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Heart Failure CongestivePhase 2AGENT-HFNCT01966887

AAV1-CMV-Serca2a GENe Therapy Trial in Heart Failure

A Phase 2 study testing MYDICAR-single intracoronary infusion in people with Heart Failure Congestive and Ischemic Cardiomyopathy, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 80 years
What is being tested?
MYDICAR-single intracoronary infusion
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
10 participants
Where
1 siteFrance
Study dates
Dec 2013to Feb 2016
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • <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
Show all 20Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

France1 site

  • CHU Pitié-Salpêtrière

    Paris, 75013

Other trials in France

About this study

Official title: 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.

Read the 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.

Being tested
MYDICAR-single intracoronary infusion, Placebo; single intracoronary infusion
Keywords
Heart failure, Gene therapy, Serca2a, Cardiomyopathy
Medical subject headings
Heart Failure, Cardiomyopathies

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MYDICAR-single intracoronary infusionGenetic

    Also called 1x10e13 DRP; single intracoronary infusion

    AAV1/Serca2a

  • Placebo; single intracoronary infusionGenetic

    single intracoronary infusion

Study groups in NCT01966887
Study groupRoleWhat they receive
MYDICAR-single intracoronary infusionExperimentalGenetic / AAV1 Serca2a (MYDICAR)
Receives: Genetic: MYDICAR-single intracoronary infusion
Placebo; single intracoronary infusionPlacebo comparatorPlacebo comparator
Receives: Genetic: Placebo; single intracoronary infusion

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. left ventricular end-systolic volume measured by CT-Scan

    left ventricular end-systolic volume measured by CT-Scan / changes from baseline to 6 months

    Measured: at 6 months

Secondary outcomes (11)

  1. 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

    Measured: at 6 and 12 months

  2. Cardiac volumes and function

    Cardiac volumes and function / changes from baseline to 6 months \& 12 months

    Measured: at 6 and 12 months

  3. Cardiac hemodynamic parameters

    Cardiac hemodynamic parameters; changes from baseline to 6 months

    Measured: at 6 months

  4. VO2 max

    VO2 max; changes from baseline to 6 months and 12 months

    Measured: at 6 and 12 months

  5. Cardiac function assessed by echocardiography

    Changes from baseline to 6 and12 months in:Echocardiographic assessments

    Measured: at 6 and12 months

  6. Quality of Life (Kansas city score)

    Changes from baseline to 3,6,9,12 months in:Quality of Life

    Measured: at 3,6,9,12 months

  7. NT-ProBNP

    Changes from baseline to 6 and12 months in:NT-ProBNP

    Measured: at 6 and12 months

  8. Time to cardiovascular event

    Time to cardiovascular event (all-cause death, heart transplant, LVAD implantation) - administration to 12 months

    Measured: at 6 and 12 months

  9. Number of hospitalized patients for worsening heart failure

    Measured: at 6 and 12 months

  10. Cardiac volumes assessed by echocardiography

    Changes from baseline to 6 and12 months in:Echocardiographic assessments

    Measured: at 6 and12 months

  11. CT-scan other measurments: left ventricular end-systolic volume

    CT-scan other measurments: left ventricular end-systolic volume / changes from baseline to 12 months

    Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Oct 2013 (estimated)
  2. Study startDec 2013
  3. Primary completionSep 2015
  4. Study completionFeb 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01966887
Sponsor's protocol ID
P081252
Acronym
AGENT-HF
Status last verified
Aug 2017
First submitted
26 Sep 2013
Last updated
29 Aug 2017
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 28393439

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing MYDICAR-single intracoronary infusion in people with Heart Failure Congestive and Ischemic Cardiomyopathy, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 29 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early. Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

left ventricular end-systolic volume measured by CT-Scan (time frame: at 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01966887, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Aug 2017.

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