A Study of CLR325 in Chronic Stable Heart Failure Patients.
Condition: Chronic Stable Heart Failure
MeSH terms: Heart Failure
Intervention: CLR325; Placebo
Intervention description: CLR325 Concentrate for solution for infusion; Normal saline
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 26.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Apelin; CLR325; Chronic heart failure

Summary:

      The purpose of this study was to determine the safety and tolerability of CLR325 intravenous
      (i.v.) infusion in patients with stable heart failure to determine if further clinical
      development of the drug in this indication was warranted.
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  Male and female patients >18 years of age

          -  Body weight between 50 kg and 140 kg

          -  Cardiac ejection fraction of ≤ 45% 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 do not require a change
             in their dose of acetylcholinesterase (ACE), angiotensin receptor blocker (ARB),
             β-blocker, mineralocorticoid receptor antagonist, or diuretic for 24 h after
             randomization.

          -  At Baseline, vital signs (systolic and diastolic blood pressure and pulse rate)
             assessment in the supine position after the subject has rested for at least five
             minutes.

        Key Exclusion Criteria:

          -  Impaired renal function as indicated by clinically significant abnormal creatinine
             values (Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m2 calculated
             using the Modification of Diet in Renal Disease Study (MDRD) equation)

          -  History of chronic hepatitis of any non-cardiac etiology

          -  History of any active or clinically significant cardiac tachyarrhythmia (such as
             recurrent atrial fibrillation with rapid ventricular response within the last year)
             and patients with chronic atrial fibrillation with a pulse rate ≤ 100 bpm

          -  Patients who received an i.v. infusion of a cardiac inotrope (e.g., dobutamine or
             milrinone) in the last 24 h prior to randomization

          -  Patients with any significant change in their dose of their ACE, ARB,
             mineralocorticoid receptor antagonist, diuretic, or β-blocker within the last 12 h

          -  Patients with known significant valvular heart diseases indicated by the following:

               -  severe aortic stenosis (aortic valve area < 1.0 cm2 or peak gradient > 50 mm Hg
                  as determined by echocardiography)

               -  severe mitral stenosis

          -  History of acute coronary syndrome within the last 60 days as determined by both
             clinical and enzymatic criteria

          -  For echocardiography-based cohorts only, patients admitted to an inpatient setting for
             acute decompensated heart failure within the last 30 days

          -  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 <
             5 mm Hg on baseline echocardiogram as determined by inferior vena cava criteria.