E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
chronic heart failure |
Insuficiencia cardíaca crónica |
|
E.1.1.1 | Medical condition in easily understood language |
chronic heart failure |
Insuficiencia cardíaca crónica |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
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 |
assess the safety of repeat doses of serelaxin in chronic heart failure |
evaluar la seguridad de dosis repetidas de serelaxina administradas en pacientes con insfuciencia cardíaca crónica |
|
E.2.2 | Secondary objectives of the trial |
- assess the incidence rate of adverse events of special interest, indicative of hypersensitivity reactions - assess the safety and tolerability of repeated infusions of serelaxin relative to placebo, in subjects with chronic heart failure -characterize the pharmacokinetics of serelaxin during and after administration of repeated infusions |
-Evaluar la tasa de incidencia de acontecimientos adversos de interés especial, indicativos de reacciones de hipersensibilidad -Evaluar la seguridad y tolerabilidad de infusiones repetidas de serelaxina respecto al placebo, en pacientes con insuficiencia cardíaca crónica. -Caracterizar la farmacocinética de serelaxina durante y después de la administración de infusiones repetidas. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Body weight of ? 160 kg - Subjects with compensated CHF (NYHA Class II ? III) at time of screening with a prior documented history of chronic heart failure - NT-proBNP >300 pg/ml (according to central measurement) at visit 1 - Subjects treated with appropriate and guideline-indicated CHF standard of care - Ability to comply with all requirements, including ability to receive at least a 48 hour infusion plus follow-up time required for each dosing visit. |
-peso corporal de ? 160 kg. .Pacientes con ICC compensada (Clase II ? III de la NYHA) en el momento de la selección con antecedentes documentados previos de insuficiencia cardíaca crónica. -NT-proBNP >300 pg/ml (de acuerdo con la medición central) en la visita 1. -Pacientes tratados con el tratamiento de referencia apropiado e indicado por las guías para la ICC -Capacidad para cumplir con todos los requisitos, incluida la capacidad para recibir al menos una infusión de 48 horas más el tiempo de seguimiento necesario para cada visita de administración. |
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E.4 | Principal exclusion criteria |
- Current acute decompensated HF - Any major solid organ transplant recipient or planned anticipated organ transplant within 1 year - Documented history of untreated ventricular arrhythmia with syncopal episodes, ventricular tachycardia, or ventricular fibrillation without ICD (implantable cardioverter defibrillator) with significant hemodynamic consequences within the 3 months prior to screening - Presence of hemodynamically significant mitral and /or aortic valve disease, except mitral regurgitation secondary to left ventricular dilatation: including significant left ventricular outflow obstruction (e.g., obstructive hypertrophic cardiomyopathy, severe aortic stenosis) - Subjects with severe renal impairment defined as prerandomization eGFR < 30 ml/min/1.73m2 calculated using the sMDRD equation and/or those receiving current or planned dialysis or ultrafiltration |
?IC descompensada aguda actual ?Cualquier receptor de trasplante mayor de órgano sólido o trasplante de órgano planificado anticipado en el plazo de 1 año ?Antecedentes documentados de arritmia ventricular no tratada con episodios de síncope, taquicardia ventricular o fibrilación ventricular sin DCI (desfibrilador cardioversor implantable) con consecuencias hemodinámicas significativas en los 3 meses previos a la selección. ?Presencia de enfermedad de la válvula mitral y/o aórtica hemodinámicamente significativa, excepto regurgitación mitral secundaria a dilatación ventricular izquierda: incluida obstrucción del conducto de salida del ventrículo izquierdo (p. ej., miocardiopatía hipertrófica obstructiva, estenosis aórtica severa) ?Insuficiencia renal severa definida como una TFGe en la prealeatorización <30 ml/min/1,73m2 calculada utilizando la fórmula sMDRD en la visita 1 y/o pacientes que reciban diálisis actual o planificada o ultrafiltración |
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E.5 End points |
E.5.1 | Primary end point(s) |
Percentage of participants with chronic heart failure who develop anti-serelaxin antibodies following repeat administration of IV continuous infusions of serelaxin up to 48 hours |
Proporción de pacientes con insuficiencia cardíaca crónica (ICC) que desarrollen anticuerpos anti-serelaxina tras la administración repetida de infusiones i.v. continuadas de serelaxina administradas durante un período de hasta 48 horas |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
- Percentage of participants with chronic heart failure who develop anti-serelaxin antibodies - Antibody levels in subjects with chronic heart failure who develop anti-serelaxin antibodies (neutralizing, non-neutralizing or both) - Number of patients with adverse events - Percentage of participants with chronic heart failure who develop anti-serelaxin antibodies neutralizing or non-neutralizing - Pharmacokinetics of RLX030: Area under the plasma concentration time curve from time zero up to 48 hours post dose (AUC 0-48), actual concentrations over time, - Pharmacokinetics of RLX030: Cmax steady state (Cmaxss) concentration, clearance of serelaxin |
-Porcentaje de participantes con insuficiencia cardíaca crónica que desarrollan anticuerpos anti-serelaxin - Los niveles de anticuerpos en sujetos con insuficiencia cardíaca crónica que desarrollan anticuerpos anti-serelaxin (neutralizantes, no neutralizantes o ambos) - Número de pacientes con eventos adversos - Porcentaje de participantes con insuficiencia cardíaca crónica que desarrollan anticuerpos neutralizantes anti-serelaxin o no neutralizantes - Farmacocinética de RLX030: Área bajo la curva de concentración plasmática desde el tiempo cero hasta 48 horas después de la dosis (AUC 0-48) - Farmacocinética de RLX030: constante estado (Cmaxss) Cmax |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- after a single infusion (Week 4), two infusions (Week 8) or three infusions (Week 12) of serelaxin. - at any time following 3 repeated infusions and at Week 4, Week 8 and Week 12. - 16 Weeks - at any time following 3 repeated infusions and at Week 4, Week 8 and Week 12. - pre-infusion and 8, 24 and 48 hours post each infusion. - 48 hours after every infusion |
-Después de una sola infusión (Semana 4), dos infusiones (Semana 8) o tres infusiones (Semana 12) de serelaxin. - En cualquier momento después de 3 perfusiones repetidas y en la semana 4, semana 8 y semana 12. - 16 Semanas - En cualquier momento después de 3 perfusiones repetidas y en la semana 4, semana 8 y semana 12. - Pre-infusión y 8, 24 y 48 horas después de cada infusión. - 48 horas después de cada infusión |
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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 | No |
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 | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
|
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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) | No |
E.8.2.2 | Placebo | Yes |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 32 |
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 |
Australia |
Finland |
France |
Germany |
Italy |
Norway |
Romania |
Russian Federation |
Spain |
Sweden |
Turkey |
United Kingdom |
United States |
|
E.8.7 | Trial has a data monitoring committee | No |
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
|
LPLV |
Última visita del último paciente |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 4 |