Dilated Cardiomyopathy, Heart Failure, Congestive
Conditions
Brief summary
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.
Detailed description
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.
Interventions
GENETICMYDICAR Phase 1 (Open-label, Serial Dose-Escalation Study)
MYDICAR administered by antegrade epicardial coronary artery infusion
PROCEDUREPlacebo Infusion
Saline; epicardial coronary artery infusion
GENETICMYDICAR Phase 2 (Placebo-controlled, Randomized Study)
MYDICAR administered by antegrade epicardial coronary artery infusion
Sponsors
Celladon Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 2: Change in Absolute Left Ventricular End Systolic Volume (LVESV) Frm Baseline to Month 6 | Baseline to 6 months | 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. |
| Phase 2: Incidence of Treatment-emergent Adverse Events (TEAE) at 12 Months | 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. |
| Phase 2: Length of Cardiovascular-related Hospitalizations at 6 Months | 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. |
| 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 | Baseline to 6 months | 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. |
| Phase 2: Change in 6-minute Walk Test (6MWT) From Baseline to Month 6 | Baseline to 6 months | 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. |
| Phase 2: Change in Peak Maximum Oxygen Consumption (VO2) From Baseline to Month 6 | Baseline to 6 months | 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. |
| Phase 2: Change in Absolute Levels of N-terminal Prohormone Brain Natriuretic Peptide (NT-proBNP) From Baseline to Month 6 | Baseline to 6 months | 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. |
| 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 | Baseline to 6 months | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Phase 2: Length of Cardiovascular-related Hospitalizations at 12 Months | 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. |
| 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 | Baseline to 12 months | 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. |
| Phase 2: Change in 6-minute Walk Test (6MWT) From Baseline to Month 12 | Baseline to 12 months | 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. |
| Phase 2: Change in Peak Maximum Oxygen Consumption (VO2) From Baseline to Month 12 | Baseline to 12 months | 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. |
| Phase 2: Change in Absolute Levels of N-terminal Prohormone Brain Natriuretic Peptide (NT-proBNP) From Baseline to Month 12 | Baseline to 12 months | 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. |
| 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 | Baseline to 12 months | 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. |
| Phase 2: Change in Absolute Left Ventricular End Systolic Volume (LVESV) From Baseline to Month 12 | Baseline to 12 months | 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. |
| Phase 1 and Phase 2: All Subject Deaths Through 36 Months | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 3 |
| 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. | 3 |
| 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. | 3 |
| 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. | 3 |
| 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. | 8 |
| 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. | 8 |
| 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. | 9 |
| Phase 2: Placebo Single dose of placebo administered by antegrade epicardial coronary artery infusion. | 14 |
| Total | 51 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Phase 2: Randomized Double-blind | Death | 0 | 1 | 0 | 0 | 1 |
| Phase 2: Randomized Double-blind | Received a heart transplant | 0 | 0 | 2 | 0 | 1 |
| Phase 2: Randomized Double-blind | Received left ventricular assist device | 0 | 0 | 1 | 0 | 2 |
| Phase 2: Randomized Double-blind | Received milrinone or dobutamine | 0 | 1 | 0 | 1 | 0 |
| Phase I: Open-label Dose-escalation | Death | 0 | 1 | 0 | 0 | 0 |
| Phase I: Open-label Dose-escalation | Received heart transplant | 1 | 0 | 0 | 0 | 0 |
| Phase I: Open-label Dose-escalation | Received left ventricular assist device | 0 | 0 | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | Phase 1: MYDICAR® Very Low Dose | Total | Phase 2: Placebo | Phase 2: MYDICAR® High Dose | Phase 2: MYDICAR® Mid Dose | Phase 2: MYDICAR® Low Dose | Phase 1: MYDICAR® High Dose | Phase 1: MYDICAR® Low Dose | Phase 1: MYDICAR® Mid Dose |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 53.7 years STANDARD_DEVIATION 7.02 | 60.5 years STANDARD_DEVIATION 11.39 | 61.0 years STANDARD_DEVIATION 11.94 | 56.6 years STANDARD_DEVIATION 13.96 | 63.9 years STANDARD_DEVIATION 8.85 | 60.3 years STANDARD_DEVIATION 10.27 | 58.77 years STANDARD_DEVIATION 19.01 | 55.7 years STANDARD_DEVIATION 4.51 | 48.0 years STANDARD_DEVIATION 8.54 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 6 Participants | 1 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 45 Participants | 13 Participants | 6 Participants | 8 Participants | 8 Participants | 3 Participants | 3 Participants | 1 Participants |
| Sex: Female, Male Female | 0 Participants | 8 Participants | 1 Participants | 3 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 3 Participants | 43 Participants | 13 Participants | 6 Participants | 8 Participants | 7 Participants | 2 Participants | 2 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 3 | 11 / 11 | 11 / 11 | 11 / 12 | 13 / 14 |
| serious Total, serious adverse events | 2 / 3 | 6 / 11 | 5 / 11 | 4 / 12 | 9 / 14 |
Outcome results
Primary
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.
