Title

Efficacy and Safety Study of Genetically Targeted Enzyme Replacement Therapy for Advanced Heart Failure
A Phase 1/2 Trial of Intracoronary Administration of MYDICAR® (AAV1/SERCA2a) in Subjects With Heart Failure in Two Stages (Open-Label, Sequential Dose-Escalation Cohorts and Randomized, Double-Blind, Placebo-Controlled, Parallel Cohorts)
  • Phase

    Phase 1/Phase 2
  • Study Type

    Interventional
  • Intervention/Treatment

    mydicar ...
  • Study Participants

    51
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.
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 complementary DNA (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 Started
Mar 31
2007
Primary Completion
Aug 31
2010
Study Completion
Aug 31
2012
Results Posted
Aug 20
2014
Estimate
Last Update
Aug 20
2014
Estimate

Genetic MYDICAR Phase 1 (Open-label, Serial Dose-Escalation Study)

MYDICAR administered by antegrade epicardial coronary artery infusion

  • Other names: AAV1/SERCA2a

Procedure Placebo Infusion

Saline; epicardial coronary artery infusion

Genetic MYDICAR Phase 2 (Placebo-controlled, Randomized Study)

MYDICAR administered by antegrade epicardial coronary artery infusion

  • Other names: AAV1/SERCA2a

MYDICAR Very Low Dose Experimental

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 1.4x10e11 DNAase resistant particles administered by antegrade epicardial coronary artery infusion. Used in MYDICAR Phase 1 (Open-label, Serial Dose-Escalation Study) only.

MYDICAR Low Dose Experimental

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 6x10e11 DNAase resistant particles administered by antegrade epicardial coronary artery infusion. Used in MYDICAR Phase 1 (Open-label, Serial Dose-Escalation Study) and MYDICAR Phase 2 (Placebo-controlled, Randomized Study)

MYDICAR Mid Dose Experimental

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 3x10e12 DNAase resistant particles administered by antegrade epicardial coronary artery infusion. Used in MYDICAR Phase 1 (Open-label, Serial Dose-Escalation Study) and MYDICAR Phase 2 (Placebo-controlled, Randomized Study).

MYDICAR High Dose Experimental

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 1x10e13 DNAase resistant particles administered by antegrade epicardial coronary artery infusion. Used in MYDICAR Phase 1 (Open-label, Serial Dose-Escalation Study) and MYDICAR Phase 2 (Placebo-controlled, Randomized Study).

Placebo infusion Placebo Comparator

A single dose of placebo (Sodium Chloride Injection, USP) administered by antegrade epicardial coronary artery infusion.

Criteria

Inclusion Criteria:

Chronic 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.
Left ventricular ejection fraction (LVEF) ≤35%
Diagnosis of New York Heart Association (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 (alanine aminotransferase [ALT], aspartate aminotransferase [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

Summary

MYDICAR® Very Low Dose

MYDICAR® Low Dose

MYDICAR® Mid Dose

MYDICAR® High Dose

Placebo

All Events

Event Type Organ System Event Term MYDICAR® Very Low Dose MYDICAR® Low Dose MYDICAR® Mid Dose MYDICAR® High Dose Placebo

Phase 2: Change in Absolute Levels of N-terminal Prohormone Brain Natriuretic Peptide (NT-proBNP) From Baseline to Month 6

NT-proBNP is a biomarker for heart failure. Increased levels of this biomarker are associated with increased mortality and cardiovascular hospitalization in patients with heart failure.

MYDICAR® Low Dose

694.1
pg/mL (Mean)
Standard Deviation: 1444.94

MYDICAR® Mid Dose

2073.1
pg/mL (Mean)
Standard Deviation: 4224.22

MYDICAR® High Dose

-13.5
pg/mL (Mean)
Standard Deviation: 928.48

Placebo

5540.0
pg/mL (Mean)
Standard Deviation: 11,873.46

Phase 2: Change in Absolute Left Ventricular End Systolic Volume (LVESV) Frm Baseline to Month 6

Contrast echocardiography was used to determine LVESV. Decreases in LVESV are associated with reduced mortality. Changes from baseline with positive values indicate a worsening in heart function and changes from baseline with negative values indicate an improvement in symptoms.

