Clinical trial NCT02696967: A Study of CLR325 in Chronic Stable Heart Failure Patients.
Official title: A Randomized, Subject and Investigator-blind, Placebo-controlled Study of CLR325 in Chronic Stable Heart Failure Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Stable Heart Failure
Keywords: Apelin
CLR325
Chronic heart failure
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2016-03-02
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Number of Patients With Adverse Events, Serious Adverse Events and Death
timeFrame: Day 1 to 28
Secondary outcomes:
measure: Pharmacokinetic of CLR325 and CQJ295: Area Under the Plasma Concentration-time Curve From Time Zero to 18 Hours (AUC0-18hr)
timeFrame: 0, 0.5, 3, 5, 8, 10, 12, and 18 hours post start of CLR325 infusion on Day 1
measure: Pharmacokinetic of CLR325 and CQJ295: Area Under the Plasma Concentration-time Curve From From Time Zero to 28 Hours (AUC0-28hrs)
timeFrame: 0, 0.5, 3, 5, 8, 10, 12, 18, 20, 24, and 28 hours post start of CLR325 infusion on Day 1
measure: Pharmacokinetic of CLR325 and CQJ295: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf)
timeFrame: 0, 0.5, 3, 5, 8, 10, 12, 18, 20, 24, and 28 hours post start of CLR325 infusion on Day 1
measure: Pharmacokinetic of CLR325 and CQJ295: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast)
timeFrame: 0, 0.5, 3, 5, 8, 10, 12, 18, 20, 24, and 28 hours post start of CLR325 infusion on Day 1
measure: Pharmacokinetic of CLR325: Clearance From Plasma (CL) Following Drug Administration
timeFrame: 0, 0.5, 3, 5, 8, 10, 12, 18, 20, 24, and 28 hours post start of CLR325 infusion on Day 1
measure: Pharmacokinetic of CLR325 and CQJ295: Observed Maximum Plasma Concentration Following Drug Administration at Steady State (Cmax,ss)
timeFrame: 0, 0.5, 3, 5, 8, 10, 12, 18, 20, 24, and 28 hours post start of CLR325 infusion on Day 1
measure: Pharmacokinetic of CLR325 and CQJ295: Terminal Elimination Half-life (T1/2)
timeFrame: 18, 20, 24, and 28 hours post start of CLR325 infusion on Day 1
measure: Pharmacokinetic of CLR325 and CQJ295: Time to Reach the Maximum Concentration After Drug Administration (TMax)
timeFrame: 0, 0.5, 3, 5, 8, 10, 12, 18, 20, 24, and 28 hours post start of CLR325 infusion on Day 1
measure: Pharmacokinetic of CLR325: Volume of Distribution at Steady State Following Intravenous Administration (Vss)
timeFrame: 0, 0.5, 3, 5, 8, 10, 12, 18, 20, 24, and 28 hours post start of CLR325 infusion on Day 1
measure: Pharmacokinetic of CLR325 and CQJ295: Amount of Drug (or Defined Metabolite) Excreted Into the Urine From Time (Ae 0-28 Hours)
timeFrame: 0-28 hours on Day 1
measure: Pharmacokinetic of CLR325 and CQJ295: Renal Clearance From Plasma (CLr) Following Drug Administration
timeFrame: 0-28 hours on Day 1
measure: Number of Patients With Increase in Anti-CLR325 and Anti-apelin Antibodies in Serum
timeFrame: Baseline (BL), Day 10 (D10) and Day 28 (D28)
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Novartis Investigative Site
state: Illinois
city: Saint Louis
country: United States
facility: Novartis Investigative Site
state: Missouri
city: Cleveland
country: United States
facility: Novartis Investigative Site
state: Ohio
city: Philadelphia
country: United States
facility: Novartis Investigative Site
state: Pennsylvania
city: Houston
country: United States
facility: Novartis Investigative Site
state: Texas
city: Tacoma
country: United States
facility: Novartis Investigative Site
state: Washington
city: Aalst
country: Belgium
facility: Novartis Investigative Site
city: Regensburg
country: Germany
facility: Novartis Investigative Site
state: Bavaria
city: Greifswald
country: Germany
facility: Novartis Investigative Site
city: Amsterdam
country: Netherlands
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: