A Dose-Defining Study of CXL-1020 in Patients With Systolic Heart Failure

Inclusion Criteria: In order to be eligible for randomization, a patient MUST: * Be a male or post menopausal or surgically sterile female requiring inpatient evaluation or treatment and be between 18 and 85 years of age * Not require immediate emergent treatment with conventional parenteral inotropes or vasodilators * Be receiving standard background heart failure therapies as indicated, but not receive an oral dose of a hemodynamically active treatment or diuretic within 3 hours of baseline hemodynamic assessments * Have chronic Systolic HF due to primary/idiopathic dilated cardiomyopathy, coronary artery disease or hypertension * For inclusion in the Non-Invasive Strata B, have a baseline (within 48 hours prior to dosing) left ventricular ejection fraction ≤ 35% estimated from a baseline 2D-Echocardiogram * For inclusion in the Invasive Strata A and C, have baseline hemodynamic values (mean of 3 consecutive CI measurements taken within 1 hours preceding dosing within 10% of one another with a mean CI of less than or equal to (≤) 2.5L/min AND a mean PCWP of greater than 20mmHg * Have an elevated baseline BNP of at least 400pg/ml in all protocol strata * Be capable of understanding the nature of the trial and be willing to participate as documented by written informed consent * Be willing and able to comply with the inpatient and outpatient study protocol requirements for the duration of the study (treatment plus 30 follow up at days) * If a post-menopausal or surgically sterile female, confirmation of sterility status (post-menopausal or surgically sterile for at least 6 months; post-menopausal subjects will require a urine pregnancy test for confirmation) * If a fertile male, must be using 2 approved contraceptive methods (a condom and a spermicidal agent, even if partner(s) is using birth control) for 10 days following participation in the study and further agree to not donate sperm for 10 days after participation in the study * Must have a negative urine test for drugs of abuse and a negative ethanol breath test or blood test at baseline before dosing * Have required local laboratory safety data within protocol required or local laboratory non-exclusionary ranges before dosing * May be receiving ICD, Bi V pacing or rate control pacing at the time of randomization so long as no alteration of settings are anticipated within the day of study drug administration * Exclusion Criteria: In order to be eligible for randomization, a patient MUST NOT: * Have participated in any investigational drug study, SERCa gene therapy or cellular myocardial transplant study within 30 days preceding randomization or have previously received therapy with CXL-1020 * Have received a parenteral or oral dose of diuretics or other hemodynamically active therapy within 3 hours of the baseline hemodynamic assessment * Have received intravenous inotropes, inodilators or vasodilators (amrinone, digoxin, dopamine, dobutamine, enoximone, levosimendan, milrinone, nesiritide, nitroglycerine or nitroprusside) for more than 4 hours and within 12 hours prior to randomization to treatment with study drug * Have a heart rate \<50 or ≥ 90 BPM at baseline prior to randomization * Have a blood pressure \>150 Systolic and/or \>95 diastolic mmHg at baseline prior to randomization * Have a systolic blood pressure of less than 100 mmHg at baseline prior to randomization * Be in atrial fibrillation/flutter at the time of randomization or have a history of recent intermittent A-fib/flutter within the previous week * Have non-sustained VT (HR \> 120 bpm) of 10 beats or more during bedside monitoring prior to randomization or excessive VPB's or complex multifocal ventricular ectopy exceeding 10 beats per minute on a 2 minute rhythm strip taken within 10 minutes prior to randomization * Have a history of successful cardiac resuscitation within the past 2 years. (Inappropriate ICD firings for non lethal arrhythmias are not exclusionary) * Be hospitalized with acute coronary syndrome or acute myocardial infarction during the previous 90 days prior to randomization * Have a history of stroke (CVA) or transient ischemic attack (TIA) within six months prior to randomization * Have a concurrent history of CCS Class III or IV angina * Be a patient whose HF etiology is attributable to either restrictive/obstructive cardiomyopathy, idiopathic hypertrophic cardiomyopathy (as defined by any wall thickness \> 1.8 cm) or uncorrected severe valvular disease * Be receiving concomitant oral or parenteral therapy with any antiarrhythmic drugs other than amiodarone or dronedarone. (only oral therapy is allowed for these agents) * Have unsuitable echocardiographic windows for the Echo assessments (applies only to Strata B) * Have a screening or baseline serum Na \< 130 mEq/l or \> 145 mEq/l; a serum K \< 3.5 mEq/l or \> 5.5 mEq/l; a serum Ca \< 7.5 mg/dl or \> 10.2 mg/dl; or a serum Mg \< 1.6 mEq/l or \> 3.0 mEq/l., or a digoxin level above 1ng/ml * Have a baseline serum creatinine \> 2.5 mg/dl; an ALT or AST \>3 times the upper normal limit; or a hemoglobin \< 10 g/dl * Have taken ethanol within 24 hours (with a positive ethanol breath test or blood test) or a PDE5 inhibitor within 96 hours of study drug administration * Have other clinically significant laboratory or medical conditions that, in the opinion of the Investigator, make the patient unsuitable for evaluation in the study * Be receiving a drug which is expected to possess the potential for a clinically significant pharmacokinetic interaction with CXL-1020, as defined in the investigational drug brochure (IDB). * Be the recipient of a myocardial restraint device or flap * Have an anticipated survival of less than 90 days for any reason Note: Patients receiving cardiac resynchronization therapy for HF are eligible and pacemaker settings have not been changed on this hospitalization and can be left unchanged for the study.