vadadustat vs Darbepoetin Alfa · Log Rank · p = =0.1743 · Hazard ratio (hr): 1.16 · 95% CI 0.966 to 1.382Based on non-parametric analysis.
  • Vadadustat vs Darbepoetin Alfa · Log Rank · p = =0.2305 · Hazard ratio (hr): 1.11 · 95% CI 0.972 to 1.267Based on non-parametric analysis.
SecondaryMedian Time to First Cardiovascular MACE

MACE was defined as all-cause mortality, non-fatal MI, or non-fatal stroke. Cardiovascular MACE analysis differed from the primary MACE endpoint as it included only deaths adjudicated by the EAC as cardiovascular deaths (i.e, only EAC-confirmed cardiovascular deaths) in addition to first events of non-fatal MI or non-fatal stroke. PROTECT MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0014 (NCT02648347) and AKB-6548-CI-0015 (NCT02680574). Results and statistical analysis from study AKB-6548-CI-0014 has been reported in below table and under section "Statistical Analysis 1". Results and statistical analysis of the pooled data from studies AKB-6548-CI-0014 and AKB-6548-CI-0015 has been reported under section "Statistical Analysis 2" of this outcome measure.

Time frame:
Up to Week 208
Reported as:
Median · Weeks
Median Time to First Cardiovascular MACE
WeeksVadadustatDarbepoetin Alfa
Median Time to First Cardiovascular MACE45.86 (22.29 to 78.86)41.86 (20.29 to 90.00)
Statistical analysis
  • Vadadustat vs Darbepoetin Alfa · Gray's Test · p = =0.3154 · Hazard ratio (hr): 1.19 · 95% CI 0.901 to 1.564Based on non-parametric analysis.
  • Vadadustat vs Darbepoetin Alfa · Gray's Test · p = =0.2531 · Hazard ratio (hr): 1.16 · 95% CI 0.947 to 1.420Based on non-parametric analysis.
SecondaryMedian Time to First Cardiovascular Death

Cardiovascular death included EAC adjudicated fatal MI, pump failure, sudden death, presumed sudden death, fatal stroke, fatal pulmonary embolism, cardiovascular procedure-related death, other cardiovascular death, and presumed cardiovascular death. PROTECT MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0014 (NCT02648347) and AKB-6548-CI-0015 (NCT02680574). Results and statistical analysis from study AKB-6548-CI-0014 has been reported in below table and under section "Statistical Analysis 1". Results and statistical analysis of the pooled data from studies AKB-6548-CI-0014 and AKB-6548-CI-0015 has been reported under section "Statistical Analysis 2" of this outcome measure.

Time frame:
Up to Week 208
Reported as:
Median · Weeks
Median Time to First Cardiovascular Death
WeeksVadadustatDarbepoetin Alfa
Median Time to First Cardiovascular Death48.29 (28.86 to 83.14)41.86 (16.00 to 92.29)
Statistical analysis
  • Vadadustat vs Darbepoetin Alfa · Gray's test · p = =0.5991 · Hazard ratio (hr): 1.13 · 95% CI 0.808 to 1.594Based on non-parametric analysis.
  • Vadadustat vs Darbepoetin Alfa · Gray's test · p = =0.8613 · Hazard ratio (hr): 1.01 · 95% CI 0.792 to 1.293Based on non-parametric analysis.
SecondaryMedian Time to First All-cause Mortality

Only events that were positively adjudicated and confirmed by the EAC were included in the MACE analyses. PROTECT MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0014 (NCT02648347) and AKB-6548-CI-0015 (NCT02680574). Results and statistical analysis from study AKB-6548-CI-0014 has been reported in below table and under section "Statistical Analysis 1". Results and statistical analysis of the pooled data from studies AKB-6548-CI-0014 and AKB-6548-CI-0015 has been reported under section "Statistical Analysis 2" of this outcome measure.

