AAV1-CMV-Serca2a GENe Therapy Trial in Heart Failure

NCT01966887 | Terminated Phase 2 DMC

• 1 other identifier: P081252
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Heart Failure Congestive; Ischemic Cardiomyopathy; Non-ischemic Cardiomyopathy

Keywords

Heart failure; Gene therapy; Serca2a; Cardiomyopathy

Outcome Measures

Primary Outcomes (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

  at 6 months

Secondary Outcomes (11)

• CT-scan other measurments: left ventricular end-diastolic volume

  at 6 and 12 months

• Cardiac volumes and function

  at 6 and 12 months

• Cardiac hemodynamic parameters

  at 6 months

• VO2 max

  at 6 and 12 months

• Cardiac function assessed by echocardiography

  at 6 and12 months

Study Arms (2)

MYDICAR-single intracoronary infusion

EXPERIMENTAL

Genetic / AAV1 Serca2a (MYDICAR)

Genetic: MYDICAR-single intracoronary infusion

Placebo; single intracoronary infusion

PLACEBO COMPARATOR

Placebo comparator

Genetic: Placebo; single intracoronary infusion

Interventions

MYDICAR-single intracoronary infusion GENETIC

AAV1/Serca2a

Also known as: 1x10e13 DRP; single intracoronary infusion

MYDICAR-single intracoronary infusion

Placebo; single intracoronary infusion GENETIC

single intracoronary infusion

Placebo; single intracoronary infusion

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• \<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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Celladon Corporation: collaborator

Study Sites (1)

CHU Pitié-Salpêtrière

Paris, 75013, France

Location

Related Publications (1)

• 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.

  PMID: 28393439 RESULT

MeSH Terms

Conditions

Heart Failure; Cardiomyopathies

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Officials

• Jean-Sébastien HULOT, MDPhD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 26, 2013
• First Posted: October 22, 2013
• Study Start: December 1, 2013
• Primary Completion: September 1, 2015
• Study Completion: February 1, 2016
• Last Updated: August 29, 2017

Record last verified: 2017-08

Locations

FR (1)