AGENT

Étude du transfert du gène Serca2a via un vecteur de type AAV1 (adéno-associated viral 1) pour le traitement de l’insuffisance cardiaque sévère. Étude de Phase 2, en double aveugle, multicentrique, menée sur 44 patients séronégatifs AAV1. 22 patients recevront AAV1-CMV-Serca2a et 22 patients recevront une injection de sérum physiologique, administrés dans les 2 groupes par infusion lente intra-coronaire. Tous les patients seront sous traitement médical optimal. Randomisation stratifiée sur l’étiologie ischémique ou non-ischémique.

The purpose of gene transfer of SERCA2a is to improve systolic and diastolic function of the failing ventricle. Studies show that reduction of SERCA2a in failing ventricle is a key factor in depression of contraction, and that restoration of SERCA2a levels can improve left ventricular function and remodeling.
The aim of the study is to investigate the effect of an adeno-associated viral vector expressing the sarcoplasmic reticulum calcium ATPase (SERCA2a), driven by the CMV promoter (AAV1-CMV-SERCA2a), on the ventricular remodeling of patients with severe heart failure using multimodality cardiac imaging.
This is a Phase 2 monocenter double blind randomized placebo-controled, parallel study. The study will enroll 44 symptomatic heart failure patients with NYHA IIIb/IV, with left-ventricular ejection fraction of 35& or less receiving an optimal standard medical therapy.
The absence of neutralizing antibodies against AAV1 will be primarily checked. Seronegative patients will be randomized to receive either 1x10e13 AAV1-CMV-Serca2a or a placebo as a single intracoronary infusion. Evolution during the next 6 months of the left ventricular end-systolic volume (measured with a 256-slices CT-scan before injection and 6 months later) will be the primary endpoint. Secondary endpoints will include changes in the LVEF, diastolic volumes, VO2max, Echocardiographic remodeling, BNP, cardiac hemodynamics and biological safety profile.

• Effect of intracoronary administration of AAV1/SERCA2a on ventricular remodelling in patients with advanced systolic heart failure : results from the AGENT-HF randomized phase 2 trial
  Jean-Sébastien Hulot, Joe-Elie Salem, Alban Redheuil, Jean-Philippe Collet, Shaida Varnous, Patrick Jourdain, Damien Logeart , Estelle Gandjbakhch, Claude Bernard, Stéphane N Hatem, Richard Isnard, Philippe Cluzel, Claude Le Feuvre, Pascal Leprince, Nadjib Hammoudi, François M Lemoine, David Klatzmann, Eric Vicaut, Michel Komajda, Gilles Montalescot, Anne-Marie Lompré, Roger J Hajjar, AGENT-HF Investigators
  Publié dans European Journal of Heart Failure