MYDICAR® Low Dose

0.4
mL (Mean)
Standard Deviation: 26.16

MYDICAR® Mid Dose

10.5
mL (Mean)
Standard Deviation: 45.91

MYDICAR® High Dose

-9.6
mL (Mean)
Standard Deviation: 27.55

Placebo

18.2
mL (Mean)
Standard Deviation: 39.45

Phase 2: Incidence of Treatment-emergent Adverse Events (TEAE) at 12 Months

Includes all adverse events that occurred from the time of first infusion of the investigational product or placebo to the 12-month visit. The category of "TEAEs related to the investigational product (IP)" includes TEAEs considered by the investigator to be possibly, probably, or definitely related to the IP.

MYDICAR® Low Dose

Any TEAE

100.0
percentage of participants

Serious TEAEs

62.5
percentage of participants

Serious TEAEs related to IP administration

Serious TEAEs related to the IP

TEAEs related to administration of the IP

12.5
percentage of participants

TEAEs related to the investigational product (IP)

50.0
percentage of participants

MYDICAR® Mid Dose

Any TEAE

100.0
percentage of participants

Serious TEAEs

50.0
percentage of participants

Serious TEAEs related to IP administration

Serious TEAEs related to the IP

TEAEs related to administration of the IP

25.0
percentage of participants

TEAEs related to the investigational product (IP)

12.5
percentage of participants

MYDICAR® High Dose

Any TEAE

88.9
percentage of participants

Serious TEAEs

33.3
percentage of participants

Serious TEAEs related to IP administration

Serious TEAEs related to the IP

TEAEs related to administration of the IP

11.1
percentage of participants

TEAEs related to the investigational product (IP)

11.1
percentage of participants

Placebo

Any TEAE

92.9
percentage of participants

Serious TEAEs

64.3
percentage of participants

Serious TEAEs related to IP administration

28.6
percentage of participants

Serious TEAEs related to the IP

21.4
percentage of participants

TEAEs related to administration of the IP

57.1
percentage of participants

TEAEs related to the investigational product (IP)

57.1
percentage of participants

Phase 2: Length of Cardiovascular-related Hospitalizations at 6 Months

Mean number of days in the hospital for cardiovascular-related complications. All hospitalizations were evaluated and classified by the blinded Clinical Endpoints Committee.

MYDICAR® Low Dose

0.3
days (Mean)
Standard Deviation: 0.46

MYDICAR® Mid Dose

1.3
days (Mean)
Standard Deviation: 2.55

MYDICAR® High Dose

0.2
days (Mean)
Standard Deviation: 0.67

Placebo

2.1
days (Mean)
Standard Deviation: 2.92

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

Contrast echocardiography was used to determine LVEF. Increases in LVEF are associated with reduced mortality. Changes from baseline with positive values indicate an improvement in heart function and changes from baseline with negative values indicate a worsening of heart function.

MYDICAR® Low Dose

MYDICAR® Mid Dose

-1.5
Percentage of blood ejected from the LV (Mean)
Standard Deviation: 6.35

MYDICAR® High Dose

-0.7
Percentage of blood ejected from the LV (Mean)
Standard Deviation: 3.76

Placebo

-2.1
Percentage of blood ejected from the LV (Mean)
Standard Deviation: 6.90

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

NYHA classification is a symptomatic assessment in which the investigator evaluates subjects on a scale ranging from Class I (subjects with no limitation of activities, no symptoms from ordinary activities) to Class IV (subjects who should be at complete rest, confined to bed or chair; any physical activity brings on discomfort and symptoms occur at rest). The MLWHFQ is a patient-reported quality of life (QoL) measure in which patients assess the impact of their heart condition on activities in the past month using a Likert scale ranging from 0 (no effect) to 5 (very much effect). Higher scores thus indicate a lower QoL. The maximum (worst) score is 105 and the minimum (best) score is 0. For both measures, changes from baseline with positive values indicate a worsening in symptoms and changes from baseline with negative values indicate an improvement in symptoms.