Time frame: Baseline to 6 months
Population: This analysis was performed on the intention to treat population of the Phase 2 period, which included all patients randomized to treatment in the Phase 2 trial.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MYDICAR® Low Dose | Phase 2: Change in 6-minute Walk Test (6MWT) From Baseline to Month 6 | 13.0 meters | Standard Deviation 61.4 |
| MYDICAR® Mid Dose | Phase 2: Change in 6-minute Walk Test (6MWT) From Baseline to Month 6 | -59.5 meters | Standard Deviation 213.64 |
| MYDICAR® High Dose | Phase 2: Change in 6-minute Walk Test (6MWT) From Baseline to Month 6 | 1.0 meters | Standard Deviation 99.69 |
| Placebo | Phase 2: Change in 6-minute Walk Test (6MWT) From Baseline to Month 6 | -86.6 meters | Standard Deviation 164.3 |
Primary
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.
Time frame: Baseline to 6 months
Population: This analysis was performed on the intention to treat population of the Phase 2 period, which included all patients randomized to treatment in the Phase 2 trial.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MYDICAR® Low Dose | Phase 2: Change in Absolute Left Ventricular End Systolic Volume (LVESV) Frm Baseline to Month 6 | 0.4 mL | Standard Deviation 26.16 |
| MYDICAR® Mid Dose | Phase 2: Change in Absolute Left Ventricular End Systolic Volume (LVESV) Frm Baseline to Month 6 | 10.5 mL | Standard Deviation 45.91 |
| MYDICAR® High Dose | Phase 2: Change in Absolute Left Ventricular End Systolic Volume (LVESV) Frm Baseline to Month 6 | -9.6 mL | Standard Deviation 27.55 |
| Placebo | Phase 2: Change in Absolute Left Ventricular End Systolic Volume (LVESV) Frm Baseline to Month 6 | 18.2 mL | Standard Deviation 39.45 |
Primary
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.
Time frame: Baseline to 6 months
Population: This analysis was performed on the intention to treat population of the Phase 2 period, which included all patients randomized to treatment in the Phase 2 trial. NT-proBNP data were not available for 1 patient in the MYDICAR high dose group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MYDICAR® Low Dose | Phase 2: Change in Absolute Levels of N-terminal Prohormone Brain Natriuretic Peptide (NT-proBNP) From Baseline to Month 6 | 694.1 pg/mL | Standard Deviation 1444.94 |
| MYDICAR® Mid Dose | Phase 2: Change in Absolute Levels of N-terminal Prohormone Brain Natriuretic Peptide (NT-proBNP) From Baseline to Month 6 | 2073.1 pg/mL | Standard Deviation 4224.22 |
| MYDICAR® High Dose | Phase 2: Change in Absolute Levels of N-terminal Prohormone Brain Natriuretic Peptide (NT-proBNP) From Baseline to Month 6 | -13.5 pg/mL | Standard Deviation 928.48 |
| Placebo | Phase 2: Change in Absolute Levels of N-terminal Prohormone Brain Natriuretic Peptide (NT-proBNP) From Baseline to Month 6 | 5540.0 pg/mL | — |
Primary
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.
Time frame: Baseline to 6 months
Population: This analysis was performed on the intention to treat population of the Phase 2 period, which included all patients randomized to treatment in the Phase 2 trial.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MYDICAR® Low Dose | Phase 2: Change in Peak Maximum Oxygen Consumption (VO2) From Baseline to Month 6 | -0.73 mL/kg per minute | Standard Deviation 4.88 |
| MYDICAR® Mid Dose | Phase 2: Change in Peak Maximum Oxygen Consumption (VO2) From Baseline to Month 6 | -1.07 mL/kg per minute | Standard Deviation 5.076 |
| MYDICAR® High Dose | Phase 2: Change in Peak Maximum Oxygen Consumption (VO2) From Baseline to Month 6 | -0.43 mL/kg per minute | — |
| Placebo | Phase 2: Change in Peak Maximum Oxygen Consumption (VO2) From Baseline to Month 6 | -2.10 mL/kg per minute | Standard Deviation 4.462 |
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
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.
Time frame: Baseline to 6 months
Population: This analysis was performed on the intention to treat population of the Phase 2 period, which included all patients randomized to treatment in the Phase 2 trial.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MYDICAR® Low Dose | 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 | 0.0 Percentage of blood ejected from the LV | Standard Deviation 1.87 |
| MYDICAR® Mid Dose | 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 | -1.5 Percentage of blood ejected from the LV | Standard Deviation 6.35 |
| MYDICAR® High Dose | 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 | -0.7 Percentage of blood ejected from the LV | Standard Deviation 3.76 |
| Placebo | 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 | -2.1 Percentage of blood ejected from the LV | Standard Deviation 6.9 |
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
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.
Time frame: Baseline to 6 months
Population: This analysis was performed on the intention to treat population of the Phase 2 period, which included all patients randomized to treatment in the Phase 2 trial.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MYDICAR® Low Dose | 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 | Change in NHYA class | -0.8 units on a scale | Standard Deviation 0.71 |
| MYDICAR® Low Dose | 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 | Change in MLWHFQ score | -7.6 units on a scale | Standard Deviation 20.99 |
| MYDICAR® Mid Dose | 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 | Change in MLWHFQ score | 7.9 units on a scale | Standard Deviation 27.28 |
| MYDICAR® Mid Dose | 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 | Change in NHYA class | -0.8 units on a scale | Standard Deviation 0.89 |
| MYDICAR® High Dose | 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 | Change in MLWHFQ score | -10.3 units on a scale | Standard Deviation 12.21 |
| MYDICAR® High Dose | 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 | Change in NHYA class | -0.6 units on a scale | Standard Deviation 0.73 |
| Placebo | 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 | Change in MLWHFQ score | 3.4 units on a scale | Standard Deviation 36 |
| Placebo | 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 | Change in NHYA class | -0.2 units on a scale | Standard Deviation 0.7 |
Primary
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.
Time frame: 12 months
Population: This analysis was performed on the intention to treat population of the Phase 2 period, which included all patients randomized to treatment in the Phase 2 trial.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MYDICAR® Low Dose | Phase 2: Incidence of Treatment-emergent Adverse Events (TEAE) at 12 Months | Any TEAE | 100 percentage of participants |
| MYDICAR® Low Dose | Phase 2: Incidence of Treatment-emergent Adverse Events (TEAE) at 12 Months | TEAEs related to the investigational product (IP) | 50 percentage of participants |
| MYDICAR® Low Dose | Phase 2: Incidence of Treatment-emergent Adverse Events (TEAE) at 12 Months | TEAEs related to administration of the IP | 12.5 percentage of participants |
| MYDICAR® Low Dose | Phase 2: Incidence of Treatment-emergent Adverse Events (TEAE) at 12 Months | Serious TEAEs | 62.5 percentage of participants |
| MYDICAR® Low Dose | Phase 2: Incidence of Treatment-emergent Adverse Events (TEAE) at 12 Months | Serious TEAEs related to the IP | 0 percentage of participants |
| MYDICAR® Low Dose | Phase 2: Incidence of Treatment-emergent Adverse Events (TEAE) at 12 Months | Serious TEAEs related to IP administration | 0 percentage of participants |
| MYDICAR® Mid Dose | Phase 2: Incidence of Treatment-emergent Adverse Events (TEAE) at 12 Months | Serious TEAEs related to IP administration | 0 percentage of participants |
| MYDICAR® Mid Dose | Phase 2: Incidence of Treatment-emergent Adverse Events (TEAE) at 12 Months | Serious TEAEs | 50 percentage of participants |
| MYDICAR® Mid Dose | Phase 2: Incidence of Treatment-emergent Adverse Events (TEAE) at 12 Months | Any TEAE | 100 percentage of participants |
| MYDICAR® Mid Dose | Phase 2: Incidence of Treatment-emergent Adverse Events (TEAE) at 12 Months | TEAEs related to administration of the IP | 25 percentage of participants |
| MYDICAR® Mid Dose | Phase 2: Incidence of Treatment-emergent Adverse Events (TEAE) at 12 Months | TEAEs related to the investigational product (IP) | 12.5 percentage of participants |
| MYDICAR® Mid Dose | Phase 2: Incidence of Treatment-emergent Adverse Events (TEAE) at 12 Months | Serious TEAEs related to the IP | 0 percentage of participants |
| MYDICAR® High Dose | Phase 2: Incidence of Treatment-emergent Adverse Events (TEAE) at 12 Months | TEAEs related to the investigational product (IP) | 11.1 percentage of participants |
| MYDICAR® High Dose | Phase 2: Incidence of Treatment-emergent Adverse Events (TEAE) at 12 Months | TEAEs related to administration of the IP | 11.1 percentage of participants |
| MYDICAR® High Dose | Phase 2: Incidence of Treatment-emergent Adverse Events (TEAE) at 12 Months | Serious TEAEs | 33.3 percentage of participants |
| MYDICAR® High Dose | Phase 2: Incidence of Treatment-emergent Adverse Events (TEAE) at 12 Months | Serious TEAEs related to IP administration | 0 percentage of participants |
| MYDICAR® High Dose | Phase 2: Incidence of Treatment-emergent Adverse Events (TEAE) at 12 Months | Serious TEAEs related to the IP | 0 percentage of participants |
| MYDICAR® High Dose | Phase 2: Incidence of Treatment-emergent Adverse Events (TEAE) at 12 Months | Any TEAE | 88.9 percentage of participants |
| Placebo | Phase 2: Incidence of Treatment-emergent Adverse Events (TEAE) at 12 Months | Serious TEAEs related to the IP | 21.4 percentage of participants |
| Placebo | Phase 2: Incidence of Treatment-emergent Adverse Events (TEAE) at 12 Months | Serious TEAEs related to IP administration | 28.6 percentage of participants |
| Placebo | Phase 2: Incidence of Treatment-emergent Adverse Events (TEAE) at 12 Months | TEAEs related to the investigational product (IP) | 57.1 percentage of participants |
| Placebo | Phase 2: Incidence of Treatment-emergent Adverse Events (TEAE) at 12 Months | Serious TEAEs | 64.3 percentage of participants |
| Placebo | Phase 2: Incidence of Treatment-emergent Adverse Events (TEAE) at 12 Months | Any TEAE | 92.9 percentage of participants |
| Placebo | Phase 2: Incidence of Treatment-emergent Adverse Events (TEAE) at 12 Months | TEAEs related to administration of the IP | 57.1 percentage of participants |
Primary
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.
Time frame: 6 months
Population: This analysis was performed on the intention to treat population of the Phase 2 period, which included all patients randomized to treatment in the Phase 2 trial.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MYDICAR® Low Dose | Phase 2: Length of Cardiovascular-related Hospitalizations at 6 Months | 0.3 days | Standard Deviation 0.46 |
| MYDICAR® Mid Dose | Phase 2: Length of Cardiovascular-related Hospitalizations at 6 Months | 1.3 days | Standard Deviation 2.55 |
| MYDICAR® High Dose | Phase 2: Length of Cardiovascular-related Hospitalizations at 6 Months | 0.2 days | Standard Deviation 0.67 |
| Placebo | Phase 2: Length of Cardiovascular-related Hospitalizations at 6 Months | 2.1 days | Standard Deviation 2.92 |
p-value: 0.078t-test, 2 sided
p-value: 0.515t-test, 2 sided
p-value: 0.098t-test, 2 sided
Other Pre-specified
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.
