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 |
To demonstrate the efficacy and safety of vadadustat compared to darbepoetin alfa for the maintenance treatment of anemia in subjects with DD-CKD. |
Dimostrare l’efficacia e la sicurezza di vadadustat rispetto a darbepoetina alfa per il trattamento di mantenimento dell’anemia nei soggetti affetti da malattia renale cronica dialisi dipendente (Dialysis-Dependent Chronic Kidney Disease, DD-CKD). |
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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. Receiving chronic maintenance dialysis (either peritoneal or hemodialysis) for end-stage kidney disease for at least 12 weeks prior to Screening 3. Currently maintained on ESA therapy, with the last dose received within 8 weeks prior to Screening 4. Mean screening Hb between 8.0 and 11.0 g/dL (inclusive) in the US and between 9.0 and 12.0 g/dL (inclusive) outside of the US, as determined by the average of 2 Hb values measured by the central laboratory during Screening. |
1. Età ≥18 anni 2. Devono essersi sottoposti a dialisi cronica di mantenimento (peritoneale o emodialisi) per la malattia renale terminale per almeno 12 settimane prima dello screening. 3. Attualmente sottoposti a terapia ESA di mantenimento, con l’ultima dose ricevuta nelle 8 settimane precedenti lo screening 4. Valore di HGB medio compreso tra 8,0 e 11,0 g/dl (inclusi) negli USA e tra 9,0 e 12,0 g/dl (inclusi) al di fuori degli USA, determinato dalla media di 2 valori di HGB misurati dal laboratorio centrale durante lo screening. |
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E.4 | Principal exclusion criteria |
1. Uncontrolled hypertension 2. Severe heart failure (HF) during Screening (New York Heart Association Class IV) 3. 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 HF, or stroke within 12 weeks prior to or during Screening. 4. Hypersensitivity to vadadustat, darbepoetin alfa, or any of their excipients |
1. Ipertensione incontrollata 2. Grave insufficienza cardiaca allo screening o durante lo screening stesso (classe IV della New York Heart Association) 3. Sindrome coronarica acuta (ricovero per angina instabile o 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 HF o ictus entro 12 settimane dallo screening o durante lo screening stesso. 4. Ipersensibilità a vadadustat, darbepoetina alfa o qualsiasi loro eccipiente. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Mean change in Hb between Baseline (mean pretreatment Hb) and the primary evaluation period |
Variazione media nel valore dell'HGB tra il basale (HGB media pretrattamento) e il periodo della valutazione primaria |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline Visit, Week 36 |
Baseline Visit, Week 36 |
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E.5.2 | Secondary end point(s) |
Efficacy 1. Mean change in Hb value between Baseline and the secondary evaluation period 2. Proportion of subjects with mean Hb 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. Baseline to end of study |
1. Baseline visit, Week 52 2. Baseline visit, Week 36 3. Baseline 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 |
|
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 | 48 |
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 |
Australia |
Brazil |
Canada |
Israel |
Korea, Republic of |
Mexico |
Russian Federation |
Serbia |
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
|
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 | 5 |
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 | 6 |
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 |