Descripción del proyecto
Un fármaco para la leucemia se utiliza también contra la insuficiencia cardíaca
El infarto agudo de miocardio (IAM) provoca una disfunción ventricular izquierda y una insuficiencia cardíaca en casi el 50 % de los pacientes. Tras ensayos preclínicos exhaustivos, el proyecto financiado con fondos europeos RITA-MI 2 pretende darle un nuevo uso a un fármaco existente, el rituximab, empleado actualmente contra las neoplasias linfáticas y los trastornos autoinmunitarios, como la artritis reumatoide. El rituximab es un anticuerpo monoclonal que se centra de forma selectiva en linfocitos B maduros que expresan el CD20. La idea consiste en detener o limitar la remodelación cardíaca dañina que ocurre tras un IAM y fomentar la recuperación de la función cardíaca. RITA-MI 2 evaluará los efectos de la reducción de los linfocitos B en pacientes con IAM en un ensayo clínico de fase 2b.
Objetivo
RITA-MI 2 will assess the impact of a novel therapeutic strategy targeting patients’ immune response on the recovery of heart function after myocardial infarction (MI) in a phase 2 clinical trial.
Cardiovascular diseases (CVD) represent a major cause of morbidity and mortality worldwide. Despite important advances in the treatment of acute MI, the occurrence of MI still results in left ventricular dysfunction in up to 50% of patients, which leads to the development of heart failure. Left ventricular dysfunction is the strongest predictor of adverse outcome after acute MI, and is associated with a 3 to 4-fold increase in mortality risk. In Westernised countries, heart failure is responsible for 1-2% of all health expenditure, which is mostly driven by repeated hospital admissions. Therefore, there is a considerable need for new therapies to limit the burden of CVD.
This application builds on a ground-breaking discovery by a unique team of clinicians and scientists who provided extensive validation for their findings through a series of basic, pre-clinical and translational research. Our goal is to translate this discovery into benefit for patients. The new therapy is based on selective targeting of a specific immune cell subset, mature B lymphocytes, with the aim to limit deleterious cardiac remodelling and improve heart function recovery post-MI. Of note, the drug that targets this pathway, i.e. CD20 monoclonal antibody (mAb) rituximab, is available for testing in a re-purposing scheme, allowing for rapid initiation of proof-of-concept clinical trials. The PIs of the present proposal have successfully completed a phase 1/2a clinical trial (RITA-MI, NCT03072199), which established the safety of rituximab treatment at the acute phase of MI.
RITA-MI 2 will conduct a phase 2b randomised double-blind placebo-controlled CT to assess the impact of B cell depletion with the CD20 mAb rituximab on left ventricular dysfunction and cardiac remodelling after acute MI.
Ámbito científico
Palabras clave
Programa(s)
Convocatoria de propuestas
Consulte otros proyectos de esta convocatoriaConvocatoria de subcontratación
H2020-SC1-2020-Two-Stage-RTD
Régimen de financiación
RIA - Research and Innovation actionCoordinador
75654 Paris
Francia