Time frame: 36 months
Population: Includes all participants enrolled in the Phase 1 or Phase 2 trial. Events occurring after early termination are listed under long-term follow-up. The number of CV deaths in long-term follow-up for the placebo group is greater than the number of Deaths after 12 months, as 2 deaths occurred within 12 months but after early termination.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MYDICAR® Low Dose | Phase 1 and Phase 2: All Subject Deaths Through 36 Months | Cardiovascular deaths in long-term follow-up | 1 participants |
| MYDICAR® Low Dose | Phase 1 and Phase 2: All Subject Deaths Through 36 Months | Deaths after 12 months | 1 participants |
| MYDICAR® Low Dose | Phase 1 and Phase 2: All Subject Deaths Through 36 Months | Deaths within 12 months | 0 participants |
| MYDICAR® Low Dose | Phase 1 and Phase 2: All Subject Deaths Through 36 Months | All deaths during 36 months | 1 participants |
| MYDICAR® Low Dose | Phase 1 and Phase 2: All Subject Deaths Through 36 Months | Cardiovascular deaths on study | 0 participants |
| MYDICAR® Mid Dose | Phase 1 and Phase 2: All Subject Deaths Through 36 Months | Deaths after 12 months | 2 participants |
| MYDICAR® Mid Dose | Phase 1 and Phase 2: All Subject Deaths Through 36 Months | Cardiovascular deaths in long-term follow-up | 2 participants |
| MYDICAR® Mid Dose | Phase 1 and Phase 2: All Subject Deaths Through 36 Months | Deaths within 12 months | 2 participants |
| MYDICAR® Mid Dose | Phase 1 and Phase 2: All Subject Deaths Through 36 Months | All deaths during 36 months | 4 participants |
| MYDICAR® Mid Dose | Phase 1 and Phase 2: All Subject Deaths Through 36 Months | Cardiovascular deaths on study | 2 participants |
| MYDICAR® High Dose | Phase 1 and Phase 2: All Subject Deaths Through 36 Months | Deaths after 12 months | 3 participants |
| MYDICAR® High Dose | Phase 1 and Phase 2: All Subject Deaths Through 36 Months | Cardiovascular deaths in long-term follow-up | 1 participants |
| MYDICAR® High Dose | Phase 1 and Phase 2: All Subject Deaths Through 36 Months | All deaths during 36 months | 3 participants |
| MYDICAR® High Dose | Phase 1 and Phase 2: All Subject Deaths Through 36 Months | Cardiovascular deaths on study | 0 participants |
| MYDICAR® High Dose | Phase 1 and Phase 2: All Subject Deaths Through 36 Months | Deaths within 12 months | 0 participants |
| Placebo | Phase 1 and Phase 2: All Subject Deaths Through 36 Months | Cardiovascular deaths on study | 0 participants |
| Placebo | Phase 1 and Phase 2: All Subject Deaths Through 36 Months | Deaths within 12 months | 0 participants |
| Placebo | Phase 1 and Phase 2: All Subject Deaths Through 36 Months | Deaths after 12 months | 2 participants |
| Placebo | Phase 1 and Phase 2: All Subject Deaths Through 36 Months | Cardiovascular deaths in long-term follow-up | 2 participants |
| Placebo | Phase 1 and Phase 2: All Subject Deaths Through 36 Months | All deaths during 36 months | 2 participants |
| All MYDICAR® | Phase 1 and Phase 2: All Subject Deaths Through 36 Months | Cardiovascular deaths in long-term follow-up | 6 participants |
| All MYDICAR® | Phase 1 and Phase 2: All Subject Deaths Through 36 Months | Deaths within 12 months | 2 participants |
| All MYDICAR® | Phase 1 and Phase 2: All Subject Deaths Through 36 Months | All deaths during 36 months | 10 participants |
| All MYDICAR® | Phase 1 and Phase 2: All Subject Deaths Through 36 Months | Deaths after 12 months | 8 participants |
| All MYDICAR® | Phase 1 and Phase 2: All Subject Deaths Through 36 Months | Cardiovascular deaths on study | 2 participants |
| Placebo | Phase 1 and Phase 2: All Subject Deaths Through 36 Months | Deaths within 12 months | 3 participants |
| Placebo | Phase 1 and Phase 2: All Subject Deaths Through 36 Months | Cardiovascular deaths in long-term follow-up | 4 participants |
| Placebo | Phase 1 and Phase 2: All Subject Deaths Through 36 Months | Deaths after 12 months | 3 participants |
| Placebo | Phase 1 and Phase 2: All Subject Deaths Through 36 Months | All deaths during 36 months | 6 participants |
| Placebo | Phase 1 and Phase 2: All Subject Deaths Through 36 Months | Cardiovascular deaths on study | 1 participants |
Other Pre-specified
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.
