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Study Evaluating the Efficacy and Safety of Dose Conversion From a Long-acting Erythropoiesis-stimulating Agent (Mircera®) to Three Times Weekly Oral Vadadustat for the Maintenance Treatment of Anemia in Hemodialysis Subjects

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ClinicalTrials.gov Identifier: NCT04707768
Recruitment Status : Recruiting
First Posted : January 13, 2021
Last Update Posted : November 15, 2021
Sponsor:
Information provided by (Responsible Party):
Akebia Therapeutics

Brief Summary:
This study will be conducted to demonstrate the efficacy and safety of vadadustat administered three times weekly (TIW) compared to a long-acting erythropoiesis-stimulating agent (ESA) (Mircera®) for the maintenance treatment of anemia in hemodialysis participants.

Condition or disease Intervention/treatment Phase
Anemia Associated With Chronic Kidney Disease (CKD) Drug: Vadadustat Drug: Mircera® Phase 3

Detailed Description:

Following randomization, there will be 2 periods during the study:

  • Conversion and Maintenance Period (Weeks 0 to 52): conversion to vadadustat TIW or to remain on Mircera® (Weeks 0 to 20). There will be a primary efficacy evaluation period (Weeks 20 to 26) and a secondary efficacy evaluation period (Weeks 46 to 52).
  • Safety Follow-up Period (Early Termination [ET] and Follow-Up): post-treatment safety follow-up visit (ET/End of Treatment [EOT] +4 weeks) either in person or via telephone.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 450 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized, Open-label, Active-controlled Study Evaluating the Efficacy and Safety of Dose Conversion From a Long-acting Erythropoiesis-stimulating Agent (Mircera®) to Three Times Weekly Oral Vadadustat for the Maintenance Treatment of Anemia in Hemodialysis Subjects
Actual Study Start Date : July 21, 2021
Estimated Primary Completion Date : November 2022
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Anemia Dialysis

Arm Intervention/treatment
Experimental: Vadadustat low dose
Participants previously receiving Mircera® will receive a low dose of vadadustat for up to 52 weeks.
Drug: Vadadustat
oral tablets

Experimental: Vadadustat high dose
Participants previously receiving Mircera® will receive a high dose of vadadustat for up to 52 weeks.
Drug: Vadadustat
oral tablets

Active Comparator: Mircera®
Participants will continue to receive Mircera® for up to 52 weeks.
Drug: Mircera®
intravenous administration




Primary Outcome Measures :
  1. Mean change in hemoglobin (Hb) between Baseline (average pretreatment Hb) and the primary evaluation period (average Hb from Weeks 20 to 26, inclusive) [ Time Frame: Baseline; Weeks 20-26 ]
  2. Number of participants with treatment-emergent non-serious adverse events and treatment-emergent serious adverse events [ Time Frame: up to Week 56 ]

Secondary Outcome Measures :
  1. Mean change in Hb between Baseline (average pretreatment Hb) and the secondary evaluation period (average Hb from Weeks 46 to 52, inclusive) [ Time Frame: Baseline; Weeks 46-52 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • ≥18 years of age
  • Receiving chronic, outpatient in-center hemodialysis three times weekly (TIW) for end-stage kidney disease for at least 12 weeks prior to Screening Visit 1 (SV1)
  • Currently maintained on Mircera® with at least 2 doses received within 8 weeks prior to Screening Visit 2 (SV2)
  • Mean Screening hemoglobin (Hb) between 8.5 and 11.0 grams per deciliter (g/dL) (inclusive), as determined by the average of 2 Hb values measured by the central laboratory at least 4 days apart between SV1 and SV2
  • Serum ferritin ≥100 nanograms per milliliter (ng/mL) and transferrin saturation (TSAT) ≥20% during Screening
  • Folate and vitamin B12 measurements ≥ lower limit of normal during Screening

Exclusion Criteria:

  • Anemia due to a cause other than chronic kidney disease (CKD) (e.g., sickle cell disease, myelodysplastic syndromes, bone marrow fibrosis, hematologic malignancy, myeloma, hemolytic anemia, thalassemia, or pure red cell aplasia)
  • Clinically meaningful bleeding event in opinion of Investigator within 8 weeks prior to Baseline
  • Red blood cell (RBC) transfusion within 8 weeks prior to Baseline
  • Having received any doses of darbepoetin alfa (Aranesp®) within 4 weeks prior to Baseline
  • Having received any doses of epoetin alfa (Epogen®) within 1 week prior to Baseline
  • Anticipated to discontinue hemodialysis during the study
  • Judged by the Investigator that the participant is likely to need rescue therapy (erythropoiesis-stimulating agent [ESA] administration or RBC transfusion) immediately after enrollment in the study
  • History of chronic liver disease (e.g., chronic infectious hepatitis, chronic autoimmune liver disease, cirrhosis or fibrosis of the liver)
  • Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT), alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT), or total bilirubin >2 x upper limit of normal (ULN) during Screening. Participants with a history of Gilbert's syndrome are not excluded.
  • Current uncontrolled hypertension as determined by the Investigator that would contraindicate the use of an ESA
  • 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 (HF) or New York Heart Association Class IV HF, or stroke within 12 weeks prior to or during Screening
  • History of new, active or recurrent malignancy within 2 years prior to and during Screening or currently receiving treatment or suppressive therapy for cancer. Participants with treated basal cell carcinoma of skin, curatively resected squamous cell carcinoma of skin, or treated cervical carcinoma in situ are not excluded.
  • History of deep vein thrombosis or pulmonary embolism within 12 weeks prior to or during Screening
  • History of hemosiderosis or hemochromatosis
  • History of prior organ transplantation (participants with a history of failed kidney transplant or corneal transplants are not excluded)
  • Scheduled organ transplant from a living donor and participants on the kidney transplant wait-list who are expected to receive a transplant within 6 months
  • History of a prior hematopoietic stem cell or bone marrow transplant (stem cell therapy for knee arthritis is not excluded)
  • Known hypersensitivity to vadadustat, Mircera®, or any of their excipients
  • Use of an investigational medication or participation in an investigational study within 30 days or 5 half-lives of the investigational medication (whichever is longer), prior to Screening (participants may participate in another concurrent study only if that study is a non-interventional, observational investigation)
  • Current exposure to any hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor or prior exposure to vadadustat
  • Participants with bilateral native nephrectomy
  • Noncompliance with dialysis session attendance defined as missing more than 1 dialysis session within 8 weeks prior to Baseline
  • Active Severe Acute Respiratory Syndrome-Related Coronavirus (SARS CoV-2) during Screening
  • Females who are pregnant or breastfeeding during Screening or are planning to become pregnant and breastfeeding during the study period, and for 30 days after the final study drug administration
  • Women of childbearing potential who are unable or unwilling to use 2 acceptable methods of contraception starting at Screening, throughout the study period and for 45 days after the final study drug administration. Acceptable methods of contraception include (a.) established use of oral, injected, or implanted hormonal methods of contraception; (b.) placement of an intrauterine device or intrauterine system; (c.) barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.
  • Female participants of childbearing potential who plan to donate ova during the study, and for 30 days after the last dose of study drug
  • Non-vasectomized male participants who are unable or unwilling to use an acceptable method of contraception from time of first dose of study drug until 30 days after the last dose of the study drug
  • Male participants who plan to donate sperm during the study and for at least 30 days after the last dose of study drug
  • Any other reason, which in the opinion of the Investigator, would make the participant not suitable for participation in the study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04707768


Contacts
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Contact: Akebia Therapeutics 617-844-6128 trials@akebia.com

Locations
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Sponsors and Collaborators
Akebia Therapeutics
Investigators
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Study Director: Chief Medical Officer Akebia Therapeutics Inc.
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Responsible Party: Akebia Therapeutics
ClinicalTrials.gov Identifier: NCT04707768    
Other Study ID Numbers: AKB-6548-CI-0039
First Posted: January 13, 2021    Key Record Dates
Last Update Posted: November 15, 2021
Last Verified: November 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Akebia Therapeutics:
Anemia
Chronic Kidney Disease
CKD
Hemodialysis
Vadadustat
Erythropoiesis-stimulating agent (ESA)
Additional relevant MeSH terms:
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Kidney Diseases
Renal Insufficiency, Chronic
Anemia
Hematologic Diseases
Urologic Diseases
Renal Insufficiency