MYDICAR® Low Dose

Change in MLWHFQ score

-7.6
units on a scale (Mean)
Standard Deviation: 20.99

Change in NHYA class

-0.8
units on a scale (Mean)
Standard Deviation: 0.71

MYDICAR® Mid Dose

Change in MLWHFQ score

7.9
units on a scale (Mean)
Standard Deviation: 27.28

Change in NHYA class

-0.8
units on a scale (Mean)
Standard Deviation: 0.89

MYDICAR® High Dose

Change in MLWHFQ score

-10.3
units on a scale (Mean)
Standard Deviation: 12.21

Change in NHYA class

-0.6
units on a scale (Mean)
Standard Deviation: 0.73

Placebo

Change in MLWHFQ score

3.4
units on a scale (Mean)
Standard Deviation: 36.00

Change in NHYA class

-0.2
units on a scale (Mean)
Standard Deviation: 0.70

Phase 2: Change in 6-minute Walk Test (6MWT) From Baseline to Month 6

The 6MWT measures the distance walked in meters during a 6-minute test. Higher values indicate a better functional status. Changes from baseline with negative values indicate a worsening in function and changes from baseline with positive values indicate an improvement in function.

MYDICAR® Low Dose

13.0
meters (Mean)
Standard Deviation: 61.40

MYDICAR® Mid Dose

-59.5
meters (Mean)
Standard Deviation: 213.64

MYDICAR® High Dose

1.0
meters (Mean)
Standard Deviation: 99.69

Placebo

-86.6
meters (Mean)
Standard Deviation: 164.30

Phase 2: Change in Peak Maximum Oxygen Consumption (VO2) From Baseline to Month 6

Peak VO2 is a measure of maximal oxygen consumption during cardiopulmonary exercise testing; this study used the modified Naughton treadmill protocol. Higher values indicate a better functional status. Changes from baseline with negative values indicate a worsening in function and changes from baseline with positive values indicate an improvement in function.

MYDICAR® Low Dose

-0.73
mL/kg per minute (Mean)
Standard Deviation: 4.88

MYDICAR® Mid Dose

-1.07
mL/kg per minute (Mean)
Standard Deviation: 5.076

MYDICAR® High Dose

-0.43
mL/kg per minute (Mean)
Standard Deviation: 0,802

Placebo

-2.1
mL/kg per minute (Mean)
Standard Deviation: 4.462

Phase 2: Selected Clinical Outcomes During 12-month Study Period

Incidences of key clinical endpoints as adjudicated by the blinded Clinical Endpoint Committee.

MYDICAR® Low Dose

Fatal cardiovascular event

12.5
percentage of participants

Heart failure-related hospitalization

50.0
percentage of participants

Heart transplant

Myocardial infarction

Receipt of left ventricular assist device

Silent myocardial infarction

Worsening heart failure

50.0
percentage of participants

MYDICAR® Mid Dose

Fatal cardiovascular event

Heart failure-related hospitalization

37.5
percentage of participants

Heart transplant

25.0
percentage of participants

Myocardial infarction

Receipt of left ventricular assist device

12.5
percentage of participants

Silent myocardial infarction

Worsening heart failure

37.5
percentage of participants

MYDICAR® High Dose

Fatal cardiovascular event

Heart failure-related hospitalization

22.2
percentage of participants

Heart transplant

11.1
percentage of participants

Myocardial infarction

Receipt of left ventricular assist device

Silent myocardial infarction

Worsening heart failure

22.2
percentage of participants

Placebo

Fatal cardiovascular event

7.1
percentage of participants

Heart failure-related hospitalization

42.9
percentage of participants

Heart transplant

7.1
percentage of participants

Myocardial infarction

14.3
percentage of participants

Receipt of left ventricular assist device

14.3
percentage of participants

Silent myocardial infarction

Worsening heart failure

50.0
percentage of participants

Phase 2: Length of Cardiovascular-related Hospitalizations at 12 Months

Mean number of days in the hospital for cardiovascular-related complications. All hospitalizations were evaluated and classified by the blinded Clinical Endpoints Committee.

