Journal article
Design of a Phase 1/2 Trial of Intracoronary Administration of AAV1/SERCA2a in Patients With Heart Failure
Journal of cardiac failure, Vol.14(5), pp.355-367
2008
DOI: 10.1016/j.cardfail.2008.02.005
PMID: 18514926
Abstract
Heart failure (HF) remains a major cause of morbidity and mortality in North America. With an aging population and an unmet clinical need by current pharmacologic and device-related therapeutic strategies, novel treatment options for HF are being explored. One such promising strategy is gene therapy to target underlying molecular anomalies in the dysfunctional cardiomyocyte. Prior animal and human studies have documented decreased expression of SERCA2a, a major cardiac calcium cycling protein, as a major defect found in HF.
We hypothesize that increasing the activity of SERCA2a in patients with moderate to severe HF will improve their cardiac function, disease status, and quality of life. Gene transfer of SERCA2a will be performed via an adeno-associated viral (AAV) vector, derived from a nonpathogenic virus with long-term transgene expression as well as a clinically established favorable safety profile.
We describe the design of a phase 1 clinical trial of antegrade epicardial coronary artery infusion (AECAI) administration of AAVI/SERCA2a (MYDICAR) to subjects with HF divided into 2 stages: in Stage 1, subjects will be assigned open-label MYDICAR in one of up to 4 sequential dose escalation cohorts; in Stage 2, subjects will be randomized in parallel to 2 or 3 doses of MYDICAR or placebo in a double-blinded manner.
Details
- Title: Subtitle
- Design of a Phase 1/2 Trial of Intracoronary Administration of AAV1/SERCA2a in Patients With Heart Failure
- Creators
- Roger J Hajjar - Mount Sinai School of Medicine, New York, New YorkKrisztina Zsebo - Celladon Corporation, San Diego, CaliforniaLawrence Deckelbaum - Johnson & Johnson Pharmaceutical Research & Development, LLC, Radnor, PACraig Thompson - Division of Cardiology, Dartmouth College, Hanover, New HampshireJeff Rudy - Celladon Corporation, San Diego, CaliforniaAlex Yaroshinsky - Celladon Corporation, San Diego, CaliforniaHung Ly - Mount Sinai School of Medicine, New York, New YorkYoshiaki Kawase - Mount Sinai School of Medicine, New York, New YorkKim Wagner - Celladon Corporation, San Diego, CaliforniaKenneth Borow - Encorium Group, Inc., Wayne, PennsylvaniaBrian Jaski - San Diego Cardiac Center/Sharp Hospital, San Diego, CaliforniaBarry London - University of Pittsburgh Medical Center, Pittsburgh, PennsylvaniaBarry Greenberg - University of California at San Diego Medical Center, San Diego, CaliforniaDaniel F Pauly - Shands Hospital, University of Florida, Gainesville, FloridaRichard Patten - New England Medical Center, Tufts University, Boston, MassachusettsRandall Starling - Cleveland Clinic, Cleveland, OhioDonna Mancini - Columbia University Hospital, New York, New YorkMariell Jessup - Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
- Resource Type
- Journal article
- Publication Details
- Journal of cardiac failure, Vol.14(5), pp.355-367
- DOI
- 10.1016/j.cardfail.2008.02.005
- PMID
- 18514926
- NLM abbreviation
- J Card Fail
- ISSN
- 1071-9164
- eISSN
- 1532-8414
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 2008
- Academic Unit
- Molecular Physiology and Biophysics; Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984025323902771
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