Pharmacokinetics & Safety of Serelaxin on Top of Standard of Care Therapy in Pediatric Patients With Acute Heart Failure

Acute Heart Failure Clinical Trial

— RELAX-PEDS-PK  

Official title:

Multicenter, Open-label, Dose Escalation Study to Evaluate Safety, Tolerability and Pharmacokinetics of RLX030 in Addition to Standard of Care in Pediatric Patients From Birth to <18 Years of Age, Hospitalized With Acute Heart Failure

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02151383
• Other study ID #: CRLX030A2208
• Secondary ID: 2013-002847-28
• Status: Terminated
• Phase: Phase 2
• Start date: September 5, 2014
• Est. completion date: April 3, 2017

Study information

• Verified date: May 2019
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the study was to evaluate the safety, tolerability and pharmacokinetics of an intravenous infusion of serelaxin on top of standard of care therapy, in pediatric patients with acute heart failure (AHF)

Description:

The study was terminated early and the pediatric development of serelaxin in the treatment of acute heart failure (AHF) discontinued, following the results of the phase III study RELAX-AHF-2 (CRLX030A2301/NCT01870778) study in adult patients with AHF. Whilst no new safety concerns associated with serelaxin were observed, the study in adults did not meet either of its primary endpoints

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 12
• Est. completion date: April 3, 2017
• Est. primary completion date: April 3, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 17 Years

Eligibility

Key Inclusion criteria:

• Body weight =2.5 kg to =120 kg

• Hospitalized in an intensive care unit or step-down unit with the following:

• - Signs and symptoms of acute heart failure of any etiology

• - Stable dose of vasoactive and/or inotropic drugs

• - For non-surgical patients echocardiographic evidence of reduced ventricular function (ejection fraction <50% or fractional shortening <28%)

• Systolic blood pressure (SBP) =25th percentile SBP for age and gender.

Key Exclusion criteria:

• Moderate to severe left ventricular outflow tract, mitral stenosis, or aortic arch obstruction

• Single ventricle physiology

• Fixed pulmonary hypertension

• Blood lactate levels >5 mmol/L at screening

• Birth < 36 weeks post-conceptual age (for patients <1year old)

• Confirmed or clinically suspected systemic infection or severe localized infection

• Dyspnea or acute lung injury primarily due to non-cardiac causes

• Patients with severe renal impairment, those known to have significant renal disease and those having renal replacement therapy

• High use of inotropic and/or vasoactive agents at screening

• Electrocardiographic abnormalities

• Solid organ transplant recipient within 1 year of transplantation or one who presents with severe organ rejection

Related Conditions & MeSH terms

• Acute Heart Failure
• Heart Failure

Intervention

Drug:
• Serelaxin
Serelaxin was administered intravenously for up to 48 hours.

