A Phase 2b, Double-Blind, Placebo-Controlled, Multinational, Multicenter, Randomized Study Evaluating the Safety and Efficacy of Intracoronary Administration of MYDICAR® (AAV1/SERCA2a) in Subjects with Heart Failure

Phase 1

Conditions: Moderate to advanced heart failure (NYHA class III/IV) due to systolic dysfunction
MedDRA version: 15.0Level: LLTClassification code 10010684Term: Congestive heart failureSystem Organ Class: 10007541 - Cardiac disorders
Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Registration Number: EUCTR2012-001700-37-NL

Lead Sponsor: Celladon Corporation

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 250

Inclusion Criteria

1. Negative neutralizing AAV1 antibodies (NAb) (titer <1:2) within 90 days of screening.
2. 18-80 years of age, inclusive, at the time of signing the informed consent.
3. Chronic systolic HF due to ischemic or dilated cardiomyopathy. Subjects with ischemic cardiomyopathy must have at least one major coronary vessel with TIMI grade 3 flow. If a subject has not undergone coronary angiography within 2 months, this criterion may be assessed after the subject is randomized and undergoes angiography just prior to the planned infusion of investigational product.
4. Left ventricular ejection fraction (LVEF) =35% anytime during the 60-day window prior to administration of investigational product.
5. Diagnosis of NYHA class III/IV HF for a minimum of 90 days prior to screening.
6. Maximal, optimized HF therapy consistent with American College of Cardiology/American Heart Association and European Society of Cardiology practice guidelines for the treatment of chronic heart failure (ACC/AHA/ESC HF guidelines) and as updated from time to time:
a. Medical therapy including oral diuretic, angiotensin-converting enzyme (ACE) inhibitor (or angiotensin-receptor blocker (ARB) if ACE intolerant) and, as tolerated, beta blocker at approved dosages as labeled in the respective package insert. The choice of beta blocker is limited to those approved for heart failure (bisoprolol, carvedilol or sustained release metoprolol succinate). Unless contraindicated or not tolerated, the addition of an aldosterone antagonist should be considered in the absence of hyperkalemia and significant renal dysfunction and according to evolving standards; the final decision is at the discretion of the investigator. Dosing of the above medications must be stable for a minimum of 30 days prior to screening, although up- or down-titration of diuretics, as medically indicated, is permitted. Enrollment of any subject with any deviation from this combination must be preapproved by the medical monitor.
b. Resynchronization therapy, if clinically indicated according to ACC/AHA/ESC HF guidelines, must have been implanted at least 6 months prior to screening.
c. Implantable cardioverter defibrillator (ICD), if clinically indicated according to ACC/AHA/ESC HF guidelines, must have been implanted a minimum of 30 days prior to screening.
d. Cardiac rehabilitation should be consistent with the Agency for Health Care Policy and Research Clinical Practice Guideline, Number 17, Cardiac Rehabilitation. This does not imply that the potential candidate must be enrolled in a cardiac rehabilitation program at screening or in the future.
7. All women of childbearing potential must have a negative urine pregnancy test prior to administration of investigational product and agree to use adequate contraception (defined as oral or injectable contraceptives, intrauterine devices, surgical sterilization or a combination of a condom and spermicide) or limit sexual activity to vasectomized partner for 3 months after administration of investigational product. Men capable of fathering a child must agree to use barrier contraception (combination of a condom and spermicide) or limit activity to post-menopausal, surgically sterilized, or a contraception-practicing partner, for 3 months after administration of investigational product.
8. Ability to sign informed consent form and Release of Medical Information Form.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adult

Exclusion Criteria

1. Any intravenous (IV) therapy with positive inotropes, vasodilators or diuretics within 30 days prior to screening.
2. Restrictive cardiomyopathy, obstructive cardiomyopathy, pericardial disease, amyloidosis, infiltrative cardiomyopathy, uncorrected thyroid disease or discrete LV aneurysm.
3. Cardiac surgery, percutaneous coronary intervention or valvuloplasty within 30 days prior to screening.
4. Myocardial infarction (e.g., ST elevation MI [STEMI] or large non-STEMI) within 90 days prior to screening.
5. Prior heart transplantation, left ventricular reduction surgery (LVRS), cardiomyoplasty, passive restraint device (e.g., CorCap™ Cardiac Support Device), surgically implanted LVAD or cardiac shunt.
6. Likely need for an immediate heart transplant or LVAD implant due to hemodynamic instability.
7. Prior CABG is not considered ideal for inclusion in the study; however, a potential candidate can be reviewed on a case-by-case basis. Ideally, the orifice of the graft should be easy to engage with a catheter and the graft should perfuse a significant amount of potentially viable myocardium.
8. Known hypersensitivity to contrast agents used for angiography; history of, or likely need for, high dose steroid pretreatment prior to contrast angiography.
9. Significant, in the opinion of the investigator, left main or ostial right coronary luminal stenosis.
10. Liver function tests (ALT, AST, alkaline phosphatase) >3x Upper Limit of Normal (ULN) within 30 days prior to investigational product administration or known intrinsic liver disease (e.g., cirrhosis, chronic hepatitis B or hepatitis C virus infection).
11. Current or likely need for hemodialysis within 12 months following enrollment or current GFR =20 mL/minute/1.73 m2 estimated by MDRD calculation.
12. Bleeding diathesis or thrombocytopenia defined as platelet count <50,000 platelets/µL.
13. Anemia defined as hemoglobin <10 g/dL.
14. Known AIDS or HIV seropositive status, or a previous diagnosis of immunodeficiency with an absolute neutrophil count <1000 cells/mm3.
15. Current or history of malugnancy except for basal cell carcinoma.
16. Previous participation in a study of gene transfer; however, if the study was unblinded or documentation otherwise exists that the subject was randomized to the placebo control group and did not receive active gene transfer agent, the subject may be considered for this study.
17. Receiving investigational intervention or participating in another clinical study within 30 days or within 5 half-lives of the investigational drug administration prior to screening. Exception may be made if the individual is enrolled in a non-therapeutic observational study (registry) or the observational portion of a therapeutic study where the sponsoring authority authorizes enrollment.
18. Pregnant or breast-feeding.
19. Recent history of psychiatric disease, including drug or alcohol abuse, that is likely to impair, in the opinion of the investigator, the subject’s ability to comply with protocol-mandated procedures.
20. Other concurrent medical condition(s) that, while not explicitly excluded by the protocol, could jeopardize the safety of the subject or objectives of the study.
Contraindications for Infusion of Investigational Product:
-Suspected or active viral, bacterial, fungal or parasitic infection within 48 hours prior to investigational product administration. If an infection does occur, defer infusion for up to 28 days until resolved.
-Si

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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