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

NCT02151383 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: CRLX030A22082013-002847-28
• Study Type: interventional
• Target: 12
• Locations: 4 countries
• Sites: 10

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)

Conditions

Acute Heart Failure

Keywords

Acute heart failure; RELAX-AHF-PEDIATRIC PK; AHF

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (14)

• Change From Baseline in Mean Left Arterial Pressure for Low Dose (3-10-30 ug/kg/Day)

  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)

  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)

  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)

  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)

  Day 1: hour 0 (Baseline) and 16, Day 2: hour 32 and 48, Day 3: 24 hours post infusion

Study Arms (1)

Serelaxin

EXPERIMENTAL

Serelaxin was administered intravenously on top of standard therapy for acute heart failure, for a total of 48 hours.

Drug: Serelaxin

Interventions

Serelaxin DRUG

Serelaxin was administered intravenously for up to 48 hours.

Also known as: RLX030

Serelaxin

Eligibility Criteria

• Age: Up to 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (10)

Novartis Investigative Site

Denver, Colorado, 80218, United States

Location

Novartis Investigative Site

St Louis, Missouri, 63110, United States

Location

Novartis Investigative Site

The Bronx, New York, 10467, United States

Location

Novartis Investigative Site

Philadelphia, Pennsylvania, 19104, United States

Location

Novartis Investigative Site

Charleston, South Carolina, 29425, United States

Location

Novartis Investigative Site

Berlin, 13353, Germany

Location

Novartis Investigative Site

Freiburg im Breisgau, 79106, Germany

Location

Novartis Investigative Site

München, 80636, Germany

Location

Novartis Investigative Site

Geneva, 1211, Switzerland

Location

Novartis Investigative Site

London, WC1N 1EH, United Kingdom

Location

MeSH Terms

Interventions

serelaxin protein, human

Limitations and Caveats

Due to the early termination of the study, the planned analyses were not performed as the limited set of data would preclude meaningful interpretation.

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2014
• First Posted: May 30, 2014
• Study Start: September 5, 2014
• Primary Completion: April 3, 2017
• Study Completion: April 3, 2017
• Last Updated: June 25, 2019
• Results First Posted: June 25, 2019

Record last verified: 2019-05

Locations

US (5); CH (1); DE (3); GB (1)