Locations

Country	Name	City	State
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Freiburg
Germany	Novartis Investigative Site	Muenchen
Switzerland	Novartis Investigative Site	Genève
United Kingdom	Novartis Investigative Site	London
United States	Novartis Investigative Site	Bronx	New York
United States	Novartis Investigative Site	Charleston	South Carolina
United States	Novartis Investigative Site	Denver	Colorado
United States	Novartis Investigative Site	Philadelphia	Pennsylvania
United States	Novartis Investigative Site	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Germany,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Patients With Treatment Emergent Adverse Events, Serious Adverse Events and Death	Number of patients with treatment emergent adverse events (including confirmed systolic blood pressure decreases and worsening heart failure), serious adverse events and death were reported.	through 28 days + 30 days SAE follow up after completion or discontinuation from the study
Primary	Pharmacokinetic Concentration for Low Dose 3-10-30 ug/kg/Day	Pharmacokinetic (PK) concentration was presented as the surrogate for PK parameters, the original primary endpoint, due to the unavailability of the PK parameters Css and CL. Serelaxin concentration was determined in serum by a validated Enzyme Linked ImmunoSorbent Assay (ELISA) based upon the commercially available kit from R&D Systems (Catalogue No. DRL200). The ELISA method used a monoclonal antibody specific for human H2 relaxin as the capture reagent and an enzyme-linked polyclonal antibody specific for human.	at 0, 2, 16, 22, 32, 40, 48 hr. during the infusion, at 0.5, 4, 8 hours post infusion or study drug discontinuation, and on day 28
Primary	Pharmacokinetic Concentration for High Dose (10-30-100 ug/kg/Day)	Pharmacokinetic (PK) concentration was presented as the surrogate for PK parameters, the original primary endpoint, due to the unavailability of the PK parameters Css and CL. Serelaxin concentration was determined in serum by a validated Enzyme Linked ImmunoSorbent Assay (ELISA) based upon the commercially available kit from R&D Systems (Catalogue No. DRL200). The ELISA method used a monoclonal antibody specific for human H2 relaxin as the capture reagent and an enzyme-linked polyclonal antibody specific for human.	at 0, 2, 16, 22, 32, 40, 48 hr. during the infusion, at 0.5, 4, 8 hours post infusion or study drug discontinuation, and on day 28
Secondary	Change From Baseline in Mean Left Arterial Pressure for Low Dose (3-10-30 ug/kg/Day)	The evaluations, as available, were done at baseline, prior to each dose escalation and at approximately 24 hours after the end of the infusion. Hemodynamic effects were also assessed for safety at additional time points during the study.	baseline, prior to each dose escalation, and at 24 hr. post end of infusion
Secondary	Change From Baseline in Mean Left Arterial Pressure for High Dose (10 -30-100 ug/kg/Day)	The evaluations, as available, were done at baseline, prior to each dose escalation and at approximately 24 hours after the end of the infusion. Hemodynamic effects were also assessed for safety at additional time points during the study.	baseline, prior to each dose escalation, and at 24 hr. post end of infusion
Secondary	Change From Baseline in Mean Pulmonary Artery Pressure (PAP- Systolic and Diastolic) for Low Dose (3-10-30 ug/kg/Day)	The evaluations, as available, were done at baseline, prior to each dose escalation and at approximately 24 hours after the end of the infusion. Hemodynamic effects were also assessed for safety at additional time points during the study. Absolute values are presented at baseline; change from baseline values are presented at post-baseline time points	Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day3: 24 hours post infusion
Secondary	Change From Baseline in Mean Pulmonary Artery Pressure (PAP- Systolic and Diastolic) for High Dose (10-30-100 ug/kg/Day)	The evaluations, as available, were done at baseline, prior to each dose escalation and at approximately 24 hours after the end of the infusion. Hemodynamic effects were also assessed for safety at additional time points during the study. Absolute values are presented at baseline; change from baseline values are presented at post-baseline time points	Day 1: hour 0 and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusion
Secondary	Change From Baseline in Mean Central Venous Pressure for Low Dose (3-10-30 ug/kg/Day)	The evaluations, as available, were done at baseline, prior to each dose escalation and at approximately 24 hours after the end of the infusion. Hemodynamic effects were also assessed for safety at additional time points during the study. Absolute values are presented at baseline; change from baseline values are presented at post-baseline time points	Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusion
Secondary	Change From Baseline in Mean Central Venous Pressure for High Dose (10-30-100 ug/kg/Day)	The evaluations, as available, were done at baseline, prior to each dose escalation and at approximately 24 hours after the end of the infusion. Hemodynamic effects were also assessed for safety at additional time points during the study. Absolute values are presented at baseline; change from baseline values are presented at post-baseline time points	Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusion
Secondary	Baseline and Change From Baseline in Mean Central Venous Pressure and Arterial Oxygen Saturation for Low Dose (3-10-30 ug/kg/Day)	This analysis includes central venous and arterial oxygen saturation measurement, yielding a calculation of the arterio-venous oxygen extraction, where available at each time point. If no arterial access was available, then arterial oxygen saturation measurement data were obtained using a pulse oximeter. The evaluations, as available, were done at baseline, prior to each dose escalation and at approximately 24 hours after the end of the infusion. Hemodynamic effects were also assessed for safety at additional time points during the study. Absolute values are presented at baseline; change from baseline values are presented at post-baseline time points	Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusion
Secondary	Baseline and Change From Baseline in Mean Central Venous Pressure and Arterial Oxygen Saturation for High Dose (10-30-100 ug/kg/Day)	This analysis includes central venous and arterial oxygen saturation measurement, yielding a calculation of the arterio-venous oxygen extraction, where available at each time point. If no arterial access was available, then arterial oxygen saturation measurement data were obtained using a pulse oximeter.; The evaluations, as available, were done at baseline, prior to each dose escalation and at approximately 24 hours after the end of the infusion. Hemodynamic effects were also assessed for safety at additional time points during the study. Absolute values are presented at baseline; change from baseline values are presented at post-baseline time points	Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusion
Secondary	Baseline and Change From Baseline in Mean Urine Output for Low Dose (3-10-30 ug/kg/Day)	The evaluations, as available, were done at baseline, prior to each dose escalation and at approximately 24 hours after the end of the infusion. Hemodynamic effects were also assessed for safety at additional time points during the study. Absolute values are presented at baseline; change from baseline values are presented at post-baseline time points	Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusion
Secondary	Baseline and Change From Baseline in Mean Urine Output for High Dose (10-30-100 ug/kg/Day)	The evaluations, as available, were done at baseline, prior to each dose escalation and at approximately 24 hours after the end of the infusion. Hemodynamic effects were also assessed for safety at additional time points during the study. Absolute values are presented at baseline; change from baseline values are presented at post-baseline time points	Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusion
Secondary	Baseline and Change From Baseline in Mean Blood Lactate Levels (Arterial Blood) for Low Dose (3-10-30 ug/kg/Day)	The evaluations, as available, were done at baseline, prior to each dose escalation and at approximately 24 hours after the end of the infusion. Hemodynamic effects were also assessed for safety at additional time points during the study. Absolute values are presented at baseline; change from baseline values are presented at post-baseline time points	Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusion
Secondary	Baseline and Change From Baseline in Mean Blood Lactate Levels (Central Venous Blood) for Low Dose (3-10-30 ug/kg/Day)	The evaluations, as available, were done at baseline, prior to each dose escalation and at approximately 24 hours after the end of the infusion. Hemodynamic effects were also assessed for safety at additional time points during the study. Absolute values are presented at baseline; change from baseline values are presented at post-baseline time points	Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusion
Secondary	Baseline and Change From Baseline in Mean Blood Lactate Levels (Arterial Blood) for High Dose (10-30-100 ug/kg/Day)	The evaluations, as available, were done at baseline, prior to each dose escalation and at approximately 24 hours after the end of the infusion. Hemodynamic effects were also assessed for safety at additional time points during the study. Absolute values are presented at baseline; change from baseline values are presented at post-baseline time points	Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusion
Secondary	Baseline and Change From Baseline in Mean Blood Lactate Levels (Central Venous Blood) for High Dose (10-30-100 ug/kg/Day)	The evaluations, as available, were done at baseline, prior to each dose escalation and at approximately 24 hours after the end of the infusion. Hemodynamic effects were also assessed for safety at additional time points during the study. Absolute values are presented at baseline; change from baseline values are presented at post-baseline time points	Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusion