Trial record 1 of 4 for: CUPID

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Efficacy and Safety Study of Genetically Targeted Enzyme Replacement Therapy for Advanced Heart Failure (CUPID)

This study is ongoing, but not recruiting participants.

Sponsor:

Information provided by (Responsible Party):

Celladon Corporation

ClinicalTrials.gov Identifier:

NCT00454818

First received: March 30, 2007

Last updated: February 17, 2012

Last verified: February 2012

History of Changes

Tracking Information

First Received Date ^ICMJE

March 30, 2007

Last Updated Date

February 17, 2012

Start Date ^ICMJE

March 2007

Primary Completion Date

August 2010 (final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

Safety and Activity/Efficacy [ Time Frame: 6, 9 and 12 Months ] [ Designated as safety issue: Yes ]

Safety: incidence and severity of AEs, and fatal and non-fatal CV events. Efficacy: peak VO2, 6MWT, echo assessments, NT-proBNP, NYHA Class, MLWHFQ; time to death, LVAD implant or heart transplant and total number of days in hospital.

Original Primary Outcome Measures ^ICMJE

Safety as measured by the incidence and severity of adverse events, all-cause mortality, progression of heart failure leading to hospitalization, and/or IV inotrope, vasodilator, and/or diuretic administration.

Change History

Complete list of historical versions of study NCT00454818 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures ^ICMJE

Additional Safety and Activity/Efficacy [ Time Frame: 6, 9 and 12 Months ] [ Designated as safety issue: Yes ]

Safety: non-CV or unknown fatal events, non-heart-failure-related or non-CV-related hospitalization, and time to first treatment-emergent SAE. Efficacy: BNP, Uric Acid and GDF-15 levels; other echo parameters; rate of hospitalizations per patient-year; days dead, on LVAD, with transplant or in hospital.

Original Secondary Outcome Measures ^ICMJE

Efficacy based on changes from baseline to 3, 6, 9 and 12 months in VO2 max, 6-minute walk test, echocardiographic assessments, NT-proBNP level, NYHA Classification, and Quality of Life assessed by Minnesota Living with Heart Failure Questionnaire.

Current Other Outcome Measures ^ICMJE

Not Provided

Original Other Outcome Measures ^ICMJE

Not Provided

Descriptive Information

Brief Title ^ICMJE

Efficacy and Safety Study of Genetically Targeted Enzyme Replacement Therapy for Advanced Heart Failure

Official Title ^ICMJE

A Phase 1/2 Trial of Intracoronary Administration of MYDICAR® (AAV1/SERCA2a) in Subjects With Heart Failure Divided Into Two Stages: Stage One Open-Label, Sequential Dose-Escalation Cohorts and Stage Two Randomized, Double-Blind, Placebo-Control, Parallel Cohorts

Brief Summary

The study is divided into 2 parts. In the first part, the safety of the gene transfer agent MYDICAR® will be evaluated. In the second part, the ability of MYDICAR® to improve heart function will be studied.

Detailed Description

The American Heart Association (AHA) 2006 update on heart disease reported that 5 million Americans are believed to have symptomatic heart failure (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 will be ~$29.6 billion. Heart failure is a disabling chronic disease and the most frequent discharge diagnosis for hospitalization among older adults. Despite the significant resources expended on the treatment of this disease, outcomes remain poor. The five-year survival for individuals diagnosed with heart failure is less than 50%, and in end-stage heart failure, 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 (LVADs) can be permanently weaned from their device strongly suggests that damaged hearts are capable of recovering lost function.

Clinical studies of MYDICAR® have not yet been conducted in humans. Celladon Corporation (Celladon) proposes to investigate gene transfer as a method to restore SERCA2a function in heart failure (HF) patients using a recombinant adeno-associated viral vector (AAV), which consists of an AAV serotype 1 capsid and contains the human SERCA2a cDNA flanked by Inverted Terminal Repeats (ITR) derived from AAV serotype 2 (AAV1/SERCA2a). MYDICAR® refers to AAV1/SERCA2a drug product intended for administration by percutaneous delivery.

Study Type ^ICMJE

Interventional

Study Phase

Phase 1
Phase 2

Study Design ^ICMJE

Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

Condition ^ICMJE

Heart Failure, Congestive
Dilated Cardiomyopathy

Intervention ^ICMJE

Genetic: MYDICAR®
1.4x10e11 DRP; antegrade epicardial coronary artery infusion

Other Name: AAV1/SERCA2a
Procedure: Placebo Infusion
Saline; epicardial coronary artery infusion
Genetic: MYDICAR®
6x10e11 DRP; antegrade epicardial coronary artery infusion

Other Name: AAV1/SERCA2a
Genetic: MYDICAR®
3x10e12 DRP; antegrade epicardial coronary artery infusion

