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)

NCT02865850 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: AKB-6548-CI-00162016-000838-21
• Study Type: interventional
• Target: 369
• Locations: 11 countries
• Sites: 118

Brief Summary

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).

Conditions

Anemia; Dialysis-Dependent Chronic Kidney Disease

Keywords

Vadadustat; AKB-6548; anemia; chronic kidney disease; CKD; chronic renal insufficiency; renal impairment; erythropoietin; kidney; renal; oral anemia treatment; hemoglobin; hypoxia-inducible factor; HIF; efficacy; safety; phase 3; cardiovascular

Outcome Measures

Primary Outcomes (2)

• 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 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.

  Baseline; Weeks 24 to 36

• 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. 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.

  Up to 176 weeks

Secondary Outcomes (5)

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

  Baseline; Weeks 40 to 52

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

  Up to 176 weeks

• Median Time to First Cardiovascular MACE

  Up to 176 weeks

• Median Time to First Cardiovascular Death

  Up to 176 weeks

• Median Time to First All-cause Mortality

  Up to 176 weeks

Other Outcomes (10)

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

  Weeks 24 to 36

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

  Weeks 24 to 36

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

  Weeks 40 to 52

Study Arms (2)

Vadadustat

EXPERIMENTAL

Drug: Vadadustat

Darbepoetin alfa

ACTIVE COMPARATOR

Drug: Darbepoetin alfa

Interventions

Vadadustat DRUG

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

Also known as: AKB-6548

Vadadustat

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.

Also known as: Aranesp

Darbepoetin alfa

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥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

You may not qualify if:

• 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

Sponsors & Collaborators

• Akebia Therapeutics: lead

Study Sites (118)

Research Site

Huntsville, Alabama, 35805, United States

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Mesa, Arizona, 85210, United States

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Anaheim, California, 92801, United States

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Canyon Country, California, 91387, United States

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Downey, California, 90240, United States

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Glendale, California, 91204, United States

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Granada Hills, California, 91344, United States

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La Mesa, California, 91942, United States

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Long Beach, California, 92886, United States

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Los Angeles, California, 90022, United States

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Montebello, California, 90640, United States

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Monterey Park, California, 91754, United States

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Newhall, California, 91321, United States

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Northridge, California, 91324, United States

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Northridge, California, 91324, United States

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Riverside, California, 92503, United States

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Riverside, California, 92505, United States

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Sacramento, California, 95825, United States

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San Diego, California, 92115, United States

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San Dimas, California, 91773, United States

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Whittier, California, 90603, United States

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Arvada, Colorado, 80002, United States

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Westminster, Colorado, 80031, United States

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Stamford, Connecticut, 06902, United States

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Coral Gables, Florida, 33134, United States

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Coral Springs, Florida, 33071, United States

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Lauderdale Lakes, Florida, 33313, United States

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Miami, Florida, 33125, United States

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Miami, Florida, 33150, United States

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Miami Beach, Florida, 33140, United States

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Winter Park, Florida, 32789, United States

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Augusta, Georgia, 30904, United States

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Columbus, Georgia, 31904, United States

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Lawrenceville, Georgia, 30046, United States

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Statesboro, Georgia, 30458, United States

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Meridian, Idaho, 83642, United States

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Takoma Park, Maryland, 20912, United States

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Roseville, Michigan, 48066, United States

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Kansas City, Missouri, 64111, United States

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Albuquerque, New Mexico, 87109, United States

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Astoria, New York, 11102, United States

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Winston-Salem, North Carolina, 27103, United States

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Philadelphia, Pennsylvania, 19106, United States

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Chattanooga, Tennessee, 37408, United States

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Chattanooga, Tennessee, 37408, United States

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Knoxville, Tennessee, 37923, United States

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Nashville, Tennessee, 37205, United States

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Arlington, Texas, 76015, United States

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El Paso, Texas, 79935, United States

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Houston, Texas, 77054, United States

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Houston, Texas, 77099, United States

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San Antonio, Texas, 78212-4740, United States

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San Antonio, Texas, 78229, United States

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Hampton, Virginia, 23666, United States

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Bahía Blanca, Buenos Aires, B8001HXM, Argentina

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Ciudad Autonoma Buenos Aires, Buenos Aires, C1181ACH, Argentina

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Junín, Buenos Aires, 6000, Argentina

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Pergamino, Buenos Aires, B2700CPM, Argentina

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Temperley, Buenos Aires, 1834, Argentina

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Corrientes, 3400, Argentina

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Córdoba, 5000, Argentina

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Salta, A4400AXO, Argentina

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San Luis, 5700, Argentina

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Fortaleza, Ceará, 60430-370, Brazil

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Belo Horizonte, Minas Gerais, 30150-221, Brazil

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Juiz de Fora, Minas Gerais, 36036-330, Brazil

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Curitiba, Paraná, 80010-030, Brazil

