A Study To InvestigateThe Safety, Tolerability And Efficacy Of Nebulised Curosurf® In Preterm Neonates With Respiratory Distress Syndrome (RDS)

Study Overview
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Brief Summary
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The present study will mainly aim at investigating the safety, tolerability and efficacy of different escalating single doses administration of nebulised Curosurf®, in preterm neonates with RDS (Respiratory Distress Syndrome) during nCPAP.

Detailed Description
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The study will be conducted in spontaneously breathing preterm neonates with mild to moderate RDS and will consist of two parts: Part I, with the objective to assess the safety and tolerability of single ascending doses of nebulised Curosurf® ; Part II, with the objective to compare the efficacy of nebulised Curosurf®, administered at two selected doses from part I, during nCPAP, versus nCPAP alone in terms of incidence of respiratory failure in the first 72 hours of life.

Official Title
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A Randomized, Open, Multinational, Multicentre,2-Part Study In Spontaneously Breathing Preterm Neonates With Mild To Moderate Respiratory Distress Syndrome (RDS) To Investigate The Safety, Tolerability And Efficacy Of Inhaled Nebulised Poractant Alfa (Porcine Surfactant, Curosurf®) In Comparison With Nasal Continuous Positive Airway Pressure (nCPAP) Alone

Conditions
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Neonatal Respiratory Distress Syndrome

Intervention / Treatment
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* Drug: nCPAP (nasal Continuous Positive Airway Pressure) + Nebulised Curosurf® (Part I)
* Drug: nCPAP (nasal Continuous Positive Airway Pressure) + Nebulised Curosurf® (Part II)
* Other: nCPAP (nasal Continuous Positive Airway Pressure) alone (Part I)
* Other: nCPAP (nasal Continuous Positive Airway Pressure) alone (Part II)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent obtained by parents/legal representative (according to local regulation) prior to or after birth Inborn neonates from 28+0 to 32+6 weeks of gestational age (GA), spontaneously breathing and stabilised on nCPAP Clinical course consistent with RDS. Receiving CPAP pressure 5-8 centimeter of water (cm H2O) and fraction of inspired oxygen (FiO2) between 0.25 and 0.40 to maintain saturation of peripheral oxygen (SpO2) between 88% and 95% for at least 30 minutes. Randomization should occur between 60 minutes and 12 hours after birth. Exclusion Criteria: Early need for endotracheal intubation for cardiopulmonary resuscitation in delivery room or within 1 hour from birth because of severe RDS Respiratory Distress not secondary to surfactant deficiency Use of surfactant prior to study entry and need for endotracheal administration of any other treatment. Major congenital anomalies. Evidence of severe birth asphyxia Mothers with prolonged rupture of the membranes Presence of air leaks. Presence of IVH (intraventricular hemorrhage ) ≥ III. Hypotension or evidence of hemodynamic instability. Any condition that, in the opinion of the Investigator, would place the neonate at undue risk. Participation in another clinical trial

Ages Eligible for Study
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Minimum Age: 28 Weeks
Maximum Age: 32 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Part I is an ascending dose scheme of IMP versus nCPAP alone. Part II is a parallel group with 2 doses of IMP versus nCPAP alone. In part II, one additional dose may be administered between 3 and 12 hours after the start of the first dose.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: nCPAP+ Nebulised Curosurf®<br>Curosurf® administered through nebulization | Drug: nCPAP (nasal Continuous Positive Airway Pressure) + Nebulised Curosurf® (Part I)<br>* Single ascending doses of Curosurf® administered through nebulisation to neonates receiving nCPAP (Part I)<br>Drug: nCPAP (nasal Continuous Positive Airway Pressure) + Nebulised Curosurf® (Part II)<br>* Two doses of Curosurf® administered through nebulisation to neonates receiving nCPAP (Part II)<br>|
| Other: nCPAP alone (control)<br>Standard of care, respiratory support used also during experimental arms | Other: nCPAP (nasal Continuous Positive Airway Pressure) alone (Part I)<br>* Nasal continuous positive airway pressure alone<br>Other: nCPAP (nasal Continuous Positive Airway Pressure) alone (Part II)<br>* nasal continuous positive airway pressure alone<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of neonates with respiratory failure | Respiratory failure defined as: need for endotracheal surfactant administration and/or mechanical ventilation | in the first 72 hours of life | 
| Adverse Events | Any untoward medical occurrence in a clinical trial neonate administered a medicinal product and which does not necessarily have a casual relationship with the treatment | discharge or 36 weeks post menstrual age (PMA), whichever comes first | 
| Adverse Drug Reactions | Any untoward and unintended responses to an investigational product related to any dose administered | discharge or 36 weeks post menstrual age (PMA), whichever comes first | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RDS