Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43870   clinical trials with a EudraCT protocol, of which   7289   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2012-001700-37
    Sponsor's Protocol Code Number:CELL-004-A1
    National Competent Authority:Denmark - DHMA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2012-10-01
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedDenmark - DHMA
    A.2EudraCT number2012-001700-37
    A.3Full title of the trial
    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
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    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
    A.3.2Name or abbreviated title of the trial where available
    CUPID Phase 2b Trial
    A.4.1Sponsor's protocol code numberCELL-004-A1
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorCelladon Corporation
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportCelladon Corporation
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationCelladon Corporation
    B.5.2Functional name of contact pointVice President, Clinical Operations
    B.5.3 Address:
    B.5.3.1Street Address11988 El Camino Real, Suite 650
    B.5.3.2Town/ citySan Diego, California
    B.5.3.3Post code92130-3579
    B.5.3.4CountryUnited States
    B.5.4Telephone number18583664288
    B.5.5Fax number18589640974
    B.5.6E-mailjrudy@celladon.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameMYDICAR® Injection
    D.3.2Product code AAV1/SERCA2a
    D.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntracoronary use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNAAV1/SERCA2a
    D.3.9.2Current sponsor codeAAV1/SERCA2a
    D.3.10 Strength
    D.3.10.1Concentration unit Other
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10000000000000
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) Yes
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product Yes
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms Yes
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for injection
    D.8.4Route of administration of the placeboIntracoronary use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Moderate to advanced heart failure (NYHA classII, III or IV) due to systolic dysfunction
    E.1.1.1Medical condition in easily understood language
    Advanced heart failure
    E.1.1.2Therapeutic area Diseases [C] - Cardiovascular Diseases [C14]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.0
    E.1.2Level LLT
    E.1.2Classification code 10010684
    E.1.2Term Congestive heart failure
    E.1.2System Organ Class 100000004849
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Determine the efficacy of a single intracoronary infusion of 1 x 10e13 DNase Resistant Particles (DRP) MYDICAR® (AAV1/SERCA2a) added to an optimal HF regimen in patients with ischemic or non-ischemic cardiomyopathy and moderate to advanced symptoms of heart failure (HF) by reducing the frequency and/or delaying HF-related hospitalizations and ambulatory worsening HF (recurrent events) compared to placebo-treated patients
    E.2.2Secondary objectives of the trial
    Assessment of the safety of MYDICAR® by determining the incidence and severity of AEs and changes in laboratory parameters
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Negative neutralizing AAV1 antibodies (NAb) (titer <1:2 or equivocal) 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 non-ischemic 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 IMP.
    a. Hypertrophic cardiomyopathy is excluded.
    b. Toxic and 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.
    4. Left ventricular ejection fraction (LVEF) ≤35% anytime during the 60-day window prior to administration of IMP.
    5. Diagnosis of NYHA class II, III or IV heart failure for a minimum of 90 days prior to screening.
    6. Individualized, 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 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.
    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 IMP 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 IMP. 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 IMP.
    8. Ability to understand and comply with study requirements as evidenced by providing signed written informed consent form and Release of Medical Information Form.
    9. Presence of at least one of the following risk factors:
    a. 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)
    b. 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
    10.In Germany only: Medically indicated for diagnostic angiography at the clinician’s discretion.
    E.4Principal exclusion criteria
    1.Any intravenous (IV) therapy with positive inotropes, vasodilators or diuretics within 30 days prior to screening.
    2. Restrictive cardiomyopathy, obstructive cardiomyopathy, acute myocarditis, pericardial disease, amyloidosis, infiltrative cardiomyopathy, uncorrected thyroid disease or discrete LV aneurysm.
    3. Cardiac surgery, percutaneous coronary intervention (PCI) 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. Large non-STEMI shall be defined >3x ULN for CK-MB or >5x ULN for troponin.
    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 IMP 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 <9 g/dL, provided that there is no evidence of bleeding.
    14. Known AIDS or HIV seropositive status, or a previous diagnosis of immunodeficiency with an absolute neutrophil count <1000 cells/mm3.
    15. 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).
    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 medicinal product administration. If an infection does occur, defer infusion for up to 28 days until resolved.
    - Significant left main or ostial right coronary artery disease, noted
    during pre-infusion angiography, requiring immediate intervention.
    - No major coronary artery with TIMI grade 3 flow.
    - Inability to position the coronary catheters in the coronary ostia in a safe and stable manner.
    E.5 End points
    E.5.1Primary end point(s)
    The primary efficacy endpoint is the time to recurrent events (hospitalizations related to failure of the native heart that has not been implanted with a mechanical circulatory support device (LVAD, RVAD, BiVAD, TAH and referred to generically as "MCSD")) and ambulatory worsening failure of the native heart that has not been implanted with a MCSD in the presence of terminal events (all-cause death, heart transplant, MCSD implantation) based on the joint frailty model.
    Efficacy will be further assessed by a secondary analysis involving the primary endpoint based on various definitions of the study population (ITT, modified ITT excluding AAV1 NAb positive and equivocal 1:2 patients, and per-protocol (PP)). In addition, sensitivity analyses will be done using various recurrent and terminal event definitions and different methods of statistical analysis to assure that study outcome is not due to a specific statistical method or event definition. Analyses of the following endpoints will be included in sensitivity analyses: time-to-first clinical event, defined as all-cause death, heart transplant, MCSD implantation, HF-related hospitalization, and ambulatory worsening HF; and the average rate and duration of HF-related / CV-related / all-cause hospitalizations over time on study.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Analyses will be performed when a minimum length of time and cumulative total number of clinical events have happened. Unless discontinued for a terminal event, all subjects must have completed the full 12-Month Active Observation Period. Most safety parameters will be collected only during the 12-Month Active Observation period. Information about hospitalizations, new medical conditions, HF status and long-term survival will be collected through the end of the Long- Term Follow-Up Period.
    E.5.2Secondary end point(s)
    The secondary efficacy endpoint is time to terminal event, defined as all- cause death, heart transplant or MCSD implantation, based on the joint frailty model and performed simultaneously with the primary endpoint analysis. Secondary and sensitivity analyses for this secondary endpoint will include the following: various definitions of the study population, time-to-all-cause death analysis and a statistical approach based on traditional survival analysis (product-limit point estimates and the log rank test).
    E.5.2.1Timepoint(s) of evaluation of this end point
    Analyses will be performed when a minimum length of time and cumulative total number of clinical events have happened. Unless discontinued for a terminal event, all subjects must have completed the full 12-Month Active Observation Period. Most safety parameters will be collected only during the 12-Month Active Observation period. Information about hospitalizations, new medical conditions, HF status and long-term survival will be collected through the end of the Long- Term Follow-Up Period.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic Yes
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned5
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA34
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Belgium
    Czech Republic
    Denmark
    Germany
    Hungary
    Israel
    Netherlands
    Poland
    Sweden
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    The End of Study is when all subjects have been observed and followed for a minimum cumulative total of 24 months or until the Primary Analysis Data Cutoff, whichever occurs later, unless terminated early for any reason.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months6
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 50
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 200
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state40
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 100
    F.4.2.2In the whole clinical trial 250
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    According to expected normal treatment of advanced heart failure
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2012-10-01
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2012-10-10
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2016-02-26
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Tue Apr 30 13:50:44 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA