E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Anemia in Subjects with Incident Dialysis-Dependent Chronic Kidney Disease (DD-CKD) |
Anemia nei soggeti con malattia renale cronica dipendente da dialisi incidente |
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E.1.1.1 | Medical condition in easily understood language |
Decrease of hemoglobin in the blood of patients suffering from end-stage kidney disease who require dialysis |
Diminuzione di emoglobina nel sangue di pazienti affetti da malattia renale allo stadio terminale che necessitano di dialisi |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10076412 |
E.1.2 | Term | Chronic kidney disease stage 5 |
E.1.2 | System Organ Class | 100000004857 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Demonstrate the efficacy and safety of vadadustat compared with darbepoetin alfa for the correction and maintenance of HGB in subjects with anemia secondary to CKD who have recently initiated dialysis treatment for end-stage renal disease. |
Dimostrare l’efficacia e la sicurezza di vadadustat rispetto a darbepoetina per la correzione e il mantenimento dell’HGB in soggetti con anemia secondaria alla malattia renale cronica (chronic kidney disease, CKD) che hanno recentemente iniziato un trattamento con dialisi per malattia renale terminale. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. ≥ 18 years of age 2. Initiated chronic maintenance dialysis (either peritoneal or hemodialysis) for end-stage kidney disease within 16 weeks prior to Screening 3. Mean Screening hemoglobin < 10.0 g/dL |
1. Età ≥18 anni 2. Dialisi cronica di mantenimento (peritoneale o emodialisi) per la malattia renale terminale entro 16 settimane prima dello screening. 3. HGB media allo screening <10,0 g/dl
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E.4 | Principal exclusion criteria |
1. Received more than 1 dose of long-acting (e.g., darbepoetin alfa, methoxy polyethylene glycol-epoetin beta [Mircera, C.E.R.A.]) or 2 doses of short acting eryhropoiesis-stimulating agent (ESA) (e.g., recombinant human erythropoietin [rHuEPO]) within 8 weeks prior to Screening. Subjects may not receive any ESA during the Screening period. 2. Uncontrolled hypertension 3. Severe heart failure at or during screening (New York Heart Association) 4. Acute coronary syndrome (hospitalization for unstable angina or myocardial infarction), urgent coronary revascularisation, hospitalization for Congestive Heart Failure, or stroke within 12 weeks prior to screening 5. Hypersensitivity to darbepoetin or vadadustat, or to any of their excipients |
1. Assunzione di più di 1 dose di ESA a lunga durata d’azione (ad es. darbepoetina alfa, metossi polietilene glicole-epoetina beta [Mircera, C.E.R.A]) o 2 dosi di ESA a breve durata d’azione (ad es. eritropoietina umana ricombinante [recombinant human erythropoietin, rHuEPO]) entro 8 settimane prima dello screening. I soggetti non possono ricevere ESA durante il periodo di screening. 2. Ipertensione incontrollata 3. Grave insufficienza cardiaca allo screening o durante lo screening stesso (classe IV della New York Heart Association) 4. Sindrome coronarica acuta (ricovero per angina instabile, infarto miocardico); intervento chirurgico o percutaneo per malattia coronarica, cerebrovascolare o arteriopatia periferica (aortica o delle estremità inferiori); sostituzione o riparazione valvolare chirurgica o percutanea; tachicardia ventricolare prolungata; ricovero per CHF; o ictus entro 12 settimane prima dello screening o durante lo screening stesso. 5. Ipersensibilità a vadadustat, darbepoetina alfa o qualsiasi loro eccipiente. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Mean change in HGB between Baseline and the primary evaluation period 2. Major adverse cardiovascular events (MACE), defined as all-cause mortality, non-fatal myocardial infarction, or non-fatal stroke |
1. Variazione media dell’HGB tra il basale e il periodo della valutazione primaria 2. MACE, definito come mortalità per tutte le cause, infarto del miocardio non fatale o ictus non fatale. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Baseline visit, week 36 2. From Baseline visit to end of study |
1. Baseline visit, week 36 2. From Baseline visit to end of study |
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E.5.2 | Secondary end point(s) |
Efficacy 1. Mean change in hemoglobin value between Baseline and the secondary evaluation period 2. Proportion of subjects with mean HGB within the target range during the primary evaluation period
Safety 3. AEs and SAEs |
Efficacia 1. Variazione media dell’HGB tra il basale e il periodo della valutazione secondaria 2. Percentuale di soggetti con HGB media entro l’intervallo target durante il periodo della valutazione primaria
Sicurezza 3. Eventi avversi (EA) ed eventi avversi seri (serious adverse event, SAE). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Baseline visit, Week 52 2. Baseline visit, Week 36 3. From Baseline visit to end of study |
1. Baseline visit, Week 52 2. Baseline visit, Week 36 3. From Baseline visit to end of study |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Darbepoetin alfa |
Darbepoetin alfa |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 31 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Brazil |
Mexico |
Russian Federation |
Ukraine |
United States |
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E.8.7 | Trial 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
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LVLS |
Ultima visita dell'utimo paziente |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |