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Ischemic CardiomyopathyPhase 2CUPID-2bNCT01643330

A Study of Genetically Targeted Enzyme Replacement Therapy for Advanced Heart Failure

A Phase 2 study testing AAV1/SERCA2a (MYDICAR) in people with Ischemic Cardiomyopathy and Non-ischemic Cardiomyopathy, run by Celladon Corporation at 54 sites in 10 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The purpose of this trial is to assess whether MYDICAR can reduce the frequency and/or delay heart failure related hospitalizations in persons with advanced heart failure when added to their maximal and optimized therapy. Read more about this study

Who is it for?
Ages 18 to 80 years
What is being tested?
AAV1/SERCA2a (MYDICAR)
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
250 participants
Where
54 sitesin 10 countries
Study dates
Jul 2012to Feb 2016
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Unless otherwise specified, screening must be performed within 30 days prior to administration of investigational medicinal product on Day 0 except as noted under Inclusion Criteria #1 and 4. Subjects must meet the following criteria to be eligible for the study:
  • Negative neutralizing AAV1 antibodies (NAb) (titer <1:2 or equivocal) within 90 days of screening.
  • 18-80 years of age, inclusive, at the time of signing the informed consent.
  • Chronic systolic HF due to ischemic or non-ischemic cardiomyopathy. Subjects with ischemic cardiomyopathy must have at least one major coronary vessel with Thrombolysis in Myocardial Infarction (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 medicinal product.
  • Hypertrophic cardiomyopathy is excluded.
  • Toxic and alcoholic cardiomyopathies are allowed as long as toxin or alcohol exposure has been eliminated and a sufficient amount of limit has elapsed to rule-out spontaneous recovery.
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  • Left ventricular ejection fraction (LVEF) ≤35% anytime during the 60-day window prior to administration of investigational medicinal product.
  • Diagnosis of New York Heart Association (NYHA) class II, III or IV HF for a minimum of 90 days prior to screening.
  • Individualized, maximal, optimized HF therapy consistent with American College of Cardiology (ACC)/American Heart Association (AHA) and European Society of Cardiology (ESC) practice guidelines for the treatment of chronic heart failure (ACC/AHA/ESC HF guidelines) and as updated from time to time:
  • Medical therapy as appropriate to the individual subject 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 in all participating countries (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.
  • Resynchronization therapy, if clinically indicated according to ACC/AHA/ESC HF guidelines, must have been implanted at least 6 months prior to screening.
  • 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.
  • 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.
  • All women of childbearing potential must have a negative urine pregnancy test prior to administration of investigational medicinal 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 medicinal 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 medicinal product.
  • Ability to understand and comply with study requirements as evidenced by providing signed written informed consent form and Release of Medical Information Form.
  • Presence of at least one of the following risk factors:
  • Hospitalization for heart failure 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 heart failure (e.g., intravenous diuretics, peripheral ultrafiltration)
  • N-terminal pro-B-type natriuretic peptide (NT-proBNP) >1200 pg/mL (BNP >225 pg/mL) within 30 days of screening; if subject is in atrial fibrillation, NT-proBNP >1600 pg/mL (BNP >275 pg/mL) within 30 days of screening
  • In Germany only: Medically indicated for diagnostic angiography at the clinician's discretion.

Who cannot join

  • Subjects meeting any of the following criteria will be excluded from the study:
  • Any intravenous (IV) therapy with positive inotropes, vasodilators or diuretics within 30 days prior to screening.
  • Restrictive cardiomyopathy, obstructive cardiomyopathy, acute myocarditis, pericardial disease, amyloidosis, infiltrative cardiomyopathy, uncorrected thyroid disease or discrete LV aneurysm.
  • Cardiac surgery, percutaneous coronary intervention (PCI) or valvuloplasty within 30 days prior to screening.
  • Myocardial infarction (MI) (e.g., ST elevation MI [STEMI] or large non-STEMI) within 90 days prior to screening. Large non-STEMI shall be defined >3x upper limit of normal (ULN) for creatinine kinase (CK)-MB or >5x ULN for troponin.
  • Prior heart transplantation, left ventricular reduction surgery (LVRS), cardiomyoplasty, passive restraint device (e.g., CorCap™ Cardiac Support Device), surgically implanted left ventricular assist device (LVAD) or cardiac shunt.
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  • Likely need for an immediate heart transplant or LVAD implant due to hemodynamic instability.
  • Prior coronary artery bypass grafting (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.
  • Known hypersensitivity to contrast agents used for angiography; history of, or likely need for, high dose steroid pretreatment prior to contrast angiography.
  • Significant, in the opinion of the investigator, left main or ostial right coronary luminal stenosis.
  • Liver function tests (alanine amino transferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase) >3x ULN within 30 days prior to investigational medicinal product administration 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 or current glomerular filtration rate (GFR) ≤20 mL/minute/1.73 m^2 estimated by Modification of Diet in Renal Disease (MDRD) calculation.
  • Bleeding diathesis or thrombocytopenia defined as platelet count <50,000 platelets/μL.
  • Anemia defined as hemoglobin <9 g/dL, provided that there is no evidence of bleeding.
  • Known AIDS or HIV seropositive status, or a previous diagnosis of immunodeficiency with an absolute neutrophil count <1000 cells/mm^3.
  • Diagnosis of, or treatment for, any cancer other than basal cell carcinoma within the last 5 years. (Past medical history of cancer is not exclusionary as long as subject has been disease-free for at least 5 years since the time of diagnosis and treatment).
  • 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.
  • 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.
  • Pregnant or breast-feeding.
  • 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.
  • 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.

Trial locations and contacts

54 sites in 10 countries.

54 sites in 10 countries

United States29 sites

  • Study site

    Alexandria, Louisiana

  • Study site

    Augusta, Georgia

  • Study site

    Birmingham, Alabama

  • Study site

    Boston, Massachusetts

  • Study site

    Charleston, South Carolina

  • Study site

    Columbus, Ohio

  • Study site

    Germantown, Tennessee

  • Study site

    Houston, Texas

  • Study site

    Iowa City, Iowa

  • Study site

    Jacksonville, Florida

  • Study site

    Kansas City, Missouri

  • Study site

    La Jolla, California

  • Study site

    Long Beach, California

  • Study site

    Miami, Florida

  • Study site

    New York, New York

  • Study site

    Newark, Delaware

  • Study site

    Oklahoma City, Oklahoma

  • Study site

    Philadelphia, Pennsylvania

  • Study site

    Rapid City, South Dakota

  • Study site

    Salt Lake City, Utah

  • Study site

    San Antonio, Texas

  • Study site

    San Diego, California

  • Study site

    St Louis, Missouri

  • Study site

    Sylmar, California

  • Study site

    Tacoma, Washington

  • Study site

    The Bronx, New York

  • Study site

    Tullahoma, Tennessee

  • Study site

    Waukesha, Wisconsin

  • Study site

    Winston-Salem, North Carolina

Other trials in United States

Germany5 sites

  • Study site

    Bad Nauheim

  • Study site

    Berlin

  • Study site

    Cologne

  • Study site

    Dresden

  • Study site

    München

Other trials in Germany

Israel4 sites

  • Study site

    Ashkelon

  • Study site

    Holon

  • Study site

    Jerusalem

  • Study site

    Rehovot

Other trials in Israel

Denmark3 sites

  • Study site

    Aalborg

  • Study site

    Coppenhagen

  • Study site

    Hvidovre

Other trials in Denmark

Poland3 sites

  • Study site

    Gdansk

  • Study site

    Wroclaw

  • Study site

    Zabrze

Other trials in Poland

Sweden3 sites

  • Study site

    Malmö

  • Study site

    Örebrö

  • Study site

    Stockholm

Other trials in Sweden

Belgium2 sites

  • Study site

    Aalst

  • Study site

    Leuven

Other trials in Belgium

Hungary2 sites

  • Study site

    Budapest

  • Study site

    Debrecen

Other trials in Hungary

United Kingdom2 sites

  • Study site

    Glasgow

  • Study site

    London

Other trials in United Kingdom

Netherlands1 site

  • Study site

    Groningen

Other trials in Netherlands

About this study

Official title: 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

The purpose of this trial is to assess whether MYDICAR can reduce the frequency and/or delay heart failure related hospitalizations in persons with advanced heart failure when added to their maximal and optimized therapy.

