A Study of CLR325 in Chronic Stable Heart Failure Patients.

Inclusion:

- Written informed consent must be obtained before any assessment is performed.

- Able to communicate well with the investigator, to understand and comply with the
requirements of the study.

- Male and female patients >18 years of age.

- Patients must weigh between 50kg and 140 kg to participate in the study.

- Patients with a cardiac ejection fraction of ≤ 45% as assessed within the last 6
months.

- For PA catheter cohorts, patients who are planned to have a clinically indicated
pulmonary artery catheter in place prior to randomization.

- In the opinion of the investigator, heart failure patients who will not require a
change in their dose of ACE, ARB, β-blocker, mineralocorticoid receptor antagonist, or
diuretic for 24 hours after randomization.

- At baseline, vital signs (systolic and diastolic blood pressure and pulse rate) will
be assessed in the sitting position after the subject has rested for at least five
minutes.

Key Exclusion:

- Presence of impaired renal function as indicated by clinically significant abnormal
creatinine values (eGFR < 30 ml/min/1.73m^2 calculated using the MDRD equation).

- Patients with values of AST or ALT >100 U/L measured within the last 3 months before
randomization.

- Chronic infection with Hepatitis B (HBV) or Hepatitis C (HCV). A positive Hepatitis B
surface antigen (HBsAg) test excludes a patient. Patients with a positive Hepatitis C
antibody test should have HCV RNA levels measured. Patients with positive (detectable)
HCV RNA should be excluded.

- Patients with a history of chronic hepatitis of any non-cardiac etiology.

- History of any active, clinically significant cardiac tachyarrhythmia, such as
recurrent atrial fibrillation with rapid ventricular response within the last year.
Anticoagulation for patients with atrial fibrillation should be managed per usual
clinical practice for patients undergoing right heart catheterization.

- For Echocardiography-based cohort only, patients admitted to an inpatient setting for
acute decompensated heart failure within the last 30 days.

- Patients who have received an intravenous infusion of a cardiac inotrope
(e.g.,dobutamine or milrinone) in the last 24 hours prior to randomization.

- For PA catheter cohorts, patients with a pulmonary capillary wedge pressure of <10 mm
Hg at baseline. For echocardiographic cohorts, patients with a lateral E/E' ratio of
<7 on their baseline echocardiogram. For patients in whom a lateral E/E' ratio cannot
be determined (e.g., patients in atrial fibrillation), a central venous pressure of
<5mm Hg on baseline echocardiogram as determined by inferior vena cava criteria.

- Patients with any significant change in their dose of their ACE, ARB,
mineralocorticoid receptor antagonist, diuretic or β-blocker within the last 12 hours.

Patients with minor changes in their heart failure regimen may be eligible if deemed
clinically stable by both the investigator and sponsor.

- Patients with known significant valvular heart disease, as indicated by the following:

- Severe aortic stenosis (Aortic Valve Area < 1.0 cm^2 or peak gradient > 50 mmHg
as determined by echocardiography)

- Severe mitral stenosis

- Patients with history of acute coronary syndrome within the last 60 days as determined
by both clinical and enzymatic criteria.