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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 has been completed.
Sponsor:
Information provided by (Responsible Party):
Celladon Corporation
ClinicalTrials.gov Identifier:
NCT00454818
First received: March 30, 2007
Last updated: August 19, 2014
Last verified: August 2014
Results First Received: June 25, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions: Heart Failure, Congestive
Dilated Cardiomyopathy
Interventions: Genetic: MYDICAR Phase 1 (Open-label, Serial Dose-Escalation Study)
Procedure: Placebo Infusion
Genetic: MYDICAR Phase 2 (Placebo-controlled, Randomized Study)

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
MYDICAR® Very Low Dose

Single dose of MYDICAR®, a viral vector (adeno-associated virus serotype 1 [AAV1]) carrying the gene for sarcoplasmic reticulum Ca++-adenosine triphosphatase (SERCA2a), at a dose of 1.4E11 DNAase resistant particles (DRP) administered by antegrade epicardial coronary artery infusion.

This arm was included only in the Phase I open-label dose-escalation period.

MYDICAR® Low Dose Single dose of MYDICAR®, a viral vector (adeno-associated virus serotype 1 [AAV1]) carrying the gene for sarcoplasmic reticulum Ca++-adenosine triphosphatase (SERCA2a), at a dose of 6E11 DNAase resistant particles (DRP) administered by antegrade epicardial coronary artery infusion.
MYDICAR® Mid Dose Single dose of MYDICAR®, a viral vector (adeno-associated virus serotype 1 [AAV1]) carrying the gene for sarcoplasmic reticulum Ca++-adenosine triphosphatase (SERCA2a), at a dose of 3E12 DNAase resistant particles (DRP) administered by antegrade epicardial coronary artery infusion.
MYDICAR® High Dose Single dose of MYDICAR®, a viral vector (adeno-associated virus serotype 1 [AAV1]) carrying the gene for sarcoplasmic reticulum Ca++-adenosine triphosphatase (SERCA2a), at a dose of 1E13 DNAase resistant particles (DRP) administered by antegrade epicardial coronary artery infusion.
Placebo

Single dose of placebo administered by antegrade epicardial coronary artery infusion.

The placebo arm was included only in the Phase 2 randomized double-blind period.


Participant Flow for 2 periods

Period 1:   Phase I: Open-label Dose-escalation
    MYDICAR® Very Low Dose     MYDICAR® Low Dose     MYDICAR® Mid Dose     MYDICAR® High Dose     Placebo  
STARTED     3     3     3     3     0  
COMPLETED     2     2     2     2     0  
NOT COMPLETED     1     1     1     1     0  
Received heart transplant                 1                 0                 0                 0                 0  
Death                 0                 1                 0                 0                 0  
Received left ventricular assist device                 0                 0                 1                 1                 0  

Period 2:   Phase 2: Randomized Double-blind
    MYDICAR® Very Low Dose     MYDICAR® Low Dose     MYDICAR® Mid Dose     MYDICAR® High Dose     Placebo  
STARTED     0     8     8     9     14  
COMPLETED     0     6     5     8     10  
NOT COMPLETED     0     2     3     1     4  
Received milrinone or dobutamine                 0                 1                 0                 1                 0  
Death                 0                 1                 0                 0                 1  
Received a heart transplant                 0                 0                 2                 0                 1  
Received left ventricular assist device                 0                 0                 1                 0                 2  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Baseline data are provided for subjects enrolled in the Phase 1 or Phase 2 trials.

Reporting Groups
  Description
Phase 1: MYDICAR® Very Low Dose Single dose of MYDICAR®, a viral vector (adeno-associated virus serotype 1 [AAV1]) carrying the gene for sarcoplasmic reticulum Ca++-adenosine triphosphatase (SERCA2a), at a dose of 1.4E11 DRP administered by antegrade epicardial coronary artery infusion.
Phase 1: MYDICAR® Low Dose Single dose of MYDICAR®, a viral vector (adeno-associated virus serotype 1 [AAV1]) carrying the gene for sarcoplasmic reticulum Ca++-adenosine triphosphatase (SERCA2a), at a dose of 6E11 DRP administered by antegrade epicardial coronary artery infusion.
Phase 1: MYDICAR® Mid Dose Single dose of MYDICAR®, a viral vector (adeno-associated virus serotype 1 [AAV1]) carrying the gene for sarcoplasmic reticulum Ca++-adenosine triphosphatase (SERCA2a), at a dose of 3E12 DRP administered by antegrade epicardial coronary artery infusion.
Phase 1: MYDICAR® High Dose Single dose of MYDICAR®, a viral vector (adeno-associated virus serotype 1 [AAV1]) carrying the gene for sarcoplasmic reticulum Ca++-adenosine triphosphatase (SERCA2a), at a dose of 1E13 DRP administered by antegrade epicardial coronary artery infusion.
Phase 2: MYDICAR® Low Dose Single dose of MYDICAR®, a viral vector (adeno-associated virus serotype 1 [AAV1]) carrying the gene for sarcoplasmic reticulum Ca++-adenosine triphosphatase (SERCA2a), at a dose of 6E11 DRP administered by antegrade epicardial coronary artery infusion.
Phase 2: MYDICAR® Mid Dose Single dose of MYDICAR®, a viral vector (adeno-associated virus serotype 1 [AAV1]) carrying the gene for sarcoplasmic reticulum Ca++-adenosine triphosphatase (SERCA2a), at a dose of 3E12 DRP administered by antegrade epicardial coronary artery infusion.
Phase 2: MYDICAR® High Dose Single dose of MYDICAR®, a viral vector (adeno-associated virus serotype 1 [AAV1]) carrying the gene for sarcoplasmic reticulum Ca++-adenosine triphosphatase (SERCA2a), at a dose of 1E13 DRP administered by antegrade epicardial coronary artery infusion.
Phase 2: Placebo Single dose of placebo administered by antegrade epicardial coronary artery infusion.
Total Total of all reporting groups