Being tested
AAV1/SERCA2a (MYDICAR), Placebo
Keywords
Cardiomegaly, Heart Diseases, Cardiovascular Diseases
Medical subject headings
Heart Failure, Cardiomyopathies, Cardiomegaly, Heart Diseases, Cardiovascular Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AAV1/SERCA2a (MYDICAR)Genetic

    Single intracoronary infusion 1 x 10^13 DNase Resistant Particles (DRP) MYDICAR

  • PlaceboGenetic

    Single intracoronary infusion

Study groups in NCT01643330
Study groupRoleWhat they receive
AAV1/SERCA2a (MYDICAR)ExperimentalIntracoronary infusion
Receives: Genetic: AAV1/SERCA2a (MYDICAR)
PlaceboPlacebo comparatorIntracoronary infusion
Receives: Genetic: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Time to recurrent events (heart failure [HF]-related hospitalizations, ambulatory worsening HF) in the presence of terminal events (all-cause death, heart transplant, mechanical circulatory support device [MCSD] implantation)

    Measured: From administration up to 12 months

Secondary outcomes (1)

  1. Time-to-terminal event (all-cause death, heart transplant, MCSD implantation) in the presence of recurrent events.

    Measured: From administration up to 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Jul 2012 (estimated)
  2. Study startJul 2012
  3. Primary completionFeb 2015
  4. Study completionFeb 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
250 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01643330
Sponsor's protocol ID
CELL-004
Other IDs
2012-001700-37
Acronym
CUPID-2b
Status last verified
Feb 2016
First submitted
16 Jul 2012
Last updated
24 Mar 2016
Results posted
No
Data monitoring committee
Yes

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. doi: 10.1016/j.cardfail.2009.01.013.

    PubMed 19327618

  • 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. doi: 10.1161/CIRCULATIONAHA.111.022889. Epub 2011 Jun 27.

    PubMed 21709064

  • 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. doi: 10.1007/s10557-011-6285-9.

    PubMed 21340529

  • Zsebo K, Yaroshinsky A, Rudy JJ, Wagner K, Greenberg B, Jessup M, Hajjar RJ. Long-term effects of AAV1/SERCA2a gene transfer in patients with severe heart failure: analysis of recurrent cardiovascular events and mortality. Circ Res. 2014 Jan 3;114(1):101-8. doi: 10.1161/CIRCRESAHA.113.302421. Epub 2013 Sep 24.

    PubMed 24065463

  • Greenberg B, Butler J, Felker GM, Ponikowski P, Voors AA, Pogoda JM, Provost R, Guerrero J, Hajjar RJ, Zsebo KM. Prevalence of AAV1 neutralizing antibodies and consequences for a clinical trial of gene transfer for advanced heart failure. Gene Ther. 2016 Mar;23(3):313-9. doi: 10.1038/gt.2015.109. Epub 2015 Dec 24.

    PubMed 26699914

  • Greenberg B, Butler J, Felker GM, Ponikowski P, Voors AA, Desai AS, Barnard D, Bouchard A, Jaski B, Lyon AR, Pogoda JM, Rudy JJ, Zsebo KM. Calcium upregulation by percutaneous administration of gene therapy in patients with cardiac disease (CUPID 2): a randomised, multinational, double-blind, placebo-controlled, phase 2b trial. Lancet. 2016 Mar 19;387(10024):1178-86. doi: 10.1016/S0140-6736(16)00082-9. Epub 2016 Jan 21.

    PubMed 26803443

  • Greenberg B, Yaroshinsky A, Zsebo KM, Butler J, Felker GM, Voors AA, Rudy JJ, Wagner K, Hajjar RJ. Design of a phase 2b trial of intracoronary administration of AAV1/SERCA2a in patients with advanced heart failure: the CUPID 2 trial (calcium up-regulation by percutaneous administration of gene therapy in cardiac disease phase 2b). JACC Heart Fail. 2014 Feb;2(1):84-92. doi: 10.1016/j.jchf.2013.09.008. Epub 2014 Jan 25.

    PubMed 24622121

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing AAV1/SERCA2a (MYDICAR) in people with Ischemic Cardiomyopathy and Non-ischemic Cardiomyopathy, run by Celladon Corporation at 54 sites in 10 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 54 sites in United States, Germany, Israel, Denmark, Poland and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Time to recurrent events (heart failure [HF]-related hospitalizations, ambulatory worsening HF) in the presence of terminal events (all-cause death, heart transplant, mechanical circulatory support device [MCSD] implantation) (time frame: From administration up to 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01643330, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Mar 2016.

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