E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Anemia of Chronic kidney disease (CKD) |
Anemia de la enfermedad renal crónica (ERC) |
|
E.1.1.1 | Medical condition in easily understood language |
Decrease of hemoglobin in the blood of patients suffering from kidney disease who require dialysis or not |
Disminución de la hemoglobina en la sangre de los pacientes que padecen enfermedades renales que requieren o no diálisis |
|
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 | 10002272 |
E.1.2 | Term | Anemia |
E.1.2 | System Organ Class | 100000004851 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10064848 |
E.1.2 | Term | Chronic kidney disease |
E.1.2 | System Organ Class | 10038359 - Renal and urinary disorders |
|
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 |
The primary objective of the trial is to assess the safety and efficacy of once daily (QD) dosing of vadadustat for the treatment of pediatric subjects with anemia of Chronic Kidney Disease (CKD) naïve to ESA treatment. |
Evaluar la seguridad y la eficacia de la administración una vez al día de vadadustat en pacientes pediátricos con anemia por NC no tratados previamente con FEE. |
|
E.2.2 | Secondary objectives of the trial |
The secondary objective of the trial is to assess the Pharmacokinetics (PK) and Pharmacodynamics (PD) of vadadustat administered QD dosing in pediatric subjects with anemia of CKD |
El objetivo secundario del ensayo es evaluar la Farmacocinética (PK) y la Farmacodinámica (PD) de vadadustat administrado en dosis QD en sujetos pediátricos con anemia de CKD |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
*Diagnosis of anemia of chronic kidney disease (CKD) *Diagnosis of non-dialysis-dependent (NDD) CKD with an estimated glomerular filtration rate of greater than (>) 10 and less than (<) 60 milliliters/minute/1.73 meters^2 (mL/min/1.73 m^2) or diagnosis of dialysis dependent (DD) CKD *Mean screening hemoglobin (Hb) <10.0 grams/deciliters (g/dL) *Transferrin Saturation ≥ 20% |
*Diagnóstico de anemia de enfermedad renal crónica (ERC) *Diagnóstico de ERC no dependiente de diálisis (NDD) con una tasa de filtración glomerular estimada mayor de (>) 10 y menor de (<) 60 mililitros/minuto/1,73 metros^2 (mL/min/1,73 m^2) o diagnóstico de ERC dependiente de diálisis (DD) *Hemoglobina (Hb) media de cribado <10,0 gramos/decilitros (g/dL) *Saturación de transferrina ≥ 20%. |
|
E.4 | Principal exclusion criteria |
*Anemia due to a cause other than CKD *Active bleeding or recent clinically significant blood loss *History of sickle cell disease, myelodysplastic syndromes, bone marrow fibrosis, hematologic malignancy, myeloma, hemolytic anemia, thalassemia, or pure red cell aplasia *Red Blood Cells transfusion within 4 weeks *Serum albumin level less than 2.5 g/dL *Uncontrolled hypertension *Active malignancy or treatment for malignancy within the past 2 years prior to Screening *Evidence of iron overload or diagnosis of hemochromatosis *Known hypersensitivity to vadadustat or any excipients in vadadustat tablet |
*Anemia debida a una causa distinta de la ERC *Hemorragia activa o pérdida de sangre clínicamente significativa reciente *Historia de anemia de células falciformes, síndromes mielodisplásicos, fibrosis de la médula ósea, neoplasia hematológica, mieloma, anemia hemolítica, talasemia o aplasia pura de células rojas *Transfusión de glóbulos rojos en un plazo de 4 semanas *Nivel de albúmina sérica inferior a 2,5 g/dL *Hipertensión no controlada *Malignidad activa o tratamiento por malignidad en los últimos 2 años antes del cribado *Evidencia de sobrecarga de hierro o diagnóstico de hemocromatosis *Hipersensibilidad conocida a vadadustat o a cualquier excipiente del comprimido de vadadustat |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy endpoints: Mean change in Hb values between Baseline (average pretreatment Hb) and the Primary Evaluation Period (average Hb from Weeks 21 to 28) |
Criterios de valoración de la eficacia: Cambio medio en los valores de Hb entre la línea de base (promedio de Hb antes del tratamiento) y el período de evaluación primaria (promedio de Hb de las semanas 21 a 28) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Efficacy timepoints : Weeks 21 to 28 inclusive |