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Maringá, Paraná, 87060-040, Brazil

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Canoas, Rio Grande do Sul, 92425-900, Brazil

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Passo Fundo, Rio Grande do Sul, 99010-080, Brazil

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Porto Alegre, Rio Grande do Sul, 90035-074, Brazil

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Porto Alegre, Rio Grande do Sul, 90035-903, Brazil

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Joinville, Santa Catarina, 89202-050, Brazil

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Santo André, São Paulo, 09090-790, Brazil

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São Bernardo do Campo, São Paulo, 09715-090, Brazil

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São Paulo, São Paulo, 04039-000, Brazil

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Villingen-Schwenningen, Baden-Wurttemberg, 78054, Germany

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Rostock, Mecklenburg-Vorpommern, 18057, Germany

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Düsseldorf, North Rhine-Westphalia, 40210, Germany

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San Giovanni Rotondo, Foggia, 71013, Italy

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Genova, 16132, Italy

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Lecco, 23900, Italy

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Napoli, 80138, Italy

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Pavia, 27100, Italy

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Roma, 168, Italy

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Siena, 53100, Italy

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Zapopan, Jalisco, 45030, Mexico

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Morelia, Michoacán, 58260, Mexico

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Culiacán, Sinaloa, 80230, Mexico

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Golub-Dobrzyń, 87-400, Poland

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Lodz, 90-153, Poland

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Lodz, 92-213, Poland

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Leiria, 2400-441, Portugal

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Loures, 2674-514, Portugal

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Kemerovo, 650066, Russia

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Krasnoyarsk, 660022, Russia

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Moscow, 125466, Russia

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Saint Petersburg, 197022, Russia

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Saint Petersburg, 197110, Russia

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Saint Petersburg, 198205, Russia

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Saint Petersburg, 199004, Russia

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Chuncheon, Gangwon-do, 200-702, South Korea

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Seongnam-si, Gyeonggi-do, 13496, South Korea

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Busan, 47392, South Korea

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Seoul, 6591, South Korea

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Seoul, 7345, South Korea

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Brovary, 7400, Ukraine

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Cherkassy, 18009, Ukraine

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Dnipro, 49005, Ukraine

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Ivano-Frankivsk, 76008, Ukraine

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Kharkiv, 61037, Ukraine

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Kyiv, 2125, Ukraine

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Mykolaiv, 54058, Ukraine

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Ternopil, 46002, Ukraine

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Uzhhorod, 88018, Ukraine

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Vinnytsia, 21018, Ukraine

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Zaporizhzhia, 69600, Ukraine

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Zhytomyr, 10002, Ukraine

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Related Publications (4)

• 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.

  PMID: 40359056 DERIVED

• Sarnak MJ, Agarwal R, Boudville N, Chowdhury PCP, Eckardt KU, Gonzalez CR, Kooienga LA, Koury MJ, Ntoso KA, Luo W, Parfrey PS, Vargo DL, Winkelmayer WC, Zhang Z, Chertow GM. Vadadustat for treatment of anemia in patients with dialysis-dependent chronic kidney disease receiving peritoneal dialysis. Nephrol Dial Transplant. 2023 Sep 29;38(10):2358-2367. doi: 10.1093/ndt/gfad074.

  PMID: 37096396 DERIVED

• 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.

  PMID: 36005278 DERIVED

• Eckardt KU, Agarwal R, Aswad A, Awad A, Block GA, Bacci MR, Farag YMK, Fishbane S, Hubert H, Jardine A, Khawaja Z, Koury MJ, Maroni BJ, Matsushita K, McCullough PA, Lewis EF, Luo W, Parfrey PS, Pergola P, Sarnak MJ, Spinowitz B, Tumlin J, Vargo DL, Walters KA, Winkelmayer WC, Wittes J, Zwiech R, Chertow GM. Safety and Efficacy of Vadadustat for Anemia in Patients Undergoing Dialysis. N Engl J Med. 2021 Apr 29;384(17):1601-1612. doi: 10.1056/NEJMoa2025956.

  PMID: 33913638 DERIVED

MeSH Terms

Conditions

Anemia; Renal Insufficiency, Chronic; Renal Insufficiency

Interventions

vadadustat; Darbepoetin alfa

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Erythropoietin; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Proteins; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Clinical Trial Information Desk
• Organization: Akebia Therapeutics, Inc.

trials@akebia.com

+1 617-844-6128

Study Officials

• Chief Medical Officer

  Akebia Therapeutics Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Sponsor was blinded during the study
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 8, 2016
• First Posted: August 15, 2016
• Study Start: July 1, 2016
• Primary Completion: January 31, 2020
• Study Completion: March 30, 2020
• Last Updated: July 18, 2022
• Results First Posted: July 18, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

PT (2); UA (12); US (54); DE (3); RU (7); PL (3); BR (13); KR (5); ME (3); IT (7); AR (9)