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    Summary
    EudraCT Number:2019-004851-36
    Sponsor's Protocol Code Number:404-201-00012
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2020-10-22
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2019-004851-36
    A.3Full title of the trial
    Phase 3b, Randomized, Open-label, Active-controlled Trial Evaluating the Efficacy and Safety of Oral Vadadustat Once Daily (QD) and Three Times Weekly (TIW) for the Maintenance Treatment of Anemia in Hemodialysis Subjects Converting from Erythropoiesis-Stimulating Agents (ESAs)
    Studio di fase 3b, randomizzato, in aperto, con controllo attivo per valutare l’efficacia e la sicurezza di vadadustat orale una volta al giorno (QD) e tre volte alla settimana (TIW) per il trattamento di mantenimento dell’anemia in soggetti sottoposti a emodialisi dopo conversione dalla terapia con agenti stimolanti l’eritropoiesi (ESA)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study to evaluate the effectiveness and safety of a study drug called vadadustat which may be used in the maintenance treatment of anemia for hemodialysis participants, after they've converted from ESA therapy.
    Studio per valutare l’efficacia e la sicurezza del farmaco in studio denominato vadadustat che può essere utilizzato per il trattamento di mantenimento dell’anemia in soggetti sottoposti a emodialisi dopo conversione dalla terapia con agenti stimolanti l’eritropoiesi (ESA)
    A.3.2Name or abbreviated title of the trial where available
    Modify
    Modify
    A.4.1Sponsor's protocol code number404-201-00012
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorOtsuka Pharmaceutical Development and Commercialization, Inc
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportOtsuka Pharmaceutical (OPDC)
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationMedpace
    B.5.2Functional name of contact pointClinical Trial Information
    B.5.3 Address:
    B.5.3.1Street Addressul. Zwirki i Wigury 16C
    B.5.3.2Town/ cityWarszawa
    B.5.3.3Post code02-092
    B.5.3.4CountryPoland
    B.5.4Telephone number00000000000000
    B.5.5Fax number00000000000000
    B.5.6E-mailregsubmissions@medpace.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameDarbepoetina alfa
    D.3.2Product code [Darbepoetina alfa]
    D.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    Subcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNDARBEPOETIN ALFA
    D.3.9.1CAS number 209810-58-2
    D.3.9.2Current sponsor codeDarbepoetina alfa
    D.3.9.4EV Substance CodeSUB12486MIG
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameVadadustat
    D.3.2Product code [AKB-6548]
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNVADADUSTAT
    D.3.9.1CAS number 1000025-07-9
    D.3.9.2Current sponsor codeAKB-6548
    D.3.9.4EV Substance CodeSUB186819
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number450
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 3
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameDarbepoetina alfa
    D.3.2Product code [Darbepoetina alfa]
    D.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    Subcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNDARBEPOETINA ALFA
    D.3.9.1CAS number 209810-58-2
    D.3.9.2Current sponsor codeDarbepoetina alfa
    D.3.9.4EV Substance CodeSUB12486MIG
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 4
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameVadadustat
    D.3.2Product code [AKB-6548]
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNVADADUSTAT
    D.3.9.1CAS number 1000025-07-9
    D.3.9.2Current sponsor codeAKB-6548
    D.3.9.4EV Substance CodeSUB186819
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number150
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 5
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameDarbepoetina alfa
    D.3.2Product code [Darbepoetina alfa]
    D.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    Subcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNDARBEPOETINA ALFA
    D.3.9.1CAS number 209810-58-2
    D.3.9.2Current sponsor codeDarbepoetina alfa
    D.3.9.4EV Substance CodeSUB12486MIG
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number40
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 6
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameDarbepoetina alfa
    D.3.2Product code [Darbepoetina alfa]
    D.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    Subcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNDARBEPOETINA ALFA
    D.3.9.1CAS number 209810-58-2
    D.3.9.2Current sponsor codeDarbepoetina alfa
    D.3.9.4EV Substance CodeSUB12486MIG
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Anemia of Chronic kidney disease (CKD)
    Anemia da malattia renale cronica
    E.1.1.1Medical condition in easily understood language
    Decrease of hemoglobin in the blood of patients suffering from kidney disease who require dialysis
    Diminuzione dell' emoglobina nel sangue di pazienti affetti da patologia renale che necessitano di dialisi
    E.1.1.2Therapeutic area Diseases [C] - Blood and lymphatic diseases [C15]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10002272
    E.1.2Term Anemia
    E.1.2System Organ Class 100000004851
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 23.1
    E.1.2Level LLT
    E.1.2Classification code 10076412
    E.1.2Term Chronic kidney disease stage 5
    E.1.2System Organ Class 100000004857
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 23.1
    E.1.2Level LLT
    E.1.2Classification code 10076411
    E.1.2Term Chronic kidney disease stage 4
    E.1.2System Organ Class 100000004857
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective of the trial is to demonstrate the efficacy and safety of vadadustat compared to darbepoetin alfa for the maintenance treatment of anemia in hemodialysis subjects after conversion from current ESA therapy
    L’obiettivo primario dello studio è dimostrare l’efficacia e la sicurezza di vadadustat rispetto a darbepoetina alfa per il trattamento di mantenimento dell’anemia in soggetti sottoposti a emodialisi dopo la conversione dall’attuale terapia con ESA
    E.2.2Secondary objectives of the trial
    Not applicable
    Non applicabile
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives

    Pharmacogenomics
    Version: Originale
    Date: 17/01/2020
    Title: Optional pharmacogenomics (PGx) sub study “Human Biological Samples and Data Collected and Stored for Future Use”
    Objectives: please refer to study protocol

    Farmacogenomica
    Versione: Originale
    Data: 17/01/2020
    Titolo: Sottostudio opzionale di farmacogenomica "Campioni biologici umani e dati raccolti e conservati per uso futuro"
    Obiettivi: si riferisca per favore al protocollo di studio
    E.3Principal inclusion criteria
    1) = 18 years of age.
    2) Receiving chronic, outpatient TIW in-center hemodialysis for endstage renal disease for at least 12 weeks prior to Screening.
    3) Hemodialysis adequacy as indicated by single-pool Kt/Vurea = 1.2 using the most recent historical measurement within 8 weeks prior to or during Screening.
    4) Use of any approved ESA for at least the 8 weeks prior to Screening Visit 2.
    5) Two Hb values, at least 4 days apart, measured by the central laboratory during Screening within the following prespecified ranges:
    a) Hb values between 8.0 and 11.0 g/dL (inclusive) in the US.
    b) Hb values between 9.0 and 12.0 g/dL (inclusive) in Europe.
    6) Serum ferritin = 100 ng/mL and TSAT = 20% during Screening.
    7) Folate and vitamin B12 measurements = lower limit of normal during Screening.
    1) Età =18 anni.
    2) Ricezione di emodialisi cronica in regime ambulatoriale TIW per malattia renale allo stadio terminale da almeno 12 settimane prima dello screening.
    3) Emodialisi adeguata come indicato da un rapporto Kt/Vurea single-pool =1,2 utilizzando la misurazione storica più recente nelle 8 settimane precedenti o durante lo screening.
    4) Uso di qualsiasi ESA approvato per almeno 8 settimane prima della visita di screening 2.
    5) Due valori di Hb misurati dal laboratorio centrale a distanza di almeno 4 giorni durante lo screening entro i seguenti intervalli prespecificati:
    a) valori di Hb tra 8,0 e 11,0 g/dl (estremi inclusi) negli USA;
    b) valori di Hb tra 9,0 e 12,0 g/dl (estremi inclusi) in Europa.
    6) Ferritina sierica =100 ng/ml e saturazione della transferrina (TSAT) =20% durante lo screening.
    7) Valori di folato e vitamina B12 = limite inferiore della norma durante lo screening.