MYDICAR® Low Dose

10.1
days (Mean)
Standard Deviation: 12.71

MYDICAR® Mid Dose

7.4
days (Mean)
Standard Deviation: 11.80

MYDICAR® High Dose

0.4
days (Mean)
Standard Deviation: 1.33

Placebo

4.5
days (Mean)
Standard Deviation: 5.80

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

NYHA classification is a symptomatic assessment in which the investigator evaluates subjects on a scale ranging from Class I (subjects with no limitation of activities, no symptoms from ordinary activities) to Class IV (subjects who should be at complete rest, confined to bed or chair; any physical activity brings on discomfort and symptoms occur at rest). The MLWHFQ is a patient-reported quality of life (QoL) measure in which patients assess the impact of their heart condition on activities in the past month using a Likert scale ranging from 0 (no effect) to 5 (very much effect). Higher scores thus indicate a lower QoL. The maximum (worst) score is 105 and the minimum (best) score is 0. For both measures, changes from baseline with positive values indicate a worsening in symptoms and changes from baseline with negative values indicate an improvement in symptoms.

MYDICAR® Low Dose

Change in MLWHFQ score

24.4
units on a scale (Mean)
Standard Deviation: 37.3

Change in NHYA class

-0.1
units on a scale (Mean)
Standard Deviation: 0.99

MYDICAR® Mid Dose

Change in MLWHFQ score

22.5
units on a scale (Mean)
Standard Deviation: 32.56

Change in NHYA class

0.1
units on a scale (Mean)
Standard Deviation: 0.83

MYDICAR® High Dose

Change in MLWHFQ score

0.1
units on a scale (Mean)
Standard Deviation: 23.80

Change in NHYA class

-0.3
units on a scale (Mean)
Standard Deviation: 0.71

Placebo

Change in MLWHFQ score

14.7
units on a scale (Mean)
Standard Deviation: 34.89

Change in NHYA class

0.1
units on a scale (Mean)
Standard Deviation: 0.73

Phase 2: Change in 6-minute Walk Test (6MWT) From Baseline to Month 12

The 6MWT measures the distance walked in meters during a 6-minute test. Higher values indicate a better functional status. Changes from baseline with negative values indicate a worsening in function and changes from baseline with positive values indicate an improvement in function.

MYDICAR® Low Dose

-167.9
meters (Mean)
Standard Deviation: 191.02

MYDICAR® Mid Dose

-115.9
meters (Mean)
Standard Deviation: 226.56

MYDICAR® High Dose

-23.7
meters (Mean)
Standard Deviation: 151.08

Placebo

-120.4
meters (Mean)
Standard Deviation: 181.41

Phase 2: Change in Peak Maximum Oxygen Consumption (VO2) From Baseline to Month 12

Peak VO2 is a measure of maximal oxygen consumption during cardiopulmonary exercise testing; this study used the modified Naughton treadmill protocol. Higher values indicate a better functional status. Changes from baseline with negative values indicate a worsening in function and changes from baseline with positive values indicate an improvement in function.

MYDICAR® Low Dose

-5.0
mL/kg per minute (Mean)
Standard Deviation: 4.733

MYDICAR® Mid Dose

-3.31
mL/kg per minute (Mean)
Standard Deviation: 5.473

MYDICAR® High Dose

-1.57
mL/kg per minute (Mean)
Standard Deviation: 3.677

Placebo

-2.75
mL/kg per minute (Mean)
Standard Deviation: 5.084

Phase 2: Change in Absolute Levels of N-terminal Prohormone Brain Natriuretic Peptide (NT-proBNP) From Baseline to Month 12

NT-proBNP is a biomarker for heart failure. Increased levels of this biomarker are associated with increased mortality and cardiovascular hospitalization in patients with heart failure.

MYDICAR® Low Dose

3689.1
pg/mL (Mean)
Standard Deviation: 5109.27

MYDICAR® Mid Dose

8440.4
pg/mL (Mean)
Standard Deviation: 11270.44

MYDICAR® High Dose

1756.3
pg/mL (Mean)
Standard Deviation: 4331.00

Placebo

11464.3
pg/mL (Mean)
Standard Deviation: 16866.55

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

Contrast echocardiography was used to determine LVEF. Increases in LVEF are associated with reduced mortality. Changes from baseline with positive values indicate an improvement in heart function and changes from baseline with negative values indicate a worsening of heart function.