Time frame:
Up to Week 208
Reported as:
Median · Weeks
Median Time to First All-cause Mortality
WeeksVadadustatDarbepoetin Alfa
Median Time to First All-cause Mortality46.57 (22.29 to 84.36)47.79 (27.36 to 88.79)
Statistical analysis
  • Vadadustat vs Darbepoetin Alfa · Log Rank · p = =0.4388 · Hazard ratio (hr): 1.11 · 95% CI 0.902 to 1.375Based on non-parametric analysis.
  • Vadadustat vs Darbepoetin Alfa · Log Rank · p = =0.4577 · Hazard ratio (hr): 1.09 · 95% CI 0.930 to 1.274Based on non-parametric analysis.
Other pre-specifiedExploratory - Proportion of Participants With Hb Values Within the Target Range During the Primary Evaluation Period (Weeks 24 to 36)
Time frame:
Weeks 24 to 36

Results for this outcome have not been posted.

Other pre-specifiedExploratory - Proportion of Time With Hb Values Within the Target Range During the Primary Evaluation Period (Weeks 24 to 36)
Time frame:
Weeks 24 to 36

Results for this outcome have not been posted.

Other pre-specifiedExploratory - Proportion of Time With Hb Values Within the Target Range During the Secondary Evaluation Period (Weeks 40 to 52)
Time frame:
Weeks 40 to 52

Results for this outcome have not been posted.

Other pre-specifiedExploratory - Proportion of Participants With Hb Values Within the Target Range During the Secondary Evaluation Period (Weeks 40 to 52)
Time frame:
Weeks 40 to 52

Results for this outcome have not been posted.

Other pre-specifiedExploratory - Proportion of Participants With an Hb Increase of >1.0 g/dL From Baseline Visit
Time frame:
Baseline; up to Week 52

Results for this outcome have not been posted.

Other pre-specifiedExploratory - Time to Achieve Hb Increase of >1.0 g/dL From Baseline Visit
Time frame:
Baseline; up to Week 52

Results for this outcome have not been posted.

Other pre-specifiedExploratory - Mean Change in Hb Between Baseline (Mean Pretreatment Hb) and the Primary Evaluation Period (Mean Hb From Weeks 24 to 36) Stratified by Pre-baseline Erythropoiesis-stimulating Agent (ESA) Exposure
Time frame:
Baseline; Weeks 24 to 36

Results for this outcome have not been posted.

Other pre-specifiedExploratory - Mean Monthly Dose of Intravenous (IV) Elemental Iron Administered in Participants Who Have Received IV Iron
Time frame:
Up to Week 52

Results for this outcome have not been posted.

Other pre-specifiedExploratory - Proportion of Participants Receiving IV Iron Therapy
Time frame:
Up to Week 52

Results for this outcome have not been posted.

Other pre-specifiedExploratory - Proportion of Participants Receiving Red Blood Cells (RBCs) Transfusion(s)
Time frame:
Up to Week 52

Results for this outcome have not been posted.

Adverse events

Collected over Up to 208 weeks. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Vadadustat180/878 (20.5%)573/878 (65.3%)561/878 (63.9%)
Darbepoetin Alfa168/870 (19.3%)561/870 (64.5%)565/870 (64.9%)
Most frequent serious events
Showing 10 of 653
Most frequent serious events
EventVadadustatDarbepoetin Alfa
End stage renal diseaseRenal and urinary disorders292/878292/870
PneumoniaInfections and infestations60/87849/870
Acute kidney injuryRenal and urinary disorders42/87840/870
Cardiac failure congestiveCardiac disorders40/87839/870
Fluid overloadMetabolism and nutrition disorders34/87822/870
Acute myocardial infarctionCardiac disorders32/87827/870
SepsisInfections and infestations28/87819/870
HyperkalaemiaMetabolism and nutrition disorders20/87826/870
Cardiac failure acuteCardiac disorders21/87824/870
AnaemiaBlood and lymphatic system disorders18/87824/870
Most frequent other events
Showing 10 of 22
Most frequent other events
EventVadadustatDarbepoetin Alfa
HypertensionVascular disorders151/878186/870
HyperkalaemiaMetabolism and nutrition disorders93/878121/870
DiarrhoeaGastrointestinal disorders114/87885/870
Oedema peripheralGeneral disorders110/87889/870
Urinary tract infectionInfections and infestations98/87894/870
NauseaGastrointestinal disorders87/87871/870
FallInjury, poisoning and procedural complications74/87880/870
ConstipationGastrointestinal disorders74/87872/870
Upper respiratory tract infectionInfections and infestations50/87870/870
HyperphosphataemiaMetabolism and nutrition disorders64/87863/870