Puntos de tiempo de eficacia : Semanas 21 a 28 inclusive |
|
E.5.2 | Secondary end point(s) |
Efficacy endpoints : *Time to achieve Hb ≥10.0 g/dL *Proportion of subjects with mean Hb values within the target (≥10.0 to <12.0 g/dL) during the Primary Evaluation Period (Weeks 21 to 28) *Proportion of subjects with mean Hb values within the target (≥10.0 to <12.0 g/dL) during the Extension Period (Weeks 29 to 52) Safety and Tolerability endpoints: *Frequency and severity of AEs, SAEs, and discontinuation from the study due to AEs *Clinically significant changes from Baseline on vital signs, body weight, height, clinical laboratory tests (hematology, serum chemistry, iron indices), and ECG *Adrenal function assessed by adrenocorticotropic hormone (ACTH) stimulation testing and/or morning (AM) cortisol levels PK/PD endpoints: *Determination of plasma concentrations of vadadustat and metabolites for estimation of PK parameters. A population PK (POPPK) model may be constructed and, if so, reported separately. *Changes in serum EPO, reticulocyte count, and Hb as indices of HIF activity Exploratory endpoints: *Mean change from Baseline to Primary Evaluation Period and End of Treatment (EOT) Visit or Early Termination (ET) Visit in Pediatric Quality of Life Inventory™ (PedsQL) 4.0 Generic Core scores for all subjects and/or parent/legal guardian and for PedsQL 3.0 endstage renal disease (ESRD) Module scores in dialysis subjects and/or parent/legal guardian *Change in biomarkers hepcidin and vascular endothelial growth factor (VEGF) |
Criterios de valoración de la eficacia : *Tiempo para lograr una Hb ≥10,0 g/dL *Proporción de sujetos con valores medios de Hb dentro del objetivo (≥10,0 a <12,0 g/dL) durante el periodo de evaluación primaria (semanas 21 a 28) *Proporción de sujetos con valores medios de Hb dentro del objetivo (≥10,0 a <12,0 g/dL) durante el Periodo de Extensión (Semanas 29 a 52) Criterios de valoración de seguridad y tolerabilidad: *Frecuencia y gravedad de los EA, EAS y abandono del estudio debido a EA. *Cambios clínicamente significativos con respecto al inicio del estudio en las constantes vitales, el peso corporal, la altura, las pruebas de laboratorio clínico (hematología, química sérica, índices de hierro) y el ECG. *Función suprarrenal evaluada mediante pruebas de estimulación de la hormona adrenocorticotrópica (ACTH) y/o niveles de cortisol matutino (AM) Criterios de valoración PK/PD: *Determinación de las concentraciones plasmáticas de vadadustat y sus metabolitos para la estimación de los parámetros PK. Puede construirse un modelo de PK poblacional (POPPK) y, si es así, informarse por separado. *Cambios en la EPO sérica, el recuento de reticulocitos y la Hb como índices de la actividad del HIF. Criterios de valoración exploratorios: *Cambio medio desde el inicio hasta el periodo de evaluación primaria y la visita de fin de tratamiento (EOT) o la visita de finalización temprana (ET) en las puntuaciones del núcleo genérico del Pediatric Quality of Life Inventory™ (PedsQL) 4.0 para todos los sujetos y/o los padres/tutores legales y para las puntuaciones del módulo de enfermedad renal terminal (ESRD) del PedsQL 3.0 puntuaciones en sujetos en diálisis y/o padres/tutores legales *Cambio en los biomarcadores hepcidina y factor de crecimiento endotelial vascular (VEGF) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Efficacy endpoints : Weeks 21 to weeks 52 inclusive |
Criterios de valoración de la eficacia : Semanas 21 a 52 inclusive |
|
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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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 | No |
E.8.1.1 | Randomised | No |
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 | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
3 staggered age cohorts (protocol amendment planned after cohort 1 completion) |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
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 |
United States |
France |
Germany |
Hungary |
Italy |
Poland |
Netherlands |
Spain |
|
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
|
|
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 | 5 |
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 |