Brief 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)
Brief Title
Pharmacokinetics & Safety of Serelaxin on Top of Standard of Care Therapy in Pediatric Patients With Acute Heart Failure
Detailed 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
Completion Date
Completion Date Type
Actual
Conditions
Acute Heart Failure
Eligibility Criteria
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
* 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
Inclusion Criteria
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.
* 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.
Gender
All
Gender Based
false
Keywords
Acute heart failure
RELAX-AHF-PEDIATRIC PK
AHF
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
17 Years
NCT Id
NCT02151383
Org Class
Industry
Org Full Name
Novartis
Org Study Id
CRLX030A2208
Overall Status
Terminated
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
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
Primary Outcomes
Outcome Description
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.
Outcome Measure
Number of Patients With Treatment Emergent Adverse Events, Serious Adverse Events and Death
Outcome Time Frame
through 28 days + 30 days SAE follow up after completion or discontinuation from the study
Outcome Description
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.
Outcome Measure
Pharmacokinetic Concentration for Low Dose 3-10-30 ug/kg/Day
Outcome Time Frame
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
Outcome Description
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.
Outcome Measure
Pharmacokinetic Concentration for High Dose (10-30-100 ug/kg/Day)
Outcome Time Frame
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 Ids
Secondary Id
2013-002847-28
Secondary Outcomes
Outcome Description
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.
Outcome Time Frame
baseline, prior to each dose escalation, and at 24 hr. post end of infusion
Outcome Measure
Change From Baseline in Mean Left Arterial Pressure for Low Dose (3-10-30 ug/kg/Day)
Outcome Description
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.
Outcome Time Frame
baseline, prior to each dose escalation, and at 24 hr. post end of infusion
Outcome Measure
Change From Baseline in Mean Left Arterial Pressure for High Dose (10 -30-100 ug/kg/Day)
Outcome Description
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
Outcome Time Frame
Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day3: 24 hours post infusion
Outcome Measure
Change From Baseline in Mean Pulmonary Artery Pressure (PAP- Systolic and Diastolic) for Low Dose (3-10-30 ug/kg/Day)
Outcome Description
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
Outcome Time Frame
Day 1: hour 0 and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusion
Outcome Measure
Change From Baseline in Mean Pulmonary Artery Pressure (PAP- Systolic and Diastolic) for High Dose (10-30-100 ug/kg/Day)
Outcome Description
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
Outcome Time Frame
Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusion
Outcome Measure
Change From Baseline in Mean Central Venous Pressure for Low Dose (3-10-30 ug/kg/Day)
Outcome Description
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
Outcome Time Frame
Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusion
Outcome Measure
Change From Baseline in Mean Central Venous Pressure for High Dose (10-30-100 ug/kg/Day)
Outcome Description
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
Outcome Time Frame
Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusion
Outcome Measure
Baseline and Change From Baseline in Mean Central Venous Pressure and Arterial Oxygen Saturation for Low Dose (3-10-30 ug/kg/Day)
Outcome Description
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
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
Outcome Time Frame
Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusion
Outcome Measure
Baseline and Change From Baseline in Mean Central Venous Pressure and Arterial Oxygen Saturation for High Dose (10-30-100 ug/kg/Day)
Outcome Description
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
Outcome Time Frame
Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusion
Outcome Measure
Baseline and Change From Baseline in Mean Urine Output for Low Dose (3-10-30 ug/kg/Day)
Outcome Description
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
Outcome Time Frame
Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusion
Outcome Measure
Baseline and Change From Baseline in Mean Urine Output for High Dose (10-30-100 ug/kg/Day)
Outcome Description
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
Outcome Time Frame
Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusion
Outcome Measure
Baseline and Change From Baseline in Mean Blood Lactate Levels (Arterial Blood) for Low Dose (3-10-30 ug/kg/Day)
Outcome Description
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
Outcome Time Frame
Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusion
Outcome Measure
Baseline and Change From Baseline in Mean Blood Lactate Levels (Central Venous Blood) for Low Dose (3-10-30 ug/kg/Day)
Outcome Description
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
Outcome Time Frame
Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusion
Outcome Measure
Baseline and Change From Baseline in Mean Blood Lactate Levels (Arterial Blood) for High Dose (10-30-100 ug/kg/Day)
Outcome Description
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
Outcome Time Frame
Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusion
Outcome Measure
Baseline and Change From Baseline in Mean Blood Lactate Levels (Central Venous Blood) for High Dose (10-30-100 ug/kg/Day)
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Child
Maximum Age Number (converted to Years and rounded down)
17
Minimum Age Number (converted to Years and rounded down)
0
Investigators
Investigator Type
Principal Investigator
Investigator Name
Daphne Hsu
Investigator Email
dhsu@montefiore.org
Investigator Phone
718-741-2538
MeSH Terms
SERELAXIN PROTEIN, HUMAN