Pharmacokinetics & Safety of Serelaxin on Top of Standard of Care Therapy in Pediatric Patients With Acute Heart Failure (RELAX-PEDS-PK)

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

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)

Study Overview

• Status: Terminated
• Conditions: Acute Heart Failure
• Intervention / Treatment: Drug: Serelaxin

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

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 13353
    • Novartis Investigative Site
  • Freiburg, Germany, 79106
    • Novartis Investigative Site
  • Muenchen, Germany, 80636
    • Novartis Investigative Site
• Switzerland
  • Genève, Switzerland, 1211
    • Novartis Investigative Site
• United Kingdom
  • London, United Kingdom, WC1N 1EH
    • Novartis Investigative Site
• United States
  • Colorado
    • Denver, Colorado, United States, 80218
      • Novartis Investigative Site
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Novartis Investigative Site
  • New York
    • Bronx, New York, United States, 10467
      • Novartis Investigative Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Novartis Investigative Site
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 17 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Serelaxin; Serelaxin was administered intravenously on top of standard therapy for acute heart failure, for a total of 48 hours.	Drug: Serelaxin; Serelaxin was administered intravenously for up to 48 hours.; Other Names: RLX030

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 5, 2014
• Primary Completion (ACTUAL): April 3, 2017
• Study Completion (ACTUAL): April 3, 2017

Study Registration Dates

• First Submitted: May 28, 2014
• First Submitted That Met QC Criteria: May 28, 2014
• First Posted (ESTIMATE): May 30, 2014

Study Record Updates

• Last Update Posted (ACTUAL): June 25, 2019
• Last Update Submitted That Met QC Criteria: June 1, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: Acute heart failure; AHF; RELAX-AHF-PEDIATRIC PK
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: CRLX030A2208; 2013-002847-28 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No