Back to resultsAAV1-CMV-Serca2a GENe Therapy Trial in Heart Failure (AGENT-HF)
Primary Purpose
Heart Failure Congestive, Ischemic Cardiomyopathy, Non-ischemic Cardiomyopathy
Status
Terminated
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
MYDICAR-single intracoronary infusion
Placebo; single intracoronary infusion
Sponsored by
About this trial
This is an interventional treatment trial for Heart Failure Congestive focused on measuring Heart failure, Gene therapy, Serca2a, Cardiomyopathy
Eligibility 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
Sites / Locations
- CHU Pitié-Salpêtrière
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
MYDICAR-single intracoronary infusion
Placebo; single intracoronary infusion
Arm Description
Genetic / AAV1 Serca2a (MYDICAR)
Placebo comparator
Outcomes
Primary Outcome Measures
left ventricular end-systolic volume measured by CT-Scan
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
CT-scan other measurments: left ventricular end-diastolic volume / changes from baseline to 6 and 12 months
Cardiac volumes and function
Cardiac volumes and function / changes from baseline to 6 months & 12 months
Cardiac hemodynamic parameters
Cardiac hemodynamic parameters; changes from baseline to 6 months
VO2 max
VO2 max; changes from baseline to 6 months and 12 months
Cardiac function assessed by echocardiography
Changes from baseline to 6 and12 months in:Echocardiographic assessments
Quality of Life (Kansas city score)
Changes from baseline to 3,6,9,12 months in:Quality of Life
NT-ProBNP
Changes from baseline to 6 and12 months in:NT-ProBNP
Time to cardiovascular event
Time to cardiovascular event (all-cause death, heart transplant, LVAD implantation) - administration to 12 months
Number of hospitalized patients for worsening heart failure
Cardiac volumes assessed by echocardiography
Changes from baseline to 6 and12 months in:Echocardiographic assessments
CT-scan other measurments: left ventricular end-systolic volume
CT-scan other measurments: left ventricular end-systolic volume / changes from baseline to 12 months
Full Information
NCT ID
NCT01966887
First Posted
September 26, 2013
Last Updated
August 28, 2017
Sponsor
Assistance Publique - Hôpitaux de Paris
Collaborators
Celladon Corporation
1. Study Identification
Unique Protocol Identification Number
NCT01966887
Brief Title
AAV1-CMV-Serca2a GENe Therapy Trial in Heart Failure
Acronym
AGENT-HF
Official Title
Phase 2 Study of SERCA2a Gene Transfer in Patients With Severe Heart Failure
Study Type
Interventional
2. Study Status
Record Verification Date
August 2017
Overall Recruitment Status
Terminated
Study Start Date
December 2013 (undefined)
Primary Completion Date
September 2015 (Actual)
Study Completion Date
February 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris
Collaborators
Celladon Corporation
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to determine the effect of intracoronary SERCA2a Gene transfer on cardiac volumes and function using multimodality cardiac imaging.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure Congestive, Ischemic Cardiomyopathy, Non-ischemic Cardiomyopathy
Keywords
Heart failure, Gene therapy, Serca2a, Cardiomyopathy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
10 (Actual)
8. Arms, Groups, and Interventions
Arm Title
MYDICAR-single intracoronary infusion
Arm Type
Experimental
Arm Description
Genetic / AAV1 Serca2a (MYDICAR)
Arm Title
Placebo; single intracoronary infusion
Arm Type
Placebo Comparator
Arm Description
Placebo comparator
Intervention Type
Genetic
Intervention Name(s)
MYDICAR-single intracoronary infusion
Other Intervention Name(s)
1x10e13 DRP; single intracoronary infusion
Intervention Description
AAV1/Serca2a
Intervention Type
Genetic
Intervention Name(s)
Placebo; single intracoronary infusion
Intervention Description
single intracoronary infusion
Primary Outcome Measure Information:
Title
left ventricular end-systolic volume measured by CT-Scan
Description
left ventricular end-systolic volume measured by CT-Scan / changes from baseline to 6 months
Time Frame
at 6 months
Secondary Outcome Measure Information:
Title
CT-scan other measurments: left ventricular end-diastolic volume
Description
CT-scan other measurments: left ventricular end-diastolic volume / changes from baseline to 6 and 12 months
Time Frame
at 6 and 12 months
Title
Cardiac volumes and function
Description
Cardiac volumes and function / changes from baseline to 6 months & 12 months
Time Frame
at 6 and 12 months
Title
Cardiac hemodynamic parameters
Description
Cardiac hemodynamic parameters; changes from baseline to 6 months
Time Frame
at 6 months
Title
VO2 max
Description
VO2 max; changes from baseline to 6 months and 12 months
Time Frame
at 6 and 12 months
Title
Cardiac function assessed by echocardiography
Description
Changes from baseline to 6 and12 months in:Echocardiographic assessments
Time Frame
at 6 and12 months
Title
Quality of Life (Kansas city score)
Description
Changes from baseline to 3,6,9,12 months in:Quality of Life
Time Frame
at 3,6,9,12 months
Title
NT-ProBNP
Description
Changes from baseline to 6 and12 months in:NT-ProBNP
Time Frame
at 6 and12 months
Title
Time to cardiovascular event
Description
Time to cardiovascular event (all-cause death, heart transplant, LVAD implantation) - administration to 12 months
Time Frame
at 6 and 12 months
Title
Number of hospitalized patients for worsening heart failure
Time Frame
at 6 and 12 months
Title
Cardiac volumes assessed by echocardiography
Description
Changes from baseline to 6 and12 months in:Echocardiographic assessments
Time Frame
at 6 and12 months
Title
CT-scan other measurments: left ventricular end-systolic volume
Description
CT-scan other measurments: left ventricular end-systolic volume / changes from baseline to 12 months
Time Frame
12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jean-Sébastien HULOT, MDPhD
Organizational Affiliation
Assistance Publique - Hôpitaux de Paris
Official's Role
Principal Investigator
Facility Information:
Facility Name
CHU Pitié-Salpêtrière
City
Paris
ZIP/Postal Code
75013
Country
France
12. IPD Sharing Statement
Citations:
PubMed Identifier
28393439
Citation
Hulot JS, Salem JE, Redheuil A, Collet JP, Varnous S, Jourdain P, Logeart D, Gandjbakhch E, Bernard C, Hatem SN, Isnard R, Cluzel P, Le Feuvre C, Leprince P, Hammoudi N, Lemoine FM, Klatzmann D, Vicaut E, Komajda M, Montalescot G, Lompre AM, Hajjar RJ; AGENT-HF Investigators. 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. Eur J Heart Fail. 2017 Nov;19(11):1534-1541. doi: 10.1002/ejhf.826. Epub 2017 Apr 10.
Results Reference
result
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AAV1-CMV-Serca2a GENe Therapy Trial in Heart Failure
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