    E.4Principal exclusion criteria
    1) Women of childbearing potential who do not agree to practice 2 different methods of birth control or remain abstinent during the trial and for 30 days after the last dose of investigational medicinal product IMP. If employing birth control, 2 of the following precautions must be used:vasectomy of partner, tubal ligation,vaginal diaphragm, intrauterine device, or birth control. 2)Male subjects who have not had a vasectomy and do not agree to the following: use of an acceptable form of contraception during the study and for 30 days after the last dose of the study drug; to not donate semen during the study and for at least 30 days after the last dose of vadadustat. 3)Women who are breast feeding and/or who have a positive pregnancy test result prior to receiving IMP. 4)Subjects with contraindication to required trial assessment. 5)Subjects who have a medical history or medical findings inconsistent with safety or trial compliance. 6) Anemia due to a cause other than CKD. 7)Subjects meeting cut-off of the following equivalent mean weekly doses calculated over 8 weeks prior to Screening Visit 2: a) Methoxy polyethylene glycol-epoetin beta > 50 µg/week. b) Darbepoetin alfa > 100 µg/week. c) Epoetin analogues > 23000 IU/week.8) Active bleeding or recent blood loss within 8 weeks prior to randomization.9) Red blood cell transfusion within 8 weeks prior to randomization.10) Anticipated to discontinue hemodialysis during the trial. 11) The subject is likely to need rescue therapy immediately after enrollment in the trial. 12) History of chronic liver disease. 13) Aspartate aminotransferase /serum glutamic oxaloacetic transaminase, alanine aminotransferase /serum glutamic pyruvic transaminase, or total bilirubin > 1.5 x upper limit of normal during Screening. The Gilbert's syndrome is not excluded. 14)Current uncontrolled hypertension that would contraindicate the use of an ESA. 15)Acute coronary syndrome, surgical or percutaneous intervention for coronary, cerebrovascular or peripheral artery disease, surgical or percutaneous valvular replacement or repair, sustained ventricular tachycardia, hospitalization for HF or Class IV HF, or stroke within 12 weeks prior to or during Screening. 16) History of new or recurrent malignancy within 2 years prior to and during Screening or currently receiving treatment or suppressive therapy for cancer. Subjects with treated basal cell carcinoma of skin, curatively resected squamous cell carcinoma of skin, or cervical carcinoma in situ are not excluded. 17) History of a new or recurrent episode of deep vein thrombosis or pulmonary embolism within 12 weeks prior to or during Screening. 18) History of hemosiderosis or hemochromatosis. 19) History of prior organ transplantation (failed kidney transplant or corneal transplants are not excluded). 20)Scheduled organ transplant from a living donor and subjects on the kidney transplant wait-list who are expected to receive a transplant within 6 months. 21) History of a prior hematopoietic stem cell or bone marrow transplant (stem cell therapy for knee arthritis is not excluded). 22)Known hypersensitivity to vadadustat, darbepoetin alfa, or any of their excipients. 23) Use of an investigational medication within 30 days or 5 half-lives of the investigational medication, prior to screening or during screening and any prior use of a hypoxia-inducible factor prolyl hydroxylase inhibitor. Subjects may participate in another concurrent trial only if that trial is a non-interventional, observational investigation. 24) Subjects with bilateral native nephrectomy. 25) Treated with probenecid within the 28-day Screening Period prior to randomization or during the study treatment duration. 26)Any other reason would make the subject not suitable for participation in the trial.
    1)Donne in età fertile che non accettano di adottare 2 diversi metodi contraccettivi o praticare l’astinenza durante lo studio e per 30 giorni dopo l’ultima dose del prodotto medicinale sperimentale (IMP).Se si utilizza un metodo contraccettivo, è necessario adottare 2 delle seguenti precauzioni:vasectomia del partner, legatura delle tube,diaframma vaginale,dispositivo intrauterino o anticoncezionale. 2)Soggetti di sesso maschile che non si sono sottoposti a vasectomia e non acconsentono a quanto segue:uso di un metodo contraccettivo accettabile durante lo studio e per 30 giorni dopo l’ultima dose del farmaco in studio;astensione dalla donazione di sperma durante lo studio e per almeno 30 giorni dopo l’ultima dose di vadadustat. 3)Donne che allattano al seno e/o che risultano positive al test di gravidanza prima di ricevere l’IMP. 4)Soggetti con controindicazioni alla valutazione dello studio richiesta. 5)Soggetti che presentano un’anamnesi medica o risultati medici incompatibili con la sicurezza o la conformità allo studio.6)Anemia dovuta a una causa diversa dalla malattia renale cronica.7)Soggetti che soddisfano il cut-off delle seguenti dosi settimanali medie equivalenti calcolate nelle 8 settimane precedenti la visita di screening 2: a)metossipolietilenglicole-epoetina beta >50 µg/settimana; b)darbepoetina alfa >100 µg/settimana; c)Analoghi della epoetina >23.000 UI/settimana. 8)Sanguinamento attivo o perdita di sangue recente nelle 8 settimane precedenti la randomizzazione. 9)Trasfusione di globuli rossi nelle 8 settimane precedenti la randomizzazione.10)Interruzione dell’emodialisi prevista durante lo studio. 11)Il soggetto debba ricorrere a una terapia di soccorso subito dopo l’arruolamento nello studio.12)Anamnesi di malattia epatica cronica.13)Livelli di AST/SGOT, ALT/SGPT o bilirubina totale >1,5 x ULN durante lo screening. La sindrome di Gilbert non è esclusa.14) Ipertensione non controllata in corso che controindica l’uso di un ESA. 5)Sindrome coronarica acuta, intervento chirurgico o percutaneo per coronaropatia, arteriopatia cerebrovascolare o periferica,sostituzione o riparazione valvolare chirurgica o percutanea, tachicardia ventricolare sostenuta,ricovero ospedaliero per insufficienza cardiaca (HF) o HF di Classe IV o ictus entro 12 settimane prima o durante lo screening.16)Anamnesi di neoplasia maligna nuova o ricorrente nei 2 anni precedenti e durante lo screening o attuale somministrazione di un trattamento o una terapia soppressiva per il tumore. I soggetti con carcinoma cutaneo basocellulare trattato, carcinoma cutaneo a cellule squamose sottoposto a resezione con intento curativo o carcinoma cervicale insitu non sono esclusi.17)Anamnesi di un episodio nuovo o ricorrente di trombosi venosa profonda o embolia polmonare nelle 12 settimane precedenti o durante lo screening.18)Anamnesi di emosiderosi o emocromatosi. 19)Anamnesi di precedente trapianto d’organo (trapianto renale non riuscito o trapianti corneali non sono esclusi). 20)Trapianto d’organo programmato da donatore vivente e soggetti in lista d’attesa per un trapianto renale che si prevede riceveranno un trapianto entro 6 mesi. 21)Anamnesi di un precedente trapianto di cellule staminali ematopoietiche o di midollo osseo (la terapia con cellule staminali per l’artrite del ginocchio non è esclusa). 22)Ipersensibilità nota a vadadustat,darbepoetina alfa o a uno degli eccipienti. 23)Uso di un farmaco sperimentale entro 30 giorni o 5 emivite del farmaco sperimentale prima dello screening o durante lo screening e qualsiasi precedente uso di un inibitore prolil-idrossilasi del fattore inducibile dall’ipossia.I soggetti possono partecipare a altro studio concomitante osservazionale non interventistico. 24)Soggetti con nefrectomia nativa bilaterale. 25)Trattamento con probenecid entro il periodo di screening di 28 giorni prima della randomizzazione o durante il trattamento dello studio.26) Qualsiasi altro motivo che rende il soggetto non idoneo allo studio.
    E.5 End points
    E.5.1Primary end point(s)
    Efficacy endpoints: change in hemoglobin (Hb) between Baseline (average pretreatment Hb) and the primary evaluation period (average Hb from Weeks 20 to 26, inclusive).
    Endpoint di efficacia primari : variazione dell’emoglobina (Hb) tra il basale (Hb media pretrattamento) e il periodo di valutazione primario (Hb media dalla Settimana 20 alla 26, incluse).
    E.5.1.1Timepoint(s) of evaluation of this end point
    weeks 20 to 26 inclusive
    dalla Settimana 20 alla 26, incluse
    E.5.2Secondary end point(s)
    efficacy endpoints: change in Hb value between Baseline and the secondary evaluation period (average Hb from Weeks 46 to 52).
    endpoint di efficacia secondari: variazione nel valore Hb tra il basale e il periodo di valutazione secondario (Hb media dalla Settimana 46 alla 52).
    E.5.2.1Timepoint(s) of evaluation of this end point
    Weeks 46 to 52 inclusive
    dalla Settimana 46 alla 52 incluse
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial3
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned5
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA32
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA Information not present in EudraCT
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Belgium
    Czech Republic
    Hungary
    Italy
    Poland
    Spain
    United States
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    The end of trial date is defined as the last date of contact or the date of final contact attempt from the safety follow-up electronic case report form (eCRF) page for the last subject completing or withdrawing from the trial.
    The trial will be considered completed (end of trial) after all randomized subjects have completed their final trial visit (ET, Week 52/EOT, or Safety Follow-Up.)
    La data di fine studio è definita come la data dell' ultimo contatto o la data dell' ultimo tentativo di contatto dalla pagina del follow-up di safety nella CRF riguardante l'ultimo paziente che ha completato o si è ritirato dallo studio.
    Lo studio sarà considerato completato (fine dello studio) dopo che tutti i soggetti randomizzati avranno completato la loro visita finale dello studio ( ET, settimana 52/EOT o Safety Follow-up).
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months1
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months1
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 120
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 180
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state25
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 90
    F.4.2.2In the whole clinical trial 300
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    None
    Nessuno
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2020-10-16
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-10-14
    P. End of Trial
    P.End of Trial StatusOngoing
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