A Study of CLR325 in Chronic Stable Heart Failure Patients.

Novartis

Status and phase: Completed; Phase 2

Conditions: Chronic Stable Heart Failure

Treatments: Drug: CLR325; Other: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02696967

2016-001387-12 (EudraCT Number)

CCLR325X2202

Details and patient eligibility

About

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.

Enrollment: 26 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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26 participants in 2 patient groups, including a placebo group

CLR325

Experimental group

Description:

Patients were assigned to one of the 2 treatment arms in fixed randomization ratio. Patients randomized to this arm received single dose of CLR325 (i.v.) in double blind manner.

Treatment:

Drug: CLR325

Placebo

Placebo Comparator group

Description:

Patients were assigned to one of the 2 treatment arms in fixed randomization ratio. Patients randomized to this arm received single dose of placebo (i.v.) in double blind manner.

Treatment:

Other: Placebo