Other Name: AAV1/SERCA2a
Genetic: MYDICAR®
1x10e13 DRP; antegrade epicardial coronary artery infusion

Other Name: AAV1/SERCA2a

Study Arm (s)

Experimental: MYDICAR Very Low Dose
1.4x10e11 DRP

Intervention: Genetic: MYDICAR®
Experimental: MYDICAR Low Dose
6x10e11 DRP

Intervention: Genetic: MYDICAR®
Experimental: MYDICAR Mid Dose
3x10e12 DRP

Intervention: Genetic: MYDICAR®
Experimental: MYDICAR High Dose
1x10e13 DRP

Intervention: Genetic: MYDICAR®
Placebo Comparator: Placebo
Placebo

Intervention: Procedure: Placebo Infusion

Publications *

Jaski BE, Jessup ML, Mancini DM, Cappola TP, Pauly DF, Greenberg B, Borow K, Dittrich H, Zsebo KM, Hajjar RJ; Calcium Up-Regulation by Percutaneous Administration of Gene Therapy In Cardiac Disease (CUPID) Trial Investigators. Calcium upregulation by percutaneous administration of gene therapy in cardiac disease (CUPID Trial), a first-in-human phase 1/2 clinical trial. J Card Fail. 2009 Apr;15(3):171-81.
Jessup M, Greenberg B, Mancini D, et al. Calcium upregulation by percutaneous administration of gene therapy in cardiac disease (CUPID). A phase 2 trial of intracoronary gene therapy of sarcoplasmic reticulum Ca2+-ATPase in patients with advanced heart failure [published online ahead of print June 27, 2011]. Circulation 2011. doi:10.1161/CIRCULALTIONAHA.111.022889.
Horowitz JD, Rosenson RS, McMurray JJ, Marx N, Remme WJ. Clinical Trials Update AHA Congress 2010. Cardiovasc Drugs Ther. 2011 Feb;25(1):69-76.
Hajjar RJ, Zsebo K, Deckelbaum L, Thompson C, Rudy J, Yaroshinsky A, Ly H, Kawase Y, Wagner K, Borow K, Jaski B, London B, Greenberg B, Pauly DF, Patten R, Starling R, Mancini D, Jessup M. Design of a phase 1/2 trial of intracoronary administration of AAV1/SERCA2a in patients with heart failure. J Card Fail. 2008 Jun;14(5):355-67. Epub 2008 May 27.
Jessup M, Greenberg B, Mancini D, Cappola T, Pauly DF, Jaski B, Yaroshinsky A, Zsebo KM, Dittrich H, Hajjar RJ; Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID) Investigators. Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID): a phase 2 trial of intracoronary gene therapy of sarcoplasmic reticulum Ca2+-ATPase in patients with advanced heart failure. Circulation. 2011 Jul 19;124(3):304-13. Epub 2011 Jun 27.

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Active, not recruiting

Estimated Enrollment ^ICMJE

Estimated Completion Date

August 2012

Primary Completion Date

August 2010 (final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

Inclusion Criteria:

Chronic ischemic or non-ischemic cardiomyopathy. Subjects with ischemic cardiomyopathy must have at least one major coronary vessel with TIMI grade 3 flow.
Left ventricular ejection fraction (LVEF) ≤35%
Diagnosis of NYHA Class III/IV heart failure for a minimum of 3 months prior to screening
Maximal oxygen consumption (VO2 max) ≤20 mL/kg/min within 90 days prior to enrollment
An implantable cardioverter defibrillator (ICD) implanted a minimum of 30 days prior to enrollment
Treatment with appropriate heart failure therapy as tolerated
All women of childbearing potential must have a negative urine pregnancy test prior to administration of investigational product and agree to use adequate contraception. Men capable of fathering a child must agree to use barrier contraception or limit activity to post-menopausal, surgically sterilized, or a contraception-practicing partner, for 3 months after administration of investigational product.
Ability to sign Informed Consent Form (ICF) and Release of Medical Information Form

Exclusion Criteria:

Any intravenous therapy with positive inotropes, vasodilators, or diuretics within 30 days prior to enrollment
Restrictive cardiomyopathy, obstructive cardiomyopathy, pericardial disease, amyloidosis, infiltrative cardiomyopathy, uncorrected thyroid disease, or dyskinetic LV aneurysm
Cardiac surgery, percutaneous coronary intervention, or valvuloplasty within 30 days prior to enrollment
Clinically significant myocardial infarction (e.g., ST elevation MI [STEMI] or large non-STEMI) within 6 months prior to enrollment
Prior heart transplantation, left ventricular reduction surgery (LVRS), cardiomyoplasty, passive restraint device (e.g., CorCap™ Cardiac Support Device), surgically implanted LVAD or cardiac shunt
Likely to receive cardiac resynchronization therapy, cardiomyoplasty, LVRS, heart transplant, conventional revascularization procedure, or valvular repair within 6 months following enrollment
Patients with prior coronary artery bypass graft(s) (CABG) will reviewed on a case-by-case basis
No evidence of functional or viable myocardium
Exercise capacity primarily limited by obesity, peripheral vascular disease, intrinsic pulmonary disease or orthopedic problems and not by underlying heart failure
Known hypersensitivity to octafluoropropane (component of the intravenous echocardiography contrast agent, DEFINITY®) or other contrast dyes used for angiography; history of, or likely need for, high dose steroid pretreatment prior to contrast angiography
A left ventricle that is difficult to image or high quality echocardiography is not obtainable at screening
Significant left main or ostial right coronary lumenal stenosis in the opinion of the investigator
Expected survival <1 year in the investigator's medical opinion
Suspected or active viral, bacterial, fungal, or parasitic infection within 48 hours prior to enrollment
Liver function tests (ALT, AST, alkaline phosphatase) >2x Upper Limit of Normal (ULN) within 30 days prior to enrollment or known intrinsic liver disease (e.g., cirrhosis, chronic hepatitis B or hepatitis C virus infection)
Current or likely need for hemodialysis within 12 months following enrollment
Bleeding diathesis or thrombocytopenia defined as platelet count <50,000 platelets/μL
Anemia defined as hemoglobin <10 g/dL
Known AIDS or HIV-positive status, or a previous diagnosis of immunodeficiency with an absolute neutrophil count <1000 cells/mm3
Previous participation in a study of gene transfer
Presence of neutralizing anti-AAV1 antibodies at titer ≥1:2 within 3 months of screening
Receiving investigational intervention or participating in another clinical study within 30 days or within 5 half-lives of the investigational drug administration prior to enrollment
Pregnancy or lactation
Recent history of psychiatric disease (including drug or alcohol abuse) that is likely to impair subject's ability to comply with protocol-mandated procedures, in the opinion of the investigator
Other concurrent medical condition(s) that, while not explicitly excluded by the protocol, could jeopardize the safety of the patient or objectives of the study

Gender

Both

Ages

18 Years to 75 Years

Accepts Healthy Volunteers

Contacts ^ICMJE

Contact information is only displayed when the study is recruiting subjects

Location Countries ^ICMJE

United States

Administrative Information

NCT Number ^ICMJE

NCT00454818

Other Study ID Numbers ^ICMJE

CELL-001, CUPID Trial

Has Data Monitoring Committee

Yes

Responsible Party

Celladon Corporation

Study Sponsor ^ICMJE

Celladon Corporation

Collaborators ^ICMJE

Not Provided

Investigators ^ICMJE

Principal Investigator:	Brian Jaski, MD	San Diego Cardiac Center
Principal Investigator:	Donna Mancini, MD	Columbia University Hospital
Principal Investigator:	Randall Starling, MD	The Cleveland Clinic
Study Chair:	Mariell Jessup, MD	University of Pennsylvania
Principal Investigator:	Thomas Cappola, MD, ScM	University of Pennsylvania
Principal Investigator:	Daniel Pauly, MD	Shands Hospital, University of Florida at Gainesville
Principal Investigator:	Barry London, MD	University of Pittsburgh
Principal Investigator:	Barry Greenberg, MD	University of California at San Diego Medical Center
Principal Investigator:	A. G. Kfoury, MD	Intermountain Medical Center
Principal Investigator:	Stephen Archer, MD	University of Chicago
Principal Investigator:	Andrew Kao, MD	Mid America Heart Institute, Saint Luke's Hospital
Principal Investigator:	Paul J. Hauptman, MD	St. Louis University Hospital
Principal Investigator:	Jill Kalman, MD	Mount Sinai School of Medicine
Principal Investigator:	Douglas W. Losordo, MD	Northwestern University
Principal Investigator:	Eric J. Eichhorn, MD, FACC	Cardiopulmonary Research Science and Technology Institutte, Medical City Dallas Hospital
Principal Investigator:	Stephanie H. Dunlap, DO	University of Cincinnati
Principal Investigator:	Vinay Thohan, MD	Wake Forest University
Principal Investigator:	Maryl R. Johnson, MD	University of Wisconsin, Madison
Principal Investigator:	Mark Dunlap, MD	MetroHealth Medical Center
Principal Investigator:	Joaquin E. Cigarroa, MD	Oregon Health and Science University
Principal Investigator:	Dinesh K. Gupta, MD	Tennessee Center for Clinical Trials, Harton Regional Medical Center
Principal Investigator:	Marc Klapholz, MD	University of Medicine and Dentistry New Jersey
Principal Investigator:	Guillermo Torre, MD	The Methodist Hospital System

Information Provided By

Celladon Corporation

Verification Date

February 2012

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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