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Completed

NCT Number: NCT02865850

Efficacy and Safety Study to Evaluate Vadadustat for the Correction or Maintenance Treatment of Anemia in Participants With Incident Dialysis-dependent Chronic Kidney Disease (DD-CKD)

A multicenter, randomized, open-label, active-controlled Phase 3 study for the correction or maintenance treatment of anemia in participants with incident dialysis-dependent chronic kidney disease (DD-CKD).

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Key information

Conditions

Anemia Chronic Disease Dialysis-dependent Chronic Kidney Disease Disease Attributes Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Hematologic Diseases Hemic and Lymphatic Diseases Kidney Diseases Male Urogenital Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Renal Insufficiency Renal Insufficiency, Chronic Urogenital Diseases Urologic Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Research Site, Bahía Blanca, Buenos Aires, Argentina

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About this study

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 or maintenance treatment in participants with anemia secondary to chronic kidney disease who have recently initiated dialysis treatment for end-stage renal disease.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • ≥18 years of age
  • Initiated chronic maintenance dialysis (either peritoneal or hemodialysis) for end-stage kidney disease within 16 weeks prior to Screening
  • Mean Screening hemoglobin between 8.0 and <11.0 grams per deciliter (g/dL) (inclusive)
  • Serum ferritin ≥100 nanograms per deciliter (ng/mL) and TSAT ≥20% during Screening

Exclusion criteria

  • Anemia due to a cause other than chronic kidney disease or participants with active bleeding or recent blood loss
  • Red blood cells transfusion within 8 weeks prior to randomization
  • Anticipated to recover adequate kidney function to no longer require dialysis
  • Uncontrolled hypertension
  • Severe heart failure at Screening (New York Heart Association Class IV)
  • Acute coronary syndrome (hospitalization for unstable angina, 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 congestive heart failure; or stroke within 12 weeks prior to or during Screening.
  • Participants meeting the criteria of erythropoiesis-stimulating agent resistance within 8 weeks prior to or during Screening defined as follows
  • epoetin: > 7700 units/dose three times per week or >23,000 units per week
  • Darbepoetin alfa: >100 micrograms per week (mcg/week)
  • methoxy polyethylene glycol-epoetin beta: >100 micrograms (mcg) every other week or >200 mcg/month
  • Hypersensitivity to Vadadustat, Darbepoetin alfa or any of their excipients

Treatment and study plan

Vadadustat

Drug

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

Other names: AKB-6548

darbepoetin alfa

Drug

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. For participants already on Darbepoetin alfa, the initial dosing regimen in the study was based on the prior dosing regimen.

Other names: Aranesp

Primary outcomes

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

    Time frame: Baseline; 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 hemoglobin concentration (<9.5 versus ≥9.5 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.

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

    Time frame: Up to 176 weeks

    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. INNOVATE MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0016 (NCT02865850) and AKB-6548-CI-0017 (NCT02892149). Results and statistical analysis from study AKB-6548-CI-0016 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-0016 and AKB-6548-CI-0017 has been reported under section "Statistical Analysis 2" of this outcome measure.

Secondary outcomes

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

    Time frame: Baseline; 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 hemoglobin 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.

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

    Time frame: Up to 176 weeks

    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. INNOVATE MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0016 (NCT02865850) and AKB-6548-CI-0017 (NCT02892149). Results and statistical analysis from study AKB-6548-CI-0016 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-0016 and AKB-6548-CI-0017 has been reported under section "Statistical Analysis 2" of this outcome measure.

  3. Median Time to First Cardiovascular MACE

    Time frame: Up to 176 weeks

    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. INNOVATE MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0016 (NCT02865850) and AKB-6548-CI-0017 (NCT02892149). Results and statistical analysis from study AKB-6548-CI-0016 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-0016 and AKB-6548-CI-0017 has been reported under section "Statistical Analysis 2" of this outcome measure.

  4. Median Time to First Cardiovascular Death

    Time frame: Up to 176 weeks

    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. INNOVATE MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0016 (NCT02865850) and AKB-6548-CI-0017 (NCT02892149). Results and statistical analysis from study AKB-6548-CI-0016 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-0016 and AKB-6548-CI-0017 has been reported under section "Statistical Analysis 2" of this outcome measure.

  5. Median Time to First All-cause Mortality

    Time frame: Up to 176 weeks

    Only events that were positively adjudicated and confirmed by the EAC were included in the MACE analyses. INNOVATE MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0016 (NCT02865850) and AKB-6548-CI-0017 (NCT02892149). Results and statistical analysis from study AKB-6548-CI-0016 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-0016 and AKB-6548-CI-0017 has been reported under section "Statistical Analysis 2" of this outcome measure.

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

Sponsors and collaborators

Lead sponsor

Akebia Therapeutics

Industry

Registry information

Official study title

Phase 3, Randomized, Open-Label, Active-Controlled Study Evaluating the Efficacy and Safety of Oral Vadadustat for the Correction or Maintenance Treatment of Anemia in Subjects With Incident Dialysis-Dependent Chronic Kidney Disease (DD-CKD) (INNO2VATE - CORRECTION/CONVERSION)

Important dates

Study start
2016
Primary completion
2020
Study completion
2020
First posted
Aug 15, 2016
Registry last updated
Jul 18, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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