Baseline characteristics

Age, Continuous
Age, Continuous(Years)VadadustatDarbepoetin AlfaTotal
Mean65.2 ± 14.2764.9 ± 13.7165.0 ± 13.99
Sex: Female, Male
Sex: Female, Male(Participants)VadadustatDarbepoetin AlfaTotal
Female475506981
Male404366770
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)VadadustatDarbepoetin AlfaTotal
American Indian or Alaska Native222345
Asian483785
Black or African American188172360
Native Hawaiian or Other Pacific Islander6612
White5465711117
Not Reported5611
Reported as Other5848106
Multiple6915
Mean hemoglobin
Mean hemoglobin(Grams per deciliter (g/dL))VadadustatDarbepoetin AlfaTotal
Mean9.113 ± 0.80159.142 ± 0.77909.128 ± 0.7903
Mean estimated glomerular filtration rate
Mean estimated glomerular filtration rate(mL/min/1.73m^2)VadadustatDarbepoetin AlfaTotal
Mean21.2 ± 11.9921.9 ± 12.6021.5 ± 12.30
Number of Participants with History of Diabetes
Number of Participants with History of Diabetes(Participants)VadadustatDarbepoetin AlfaTotal
Count of participants5075141021
Number of Participants with NYHA Functional Classification of Heart Failure
Number of Participants with NYHA Functional Classification of Heart Failure(Participants)VadadustatDarbepoetin AlfaTotal
NYHA Class 06136011214
NYHA Class I136123259
NYHA Class II100119219
NYHA Class III242549
NYHA Class IV213
NYHA Class Missing437
Number of Participants with Any History of Heart Failure
Number of Participants with Any History of Heart Failure(Participants)VadadustatDarbepoetin AlfaTotal
Yes363874
No6246091233
Missing219225444
08