Time frame: Baseline to 12 months
Population: This analysis was performed on the intention to treat population of the Phase 2 period, which included all patients randomized to treatment in the Phase 2 trial.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MYDICAR® Low Dose | Phase 2: Change in 6-minute Walk Test (6MWT) From Baseline to Month 12 | -167.9 meters | Standard Deviation 191.02 |
| MYDICAR® Mid Dose | Phase 2: Change in 6-minute Walk Test (6MWT) From Baseline to Month 12 | -115.9 meters | Standard Deviation 226.56 |
| MYDICAR® High Dose | Phase 2: Change in 6-minute Walk Test (6MWT) From Baseline to Month 12 | -23.7 meters | Standard Deviation 151.08 |
| Placebo | Phase 2: Change in 6-minute Walk Test (6MWT) From Baseline to Month 12 | -120.4 meters | Standard Deviation 181.41 |
Other Pre-specified
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.
Time frame: Baseline to 12 months
Population: This analysis was performed on the intention to treat population of the Phase 2 period, which included all patients randomized to treatment in the Phase 2 trial.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MYDICAR® Low Dose | Phase 2: Change in Absolute Left Ventricular End Systolic Volume (LVESV) From Baseline to Month 12 | 40.7 mL | Standard Deviation 59.79 |
| MYDICAR® Mid Dose | Phase 2: Change in Absolute Left Ventricular End Systolic Volume (LVESV) From Baseline to Month 12 | 66.8 mL | Standard Deviation 103.12 |
| MYDICAR® High Dose | Phase 2: Change in Absolute Left Ventricular End Systolic Volume (LVESV) From Baseline to Month 12 | 9.9 mL | Standard Deviation 49.27 |
| Placebo | Phase 2: Change in Absolute Left Ventricular End Systolic Volume (LVESV) From Baseline to Month 12 | 37.7 mL | Standard Deviation 69.09 |
Other Pre-specified
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.
Time frame: Baseline to 12 months
Population: This analysis was performed on the intention to treat population of the Phase 2 period, which included all patients randomized to treatment in the Phase 2 trial. NT-proBNP data were not available for 1 patient in the MYDICAR high dose group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MYDICAR® Low Dose | Phase 2: Change in Absolute Levels of N-terminal Prohormone Brain Natriuretic Peptide (NT-proBNP) From Baseline to Month 12 | 3689.1 pg/mL | Standard Deviation 5109.27 |
| MYDICAR® Mid Dose | Phase 2: Change in Absolute Levels of N-terminal Prohormone Brain Natriuretic Peptide (NT-proBNP) From Baseline to Month 12 | 8440.4 pg/mL | Standard Deviation 11270.44 |
| MYDICAR® High Dose | Phase 2: Change in Absolute Levels of N-terminal Prohormone Brain Natriuretic Peptide (NT-proBNP) From Baseline to Month 12 | 1756.3 pg/mL | Standard Deviation 4331 |
| Placebo | Phase 2: Change in Absolute Levels of N-terminal Prohormone Brain Natriuretic Peptide (NT-proBNP) From Baseline to Month 12 | 11464.3 pg/mL | Standard Deviation 16866.55 |
Other Pre-specified
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.