Baseline Measures
    Phase 1: MYDICAR® Very Low Dose     Phase 1: MYDICAR® Low Dose     Phase 1: MYDICAR® Mid Dose     Phase 1: MYDICAR® High Dose     Phase 2: MYDICAR® Low Dose     Phase 2: MYDICAR® Mid Dose     Phase 2: MYDICAR® High Dose     Phase 2: Placebo     Total  
Number of Participants  
[units: participants]
  3     3     3     3     8     8     9     14     51  
Age  
[units: years]
Mean ± Standard Deviation
  53.7  ± 7.02     55.7  ± 4.51     48.0  ± 8.54     58.77  ± 19.01     60.3  ± 10.27     63.9  ± 8.85     56.6  ± 13.96     61.0  ± 11.94     60.5  ± 11.39  
Gender  
[units: participants]
                 
Female     0     1     1     1     1     0     3     1     8  
Male     3     2     2     2     7     8     6     13     43  
Race (NIH/OMB)  
[units: participants]
                 
American Indian or Alaska Native     0     0     0     0     0     0     0     0     0  
Asian     0     0     0     0     0     0     0     0     0  
Native Hawaiian or Other Pacific Islander     0     0     0     0     0     0     0     0     0  
Black or African American     0     0     2     0     0     0     3     1     6  
White     3     3     1     3     8     8     6     13     45  
More than one race     0     0     0     0     0     0     0     0     0  
Unknown or Not Reported     0     0     0     0     0     0     0     0     0  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Phase 2: Incidence of Treatment-emergent Adverse Events (TEAE) at 12 Months   [ Time Frame: 12 months ]

2.  Primary:   Phase 2: Length of Cardiovascular-related Hospitalizations at 6 Months   [ Time Frame: 6 months ]

3.  Primary:   Phase 2: Change in Symptomatic Efficacy Domains From Baseline to Month 6: New York Heart Association (NYHA) Class and Minnesota Living With Heart Failure Questionnaire (MLWHFQ) Score   [ Time Frame: Baseline to 6 months ]

4.  Primary:   Phase 2: Change in 6-minute Walk Test (6MWT) From Baseline to Month 6   [ Time Frame: Baseline to 6 months ]

5.  Primary:   Phase 2: Change in Peak Maximum Oxygen Consumption (VO2) From Baseline to Month 6   [ Time Frame: Baseline to 6 months ]

6.  Primary:   Phase 2: Change in Absolute Levels of N-terminal Prohormone Brain Natriuretic Peptide (NT-proBNP) From Baseline to Month 6   [ Time Frame: Baseline to 6 months ]

7.  Primary:   Phase 2: Change in Percentage of Blood Ejected From the Left Ventricle (LV) (i.e., Left Ventricular Ejection Fraction [LVEF]) From Baseline to Month 6   [ Time Frame: Baseline to 6 months ]

8.  Primary:   Phase 2: Change in Absolute Left Ventricular End Systolic Volume (LVESV) Frm Baseline to Month 6   [ Time Frame: Baseline to 6 months ]

9.  Other Pre-specified:   Phase 2: Length of Cardiovascular-related Hospitalizations at 12 Months   [ Time Frame: 12 months ]

10.  Other Pre-specified:   Phase 2: Change in Symptomatic Efficacy Domains From Baseline to Month 12: New York Heart Association (NYHA) Class and Minnesota Living With Heart Failure Questionnaire (MLWHFQ) Score   [ Time Frame: Baseline to 12 months ]

11.  Other Pre-specified:   Phase 2: Change in 6-minute Walk Test (6MWT) From Baseline to Month 12   [ Time Frame: Baseline to 12 months ]

12.  Other Pre-specified:   Phase 2: Change in Peak Maximum Oxygen Consumption (VO2) From Baseline to Month 12   [ Time Frame: Baseline to 12 months ]

13.  Other Pre-specified:   Phase 2: Change in Absolute Levels of N-terminal Prohormone Brain Natriuretic Peptide (NT-proBNP) From Baseline to Month 12   [ Time Frame: Baseline to 12 months ]

14.  Post-Hoc:   Phase 2: Selected Clinical Outcomes During 12-month Study Period   [ Time Frame: 12 months ]

15.  Other Pre-specified:   Phase 2: Change in Percentage of Blood Ejected From the Left Ventricle (LV) (i.e., Left Ventricular Ejection Fraction [LVEF]) From Baseline to Month 12   [ Time Frame: Baseline to 12 months ]

16.  Other Pre-specified:   Phase 2: Change in Absolute Left Ventricular End Systolic Volume (LVESV) From Baseline to Month 12   [ Time Frame: Baseline to 12 months ]

17.  Other Pre-specified:   Phase 1 and Phase 2: All Subject Deaths Through 36 Months   [ Time Frame: 36 months ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Limitations of this study include its small sample size and the inability to conclusively prove that the delivered gene was responsible for the observed clinical effects. Larger confirmatory trials are needed.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Jeffrey J. Rudy, Vice President
Organization: Celladon Corporation
phone: 1 858-366-4288
e-mail: jrudy@celladon.net


Publications of Results:
Other Publications:
Publications automatically indexed to this study:

Responsible Party: Celladon Corporation
ClinicalTrials.gov Identifier: NCT00454818     History of Changes
Other Study ID Numbers: CELL-001, CUPID Trial
Study First Received: March 30, 2007
Results First Received: June 25, 2014
Last Updated: August 19, 2014
Health Authority: United States: Food and Drug Administration