Study locations

439 sites
  • Research Site
    Huntsville, Alabama 35805, United States
  • Research Site
    Tuscumbia, Alabama 35674, United States
  • Research Site
    Glendale, Arizona 85306, United States
  • Research Site
    Mesa, Arizona 85210, United States
  • Research Site
    Phoenix, Arizona 85027, United States
  • Research Site
    Tucson, Arizona 85718, United States
  • Research Site
    Tucson, Arizona 85724, United States
  • Research Site
    Anaheim, California 92801, United States
  • Research Site
    Bakersfield, California 93309, United States
  • Research Site #1
    Chula Vista, California 91910, United States
  • Research Site #2
    Chula Vista, California 91910, United States
  • Research Site #1
    Fountain Valley, California 92708, United States
  • Research Site #2
    Fountain Valley, California 92708, United States
  • Research Site
    Glendale, California 91206, United States
  • Research Site
    Granada Hills, California 91344, United States
  • Research Site
    La Mesa, California 91942, United States
  • Research Site
    Laguna Hills, California 92653, United States
  • Research Site
    Long Beach, California 90807, United States
  • Research Site
    Long Beach, California 92886, United States
  • Research Site
    Los Angeles, California 90020, United States
  • Research Site
    Lynwood, California 90262, United States
  • Research Site #2
    Northridge, California 91324, United States
  • Research Site
    Northridge, California 91324, United States
  • Research Site
    Riverside, California 92505, United States
  • Research Site
    Roseville, California 95661, United States
  • Research Site
    Sacramento, California 95825, United States
  • Research Site
    Salinas, California 93901, United States
  • Research Site
    San Diego, California 92103-6204, United States
  • Research Site #1
    San Dimas, California 91773, United States
  • Research Site #2
    San Dimas, California 91773, United States
  • Research Site
    Santa Ana, California 92704, United States
  • Research Site
    Santa Monica, California 90404, United States
  • Research Site
    Sherman Oaks, California 91403, United States
  • Research Site
    Thousand Oaks, California 91360, United States
  • Research Site
    Upland, California 91786, United States
  • Research Site #1
    Whittier, California 90603, United States
  • Research Site #2
    Whittier, California 90603, United States
  • Research Site
    Arvada, Colorado 80002, United States
  • Research Site
    Denver, Colorado 80230, United States
  • Research Site
    Westminster, Colorado 80031, United States
  • Research Site
    New Haven, Connecticut 06511, United States
  • Research Site
    Stamford, Connecticut 06902, United States
  • Research Site
    Waterbury, Connecticut 06708, United States
  • Research Site
    Bradenton, Florida 34209, United States
  • Research Site
    Brandon, Florida 33511, United States
  • Research Site
    Cooper City, Florida 33024, United States
  • Research Site #1
    Coral Gables, Florida 33134, United States
  • Research Site #2
    Coral Gables, Florida 33134, United States
  • Research Site
    Coral Springs, Florida 33065, United States
  • Research Site
    Coral Springs, Florida 33071, United States
  • Research Site
    Doral, Florida 33166, United States
  • Research Site
    Fort Myers, Florida 33901, United States
  • Research Site
    Hialeah, Florida 33010, United States
  • Research Site #1
    Hialeah, Florida 33012, United States
  • Research Site #2
    Hialeah, Florida 33012, United States
  • Research Site #3
    Hialeah, Florida 33012, United States
  • Research Site
    Hialeah, Florida 33018, United States
  • Research Site #1
    Hollywood, Florida 33024, United States
  • Research Site #2
    Hollywood, Florida 33024, United States
  • Research Site
    Jacksonville, Florida 32204, United States
  • Research Site #1
    Jacksonville, Florida 32216, United States
  • Research Site #2
    Jacksonville, Florida 32216, United States
  • Research Site
    Lake Worth, Florida 33467, United States
  • Research Site
    Lauderdale Lakes, Florida 33313, United States
  • Research Site
    Miami, Florida 33122, United States
  • Research Site
    Miami, Florida 33125-4141, United States
  • Research Site #1
    Miami, Florida 33126, United States
  • Research Site #2
    Miami, Florida 33126, United States
  • Research Site
    Miami, Florida 33133, United States
  • Research Site
    Miami, Florida 33134, United States
  • Research Site
    Miami, Florida 33135, United States
  • Research Site
    Miami, Florida 33143, United States
  • Research Site
    Miami, Florida 33144, United States
  • Research Site
    Miami, Florida 33145, United States
  • Research Site
    Miami, Florida 33150, United States
  • Research Site
    Miami, Florida 33157, United States
  • Research Site
    Miami, Florida 33165, United States
  • Research Site
    Miami, Florida 33169, United States
  • Research Site #1
    Miami, Florida 33175, United States
  • Research Site #2
    Miami, Florida 33175, United States
  • Research Site
    Miami Beach, Florida 33140, United States
  • Research Site
    Miami Lakes, Florida 33014, United States
  • Research Site
    Miami Lakes, Florida 33016, United States
  • Research Site
    Miami Springs, Florida 33166, United States
  • Research Site
    Pembroke Pines, Florida 33026, United States
  • Research Site
    Pompano Beach, Florida 33060, United States
  • Research Site
    Sweetwater, Florida 33172, United States
  • Research Site
    Tampa, Florida 33604, United States
  • Research Site
    Tampa, Florida 33612, United States
  • Research Site
    Tampa, Florida 33614, United States
  • Research Site
    Atlanta, Georgia 30338, United States
  • Research Site
    Atlanta, Georgia 30342, United States
  • Research Site
    Atlanta, Georgia 30350, United States
  • Research Site #1
    Augusta, Georgia 30909, United States
  • Research Site #2
    Augusta, Georgia 30909, United States
  • Research Site
    Columbus, Georgia 31901, United States
  • Research Site #1
    Columbus, Georgia 31904, United States
  • Research Site #2
    Columbus, Georgia 31904, United States
  • Research Site #1
    Lawrenceville, Georgia 30046, United States
  • Research Site #2
    Lawrenceville, Georgia 30046, United States