Time frame: Baseline to 12 months
Population: This analysis was performed on the intention to treat population of the Phase 2 period, which included all patients randomized to treatment in the Phase 2 trial. Peak VO2 data were not available for one patient in the placebo group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MYDICAR® Low Dose | Phase 2: Change in Peak Maximum Oxygen Consumption (VO2) From Baseline to Month 12 | -5.00 mL/kg per minute | Standard Deviation 4.733 |
| MYDICAR® Mid Dose | Phase 2: Change in Peak Maximum Oxygen Consumption (VO2) From Baseline to Month 12 | -3.31 mL/kg per minute | Standard Deviation 5.473 |
| MYDICAR® High Dose | Phase 2: Change in Peak Maximum Oxygen Consumption (VO2) From Baseline to Month 12 | -1.57 mL/kg per minute | Standard Deviation 3.677 |
| Placebo | Phase 2: Change in Peak Maximum Oxygen Consumption (VO2) From Baseline to Month 12 | -2.75 mL/kg per minute | Standard Deviation 5.084 |
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
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.
Time frame: Baseline to 12 months
Population: This analysis was performed on the intention to treat population of the Phase 2 period, which included all patients randomized to treatment in the Phase 2 trial.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MYDICAR® Low Dose | 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 | -6.5 Percentage of blood ejected from the LV | Standard Deviation 7.26 |
| MYDICAR® Mid Dose | 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 | -5.6 Percentage of blood ejected from the LV | Standard Deviation 10.52 |
| MYDICAR® High Dose | 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 | 0.3 Percentage of blood ejected from the LV | Standard Deviation 8.87 |
| Placebo | 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 | -2.5 Percentage of blood ejected from the LV | Standard Deviation 9.96 |
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
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.
Time frame: Baseline to 12 months
Population: This analysis was performed on the intention to treat population, which included all patients randomized to treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MYDICAR® Low Dose | 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 | Change in NHYA class | -0.1 units on a scale | Standard Deviation 0.99 |
| MYDICAR® Low Dose | 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 | Change in MLWHFQ score | 24.4 units on a scale | Standard Deviation 37.3 |
| MYDICAR® Mid Dose | 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 | Change in MLWHFQ score | 22.5 units on a scale | Standard Deviation 32.56 |
| MYDICAR® Mid Dose | 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 | Change in NHYA class | 0.1 units on a scale | Standard Deviation 0.83 |
| MYDICAR® High Dose | 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 | Change in NHYA class | -0.3 units on a scale | Standard Deviation 0.71 |
| MYDICAR® High Dose | 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 | Change in MLWHFQ score | 0.1 units on a scale | Standard Deviation 23.8 |
| Placebo | 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 | Change in NHYA class | 0.1 units on a scale | Standard Deviation 0.73 |
| Placebo | 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 | Change in MLWHFQ score | 14.7 units on a scale | Standard Deviation 34.89 |
Other Pre-specified
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.
Time frame: 12 months
Population: This analysis was performed on the intention to treat population of the Phase 2 period, which included all patients randomized to treatment in the Phase 2 trial.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MYDICAR® Low Dose | Phase 2: Length of Cardiovascular-related Hospitalizations at 12 Months | 10.1 days | Standard Deviation 12.71 |
| MYDICAR® Mid Dose | Phase 2: Length of Cardiovascular-related Hospitalizations at 12 Months | 7.4 days | Standard Deviation 11.8 |
| MYDICAR® High Dose | Phase 2: Length of Cardiovascular-related Hospitalizations at 12 Months | 0.4 days | Standard Deviation 1.33 |
| Placebo | Phase 2: Length of Cardiovascular-related Hospitalizations at 12 Months | 4.5 days | Standard Deviation 5.8 |
Post Hoc
Phase 2: Selected Clinical Outcomes During 12-month Study Period
Incidences of key clinical endpoints as adjudicated by the blinded Clinical Endpoint Committee.
Time frame: 12 months
Population: This analysis was performed on the intention to treat population of the Phase 2 period, which included all patients randomized to treatment in the Phase 2 trial.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MYDICAR® Low Dose | Phase 2: Selected Clinical Outcomes During 12-month Study Period | Fatal cardiovascular event | 12.5 percentage of participants |
| MYDICAR® Low Dose | Phase 2: Selected Clinical Outcomes During 12-month Study Period | Receipt of left ventricular assist device | 0 percentage of participants |
| MYDICAR® Low Dose | Phase 2: Selected Clinical Outcomes During 12-month Study Period | Silent myocardial infarction | 0 percentage of participants |
| MYDICAR® Low Dose | Phase 2: Selected Clinical Outcomes During 12-month Study Period | Worsening heart failure | 50.0 percentage of participants |
| MYDICAR® Low Dose | Phase 2: Selected Clinical Outcomes During 12-month Study Period | Heart transplant | 0 percentage of participants |
| MYDICAR® Low Dose | Phase 2: Selected Clinical Outcomes During 12-month Study Period | Myocardial infarction | 0 percentage of participants |
| MYDICAR® Low Dose | Phase 2: Selected Clinical Outcomes During 12-month Study Period | Heart failure-related hospitalization | 50.0 percentage of participants |
| MYDICAR® Mid Dose | Phase 2: Selected Clinical Outcomes During 12-month Study Period | Receipt of left ventricular assist device | 12.5 percentage of participants |
| MYDICAR® Mid Dose | Phase 2: Selected Clinical Outcomes During 12-month Study Period | Heart failure-related hospitalization | 37.5 percentage of participants |
| MYDICAR® Mid Dose | Phase 2: Selected Clinical Outcomes During 12-month Study Period | Myocardial infarction | 0 percentage of participants |
| MYDICAR® Mid Dose | Phase 2: Selected Clinical Outcomes During 12-month Study Period | Silent myocardial infarction | 0 percentage of participants |
| MYDICAR® Mid Dose | Phase 2: Selected Clinical Outcomes During 12-month Study Period | Heart transplant | 25.0 percentage of participants |
| MYDICAR® Mid Dose | Phase 2: Selected Clinical Outcomes During 12-month Study Period | Worsening heart failure | 37.5 percentage of participants |
| MYDICAR® Mid Dose | Phase 2: Selected Clinical Outcomes During 12-month Study Period | Fatal cardiovascular event | 0 percentage of participants |
| MYDICAR® High Dose | Phase 2: Selected Clinical Outcomes During 12-month Study Period | Heart failure-related hospitalization | 22.2 percentage of participants |
| MYDICAR® High Dose | Phase 2: Selected Clinical Outcomes During 12-month Study Period | Fatal cardiovascular event | 0 percentage of participants |
| MYDICAR® High Dose | Phase 2: Selected Clinical Outcomes During 12-month Study Period | Worsening heart failure | 22.2 percentage of participants |
| MYDICAR® High Dose | Phase 2: Selected Clinical Outcomes During 12-month Study Period | Myocardial infarction | 0 percentage of participants |
| MYDICAR® High Dose | Phase 2: Selected Clinical Outcomes During 12-month Study Period | Silent myocardial infarction | 0 percentage of participants |
| MYDICAR® High Dose | Phase 2: Selected Clinical Outcomes During 12-month Study Period | Receipt of left ventricular assist device | 0 percentage of participants |
| MYDICAR® High Dose | Phase 2: Selected Clinical Outcomes During 12-month Study Period | Heart transplant | 11.1 percentage of participants |
| Placebo | Phase 2: Selected Clinical Outcomes During 12-month Study Period | Myocardial infarction | 14.3 percentage of participants |
| Placebo | Phase 2: Selected Clinical Outcomes During 12-month Study Period | Heart transplant | 7.1 percentage of participants |
| Placebo | Phase 2: Selected Clinical Outcomes During 12-month Study Period | Receipt of left ventricular assist device | 14.3 percentage of participants |
| Placebo | Phase 2: Selected Clinical Outcomes During 12-month Study Period | Worsening heart failure | 50.0 percentage of participants |
| Placebo | Phase 2: Selected Clinical Outcomes During 12-month Study Period | Fatal cardiovascular event | 7.1 percentage of participants |
| Placebo | Phase 2: Selected Clinical Outcomes During 12-month Study Period | Silent myocardial infarction | 0 percentage of participants |
| Placebo | Phase 2: Selected Clinical Outcomes During 12-month Study Period | Heart failure-related hospitalization | 42.9 percentage of participants |