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Rituximab in patients with acute myocardial infarction: a phase 2 placebo-controlled randomised clinical trial

Project description

Repurposing a leukaemia drug against heart failure

Acute myocardial infarction (MI) causes left ventricular dysfunction and heart failure in nearly 50 % of patients. Following extensive preclinical testing, the EU-funded RITA-MI 2 project aims to repurpose an existing drug, rituximab, currently employed for lymphoid malignancies and autoimmune disorders such as rheumatoid arthritis. Rituximab is a monoclonal antibody that selectively targets mature B lymphocytes expressing CD20. The rationale is to stop or limit the deleterious cardiac remodelling that takes place after MI and improve heart function recovery. RITA-MI 2 will assess the impact of B lymphocyte depletion in patients with MI in a phase 2b clinical trial.

Objective

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.

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RIA - Research and Innovation action

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Call for proposal

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(opens in new window) H2020-SC1-BHC-2018-2020

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Coordinator

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 258 750,00
Address
RUE DE TOLBIAC 101
75654 Paris
France

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Region
Ile-de-France Ile-de-France Paris
Activity type
Research Organisations
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 258 750,00

Participants (13)

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