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A Phase 1/2 Study of High-dose Genetically Targeted Enzyme Replacement Therapy for Advanced Heart Failure | Clinical Trials | Clareo Health

TERMINATEDPHASE1/PHASE2

A Phase 1/2 Study of High-dose Genetically Targeted Enzyme Replacement Therapy for Advanced Heart Failure

A Phase 1/2 Study of the Safety and Preliminary Activity of MYDICAR® at a Dose of 2.5 x 10^13 DNase Resistant Particles (DRP) in Subjects With Advanced Heart Failure Divided Into 2 Phases: Phase 1 Open-label and Phase 2 Randomized, Double-blind, Placebo-controlled

NCT02346422•Celladon Corporation

View on ClinicalTrials.gov

Summary

The purpose of this trial is to characterize the safety profile and preliminary activity of high-dose MYDICAR® in persons with advanced heart failure when added to their maximal and optimized therapy.

Detailed Description

Heart failure (HF) is a disabling chronic disease and the most frequent discharge diagnosis for hospitalization among older adults.The American Heart Association (AHA) 2006 update on heart disease reported that 5 million Americans are believed to have symptomatic HF, and 550,000 patients are newly diagnosed each year. The estimated direct and indirect cost of HF in the United States (U.S.) for 2006 was \~$29.6 billion. Despite the significant resources expended on the treatment of this disease, outcomes remain poor. The five-year survival for individuals diagnosed with HF is less than 50%, and in end-stage HF, the one-year survival may be as low as 25% regardless of medical therapy. Recent studies suggest that the failing heart is not refractory to treatment, as was previously believed. For example, the observation that a small percentage of subjects with left ventricular assist devices can be permanently weaned from their device strongly suggests that damaged hearts are capable of recovering lost function. Celladon Corporation (Celladon) is investigating gene transfer as a method to restore calcium ion (Ca++) cycling in HF patients. The gene therapy vehicle uses a recombinant adeno-associated viral vector (AAV), which consists of an AAV serotype 1 capsid and contains the human sarcoplasmic reticulum Ca++ ATPAse (SERCA2a) complementary DNA (cDNA) flanked by inverted terminal repeats derived from AAV serotype 2 (AAV1/SERCA2a). MYDICAR® refers to AAV1/SERCA2a drug product intended for administration by percutaneous delivery. Phase 1/2 clinical trials have demonstrated initial safety and evidence of improvement in clinical outcomes at MYDICAR doses of up to 1 x 10\^13 DNase-resistant particles (DRP). The trial described here is designed to investigate the safety profile and preliminary activity of MYDICAR at a dose of 2.5 x 10\^13 DRP; this dose is 2.5-fold higher than previously investigated doses.

Eligibility

Age

18 - 80 years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Unless otherwise specified, screening must be performed within 30 days prior to enrollment (phase 1) or enrollment/randomization (phase 2) except as noted below. Subjects must meet the following criteria to be eligible for the study:
•1. AAV1 neutralizing antibodies (NAb) negative (titer \<1:2 or equivocal) within 60 days prior to screening.
•2. Age 18-80 years, inclusive, at the time of signing the first informed consent.
•3. Chronic ischemic or non-ischemic cardiomyopathy, except for hypertrophic cardiomyopathy. Toxic or alcoholic cardiomyopathies are allowed as long as toxin or alcohol exposure has been eliminated and a sufficient amount of time has elapsed to rule out spontaneous recovery. Similarly, patients with viral or peripartum cardiomyopathy will not be enrolled until sufficient time has elapsed to rule out spontaneous recovery. Subjects with ischemic cardiomyopathy must have at least 1 major coronary vessel with thrombolysis in myocardial infarction (TIMI) grade 3 flow. (If a subject has not undergone recent coronary angiography, TIMI flow may be assessed during the study angiography just prior to investigational medicinal product \[IMP\] infusion).
•4. Left ventricular ejection fraction ≤35%.
•5. Diagnosis of New York Heart Association class III/IV heart failure (HF) for a minimum of 60 days prior to screening.
•6. For phase 2 only, the presence of at least one of the following risk factors:
•1. Hospitalization for HF within 6 months of screening, or in lieu of hospitalization, at least 2 outpatient interventions for the intended treatment of signs and symptoms of worsening HF (e.g., intravenous \[IV\] diuretics, peripheral ultrafiltration).
•2. N-terminal prohormone brain natriuretic peptide (NT-proBNP) \>1200 pg/mL within 30 days of screening; if subject is in atrial fibrillation, NT-proBNP \>1600 pg/mL within 30 days of screening.
•7. Individualized, maximal, optimized HF therapy consistent with American College of Cardiology/American Heart Association practice guidelines for the treatment of chronic heart failure (ACC/AHA HF guidelines) and as updated from time to time:
+14 more criteria

Exclusion Criteria

•Subjects meeting any of the following criteria will be excluded from the study:
•1. De novo diagnosis of heart failure.
•2. Any IV therapy with positive inotropes, vasodilators or diuretics within 30 days prior to screening or enrollment.
•3. Restrictive cardiomyopathy, obstructive cardiomyopathy, acute myocarditis, pericardial disease, amyloidosis, infiltrative cardiomyopathy, uncorrected thyroid disease or discrete left ventricular aneurysm.
•4. Cardiac surgery, percutaneous coronary intervention, valvuloplasty or valve replacement within 30 days prior to screening.
•5. Myocardial infarction (e.g., ST elevation myocardial infarction \[STEMI\] or large non-STEMI) within 90 days prior to screening. Large non-STEMI shall be defined \>3x the upper limit of normal (ULN) for creatinine kinase test or \>5x ULN for troponin.
•6. Prior heart transplantation, left ventricular reduction surgery (LVRS), cardiomyoplasty, passive restraint device (e.g., CorCap™ Cardiac Support Device), mechanical circulatory support device (MCSD) or cardiac shunt.
•7. Likely to receive cardiac resynchronization therapy, cardiomyoplasty, LVRS, conventional revascularization procedure or valvular repair in the 6 months following treatment.
•8. Likely need for an immediate heart transplant or MCSD implant due to hemodynamic instability.
•9. Prior coronary artery bypass graft(s) is not necessarily exclusionary. A potential candidate should be reviewed on a case-by-case basis by the treating interventionist, taking into account the dominance of the system, the accessibility of the graft(s) orifice, and the contribution of the graft vessel(s) and native coronary arteries to viable myocardial perfusion. The case and tentative infusion strategy must be discussed with the medical or safety officer prior to enrollment of the subject into the study.
+12 more criteria

Locations (4)

La Jolla, California, United States

San Diego, California, United States

Kansas City, Missouri, United States

New York, New York, United States

Key Dates

Start Date

April 1, 2015

Primary Completion Date

June 26, 2015

Last Updated

January 31, 2017

Enrollment

ACTUAL participants

Conditions

Ischemic CardiomyopathyNon-ischemic CardiomyopathyHeart FailureCardiomyopathies

Interventions

MYDICAR Phase 1

GENETIC

MYDICAR Phase 2

GENETIC

Placebo Phase 2 only

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: January 31, 2017Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

A Phase 1/2 Study of High-dose Genetically Targeted Enzyme Replacement Therapy for Advanced Heart Failure

Inclusion Criteria

Exclusion Criteria

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