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AAV1-CMV-Serca2a GENe Therapy Trial in Heart Failure (AGENT-HF)

This study has been terminated.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01966887
First Posted: October 22, 2013
Last Update Posted: August 29, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Celladon Corporation
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
  Purpose
The purpose of this study is to determine the effect of intracoronary SERCA2a Gene transfer on cardiac volumes and function using multimodality cardiac imaging.

Condition Intervention Phase
Heart Failure Congestive Ischemic Cardiomyopathy Non-ischemic Cardiomyopathy Genetic: MYDICAR-single intracoronary infusion Genetic: Placebo; single intracoronary infusion Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Phase 2 Study of SERCA2a Gene Transfer in Patients With Severe Heart Failure

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • left ventricular end-systolic volume measured by CT-Scan [ Time Frame: at 6 months ]
    left ventricular end-systolic volume measured by CT-Scan / changes from baseline to 6 months


Secondary Outcome Measures:
  • CT-scan other measurments: left ventricular end-diastolic volume [ Time Frame: at 6 and 12 months ]
    CT-scan other measurments: left ventricular end-diastolic volume / changes from baseline to 6 and 12 months

  • Cardiac volumes and function [ Time Frame: at 6 and 12 months ]
    Cardiac volumes and function / changes from baseline to 6 months & 12 months

  • Cardiac hemodynamic parameters [ Time Frame: at 6 months ]
    Cardiac hemodynamic parameters; changes from baseline to 6 months

  • VO2 max [ Time Frame: at 6 and 12 months ]
    VO2 max; changes from baseline to 6 months and 12 months

  • Cardiac function assessed by echocardiography [ Time Frame: at 6 and12 months ]
    Changes from baseline to 6 and12 months in:Echocardiographic assessments

  • Quality of Life (Kansas city score) [ Time Frame: at 3,6,9,12 months ]
    Changes from baseline to 3,6,9,12 months in:Quality of Life

  • NT-ProBNP [ Time Frame: at 6 and12 months ]
    Changes from baseline to 6 and12 months in:NT-ProBNP

  • Time to cardiovascular event [ Time Frame: at 6 and 12 months ]
    Time to cardiovascular event (all-cause death, heart transplant, LVAD implantation) - administration to 12 months

  • Number of hospitalized patients for worsening heart failure [ Time Frame: at 6 and 12 months ]
  • Cardiac volumes assessed by echocardiography [ Time Frame: at 6 and12 months ]
    Changes from baseline to 6 and12 months in:Echocardiographic assessments

  • CT-scan other measurments: left ventricular end-systolic volume [ Time Frame: 12 months ]
    CT-scan other measurments: left ventricular end-systolic volume / changes from baseline to 12 months


Enrollment: 10
Study Start Date: December 2013
Study Completion Date: February 2016
Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MYDICAR-single intracoronary infusion
Genetic / AAV1 Serca2a (MYDICAR)
Genetic: MYDICAR-single intracoronary infusion
AAV1/Serca2a
Other Name: 1x10e13 DRP; single intracoronary infusion
Placebo Comparator: Placebo; single intracoronary infusion
Placebo comparator
Genetic: Placebo; single intracoronary infusion
single intracoronary infusion

Detailed Description:
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.
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with NYHA class III / IV severe heart failure ≥ 3 months
  • Ischemic or non-ischemic origin
  • Left ventricular ejection fraction ≤35%
  • Patients must be receiving optimal (maximum tolerated doses) medical treatment (diuretics, renin-angiotensin-aldosterone system blockers, beta blockers, ±Ivabradine) for at least 1 month (with the exception of diuretic dose titration) and must be stable.
  • No decompensated congestive heart failure within the past month
  • With or without an ICD if the ICD was implanted over 3 months ago, with or without biventricular pacing if the RCT was implanted over 6 months ago
  • All women of childbearing potential must have a negative urine pregnancy test prior to administration of investigational medicinal product
  • Patient must have given written informed consent to participate in this study

Exclusion Criteria:

  • <18 or >80 years old
  • AAV1 seropositivity (titer <1:2) in the last 3 months
  • Atrial fibrillation in the absence of permanent ventricular pacing
  • Coronary revascularization or heart surgery or pacemaker implantation < 3 months
  • Ischemic heart disease without at least one coronary artery with a TIMI-3 flow
  • Restrictive cardiomyopathy, hypertrophic obstructive cardiomyopathy, pericardial disease, cardiac amyloidosis
  • Heart transplant, an already implanted or needing to urgently implant external ventricular assist device
  • Myocardial infarction (STEMI or NSTEMI) < 3 months
  • Treatment with intravenous positive inotropic agents or diuretics in the past 28 days
  • Pregnant or nursing patient
  • Female patient of childbearing age with no effective means of contraception
  • Severe renal failure defined by a creatinine clearance of < 30 mL/min (last bloodwork done less than 6 months)
  • Liver failure, chronic liver disease or laboratory tests > 3 x N (AST, ALT, ALP))(last bloodwork done less than 6 months)
  • Thrombocytopenia (<50,000/mm3
  • Patient treated with immunosuppressants, has an immunodeficiency or whose neutrophil count < 1000 mm3
  • Recent sepsis (< 3 months)
  • Active neoplasia or treated < 5 years
  • No medical insurance
  • Patient is enrolled in another randomized study
  • Patient does not understand the protocol procedures sponsor suspects poor compliance with the protocol
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01966887


Locations
France
CHU Pitié-Salpêtrière
Paris, France, 75013
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Celladon Corporation
Investigators
Principal Investigator: Jean-Sébastien HULOT, MDPhD Assistance Publique - Hôpitaux de Paris
  More Information

Publications:
Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01966887     History of Changes
Other Study ID Numbers: P081252
First Submitted: September 26, 2013
First Posted: October 22, 2013
Last Update Posted: August 29, 2017
Last Verified: August 2017

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Heart failure
Gene therapy
Serca2a
Cardiomyopathy

Additional relevant MeSH terms:
Heart Failure
Cardiomyopathies
Heart Diseases
Cardiovascular Diseases