Showing the first 100 of 439 sites across 20 countries.

09

References and documents

Publications

  • Chertow GM, Eckardt KU, Sarnak MJ, Winkelmayer WC, Agarwal R, Minga T, Luo W, Burke SK. Safety and Efficacy of Vadadustat for the Treatment of CKD-Related Anemia within and outside the United States. J Am Soc Nephrol. 2025 Oct 1;36(10):1984-1997. doi: 10.1681/ASN.0000000708. Epub 2025 May 13. PubMed 40359056 ↗
  • Natale P, Palmer SC, Jaure A, Hodson EM, Ruospo M, Cooper TE, Hahn D, Saglimbene VM, Craig JC, Strippoli GF. Hypoxia-inducible factor stabilisers for the anaemia of chronic kidney disease. Cochrane Database Syst Rev. 2022 Aug 25;8(8):CD013751. doi: 10.1002/14651858.CD013751.pub2. PubMed 36005278 ↗
  • Chertow GM, Pergola PE, Farag YMK, Agarwal R, Arnold S, Bako G, Block GA, Burke S, Castillo FP, Jardine AG, Khawaja Z, Koury MJ, Lewis EF, Lin T, Luo W, Maroni BJ, Matsushita K, McCullough PA, Parfrey PS, Roy-Chaudhury P, Sarnak MJ, Sharma A, Spinowitz B, Tseng C, Tumlin J, Vargo DL, Walters KA, Winkelmayer WC, Wittes J, Eckardt KU; PRO2TECT Study Group. Vadadustat in Patients with Anemia and Non-Dialysis-Dependent CKD. N Engl J Med. 2021 Apr 29;384(17):1589-1600. doi: 10.1056/NEJMoa2035938. PubMed 33913637 ↗

Study documents

  • Study protocol · Feb 26, 2019
  • Statistical analysis plan · Jan 29, 2020

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

10

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Ran from Dec 2015 to primary completion in Jun 2020, 54 months.

Results were first posted in Jun 2022, 2 years after primary completion. A results delay was requested in Jun 2021.

Of 109 industry-sponsored phase 3 interventional studies under Anemia, half reached primary completion within 22 months of starting (the median), counting those still running; a quarter within 14 and three quarters within 44. This study's 54 months is above that.

Counting every sponsor, half of 167 studies reached it within 24 months; a quarter within 15 and three quarters within 49.

How these figures are worked out, and which studies are left out of them.

Registered
Jan 4, 2016
First posted
Jan 7, 2016
StartActual
Dec 2015
Primary completionActual
Jun 4, 2020
CompletionActual
Jul 31, 2020
Results delay requested
Jun 3, 2021
Results first posted
Jun 27, 2022
Last update
Jun 27, 2022
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Jun 27, 2022, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02648347
Lead sponsor
Akebia Therapeutics
Responsible party
Sponsor
First posted
Jan 7, 2016
Start date
Dec 2015
Primary completion
Jun 4, 2020
Completion
Jul 31, 2020
Results posted
Jun 27, 2022
Last update
Jun 27, 2022

Study contacts

Chief Medical Officer
study director · Akebia Therapeutics

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Jun 2022. You cannot join it, but the record below documents what was studied.

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Discussion

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Studies of the drug tested here: Vadadustat

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