MYDICAR® Low Dose

-6.5
Percentage of blood ejected from the LV (Mean)
Standard Deviation: 7.26

MYDICAR® Mid Dose

-5.6
Percentage of blood ejected from the LV (Mean)
Standard Deviation: 10.52

MYDICAR® High Dose

0.3
Percentage of blood ejected from the LV (Mean)
Standard Deviation: 8.87

Placebo

-2.5
Percentage of blood ejected from the LV (Mean)
Standard Deviation: 9.96

Phase 2: Change in Absolute Left Ventricular End Systolic Volume (LVESV) From Baseline to Month 12

Contrast echocardiography was used to determine LVESV. Decreases in LVESV are associated with reduced mortality. Changes from baseline with positive values indicate a worsening in heart function and changes from baseline with negative values indicate an improvement in symptoms.

MYDICAR® Low Dose

40.7
mL (Mean)
Standard Deviation: 59.79

MYDICAR® Mid Dose

66.8
mL (Mean)
Standard Deviation: 103.12

MYDICAR® High Dose

9.9
mL (Mean)
Standard Deviation: 49.27

Placebo

37.7
mL (Mean)
Standard Deviation: 69.09

Phase 1 and Phase 2: All Subject Deaths Through 36 Months

All subject deaths that occurred during the 12-month study or the 24-month follow-up in subjects enrolled in either the Phase 1 or Phase 2 trial. Events occurring after early termination from the trial are listed as occurring during long-term follow-up, but may have been within 12 months. Specifically, two cardiovascular (CV) deaths in placebo subjects occurred following early study termination, but within 12 months of study initiation. These deaths are therefore included under "Deaths within 12 months" but also listed as "Cardiovascular deaths in long-term follow-up." Accordingly, the number of "Cardiovascular deaths in long-term follow-up" for the placebo group is greater than the number of "Deaths after 12 months," as 2 of the deaths occurred within 12 months but after early termination.

MYDICAR® Very Low Dose

All deaths during 36 months

1.0
participants

Cardiovascular deaths in long-term follow-up

1.0
participants

Cardiovascular deaths on study

Deaths after 12 months

1.0
participants

Deaths within 12 months

MYDICAR® Low Dose

All deaths during 36 months

4.0
participants

Cardiovascular deaths in long-term follow-up

2.0
participants

Cardiovascular deaths on study

2.0
participants

Deaths after 12 months

2.0
participants

Deaths within 12 months

2.0
participants

MYDICAR® Mid Dose

All deaths during 36 months

3.0
participants

Cardiovascular deaths in long-term follow-up

1.0
participants

Cardiovascular deaths on study

Deaths after 12 months

3.0
participants

Deaths within 12 months

MYDICAR® High Dose

All deaths during 36 months

2.0
participants

Cardiovascular deaths in long-term follow-up

2.0
participants

Cardiovascular deaths on study

Deaths after 12 months

2.0
participants

Deaths within 12 months

All MYDICAR®

All deaths during 36 months

10.0
participants

Cardiovascular deaths in long-term follow-up

6.0
participants

Cardiovascular deaths on study

2.0
participants

Deaths after 12 months

8.0
participants

Deaths within 12 months

2.0
participants

Placebo

All deaths during 36 months

6.0
participants

Cardiovascular deaths in long-term follow-up

4.0
participants

Cardiovascular deaths on study

1.0
participants

Deaths after 12 months

3.0
participants

Deaths within 12 months

3.0
participants

Total

51
Participants

Age, Continuous

60.5
years (Mean)
Standard Deviation: 11.39

Race (NIH/OMB)

Sex: Female, Male

Phase I: Open-label Dose-escalation

MYDICAR® Very Low Dose

MYDICAR® Low Dose

MYDICAR® Mid Dose

MYDICAR® High Dose

Phase 2: Randomized Double-blind

MYDICAR® Low Dose

MYDICAR® Mid Dose

MYDICAR® High Dose

Placebo

Drop/Withdrawal Reasons

MYDICAR® Very Low Dose

MYDICAR® Low Dose

MYDICAR® Mid Dose

MYDICAR® High Dose

Placebo