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

August 28, 2017 updated by: Assistance Publique - Hôpitaux de Paris

Phase 2 Study of SERCA2a Gene Transfer in Patients With Severe Heart Failure

The purpose of this study is to determine the effect of intracoronary SERCA2a Gene transfer on cardiac volumes and function using multimodality cardiac imaging.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
10

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Paris, France, 75013
        • CHU Pitié-Salpétrière

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: MYDICAR-single intracoronary infusion
Genetic / AAV1 Serca2a (MYDICAR)
Genetic: MYDICAR-single intracoronary infusion
AAV1/Serca2a
Other Names:
  • 1x10e13 DRP; single intracoronary infusion
PLACEBO_COMPARATOR: Placebo; single intracoronary infusion
Placebo comparator
Genetic: Placebo; single intracoronary infusion
single intracoronary infusion

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
at 6 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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
at 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
at 6 and 12 months
Cardiac hemodynamic parameters
Time Frame: at 6 months
Cardiac hemodynamic parameters; changes from baseline to 6 months
at 6 months
VO2 max
Time Frame: at 6 and 12 months
VO2 max; changes from baseline to 6 months and 12 months
at 6 and 12 months
Cardiac function assessed by echocardiography
Time Frame: at 6 and12 months
Changes from baseline to 6 and12 months in:Echocardiographic assessments
at 6 and12 months
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
at 3,6,9,12 months
NT-ProBNP
Time Frame: at 6 and12 months
Changes from baseline to 6 and12 months in:NT-ProBNP
at 6 and12 months
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
at 6 and 12 months
Number of hospitalized patients for worsening heart failure
Time Frame: at 6 and 12 months
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
at 6 and12 months
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
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Assistance Publique - Hôpitaux de Paris

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Celladon Corporation

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Jean-Sébastien HULOT, MDPhD, Assistance Publique - Hôpitaux de Paris

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2013

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2015

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 1, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 26, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 17, 2013

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 22, 2013

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 29, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 28, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • P081252

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings