E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Anemia in chronic kidney disease patients not on dialysis |
ANEMIA EN SUJETOS CON ENFERMEDAD RENAL CRÓNICA NO DEPENDIENTE DE DIÁLISIS |
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E.1.1.1 | Medical condition in easily understood language |
Decrease of hemoglobin in the blood of patients suffering from progressive loss in kidney function |
Disminución de la hemoglobina en la sangre de pacientes que sufren de pérdida progresiva de la función renal |
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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 | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10076411 |
E.1.2 | Term | Chronic kidney disease stage 4 |
E.1.2 | System Organ Class | 100000004857 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10076410 |
E.1.2 | Term | Chronic kidney disease stage 3 |
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 maintenance treatment of anemia in subjects with NDD-CKD after conversion from current ESA therapy |
Demostrar la eficacia y seguridad de vadadustat en comparación con darbepoetina alfa en el tratamiento de mantenimiento de la anemia en sujetos con NDD-CKD después de la conversión de la terapia actual con un ESA. |
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E.2.2 | Secondary objectives of the trial |
Not Applicable |
no aplicable |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. ≥ 18 years of age 2. Diagnosis of CKD with an eGFR ≤ 60mL/min/1.73 m² at Screening and not expected to start dialysis within 6 months of Screening 3. Currently maintained on ESA therapy, with the last dose received within 8 weeks prior to Screening 4. Mean Screening HGB 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 |
1. ≥ 18 años de edad 2. Diagnóstico de nefropatía crónica con eGFR ≤ 60 ml/min/1.73 m2 sin inicio de diálisis previsto en los 6 meses siguientes a la selección 3. Actualmente en tratamiento con un ESA, habiendo recibido la última dosis en el lapso de las 8 semanas previas a la Selección 4. Hgb media en la Selección entre 8.0 y 11.0 g/dl (inclusive) en EE. UU. y entre 9.0 y 12.0 g/dl (inclusive) fuera de EE. UU. |
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E.4 | Principal exclusion criteria |
1. Uncontrolled hypertension 2. Severe heart failure at Screening (New York Association Class IV) 3. Acute coronary syndrome (hospitalization for unstable angina or myocardial infarction), urgent coronary revascularisation, hospitalization for Congestive Heart Failure (CHF), or stroke within 12 weeks prior to Screening 4. Hypersensitivity to darbepoetin or vadadustat, or to any of their excipients |
1. Hipertensión no controlada 2. Insuficiencia cardíaca grave en la selección (clase IV de la Asociación Cardíaca de Nueva York) 3. Síndrome coronario agudo (hospitalización debida a angina inestable o infarto del miocardio), revascularización coronaria de urgencia, hospitalización debida a CHF o accidente cerebrovascular en las 12 semanas previas a la Selección 4. Hipersensibilidad a darbepoetina o vadadustat, o a cualquiera de sus excipientes |
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E.5 End points |
E.5.1 | Primary end point(s) |
Mean change in hemoglobin between baseline and the primary evaluation period |
Cambio medio en la Hgb entre el valor inicial y el periodo de evaluación principal |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline visit, Week 36 |
Visita basal, Semana 36 |
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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. Major adverse cardiovascular events (MACE), defined as all-cause mortality, non-fatal myocardial infarction, or non-fatal stroke 4. Individual components of MACE 5. AEs and SAEs |
Eficacia 1. Cambio medio en la Hgb entre el valor inicial y el periodo de evaluación secundario 2. Proporción de sujetos con la media de la Hgb dentro del intervalo objetivo durante el periodo de evaluación principal
Seguridad 3. MACE, definidos como mortalidad por cualquier causa, infarto de miocardio no mortal o accidente cerebrovascular no mortal 4. Componentes individuales de los MACE 5. Eventos adversos (EA) y eventos adversos serios (EAS) |
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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 4. Baseline to end of study 5. Baseline to end of study |
1. Visita basal, semana 52 2. Visita basal, semana 36 3. inicio al final del estudio 4. inicio al final del estudio 5. inicio al final del estudio |
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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 | No |
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 | 14 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 93 |
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 | No |
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 |
Colombia |
Israel |
Japan |
Korea, Republic of |
Mexico |
Russian Federation |
South Africa |
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 ultimo paciente |
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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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |