A Double Blind, Randomized, Controlled Study to Evaluate CHF 5633 (Synthetic Surfactant) and Poractant Alfa in Neonates With Respiratory Distress Syndrome (RDS) (POC)

Study Overview
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Brief Summary
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A multicenter, double blind, randomized, single dose, active-controlled study to investigate the efficacy and safety of synthetic surfactant (CHF 5633) in comparison to porcine surfactant (Poractant alfa, Curosurf ®) in the treatment of preterm neonates with respiratory distress syndrome. Main objectives of this study are to investigate the short term efficacy profile of CHF 5633 vs. porcine surfactant (Poractant Alfa, Curosurf®) in terms of reduced oxygen requirement and ventilatory support and to evaluate the mid-term efficacy profile in terms of reduced incidence of bronchopulmonary dysplasia (BPD) and mortality/BPD rate at 36 weeks post menstrual age (PMA), mortality rate at 28 days and 36 weeks PMA, RDS-associated mortality through 14 days of age and other major co-morbidities of prematurity. Inclusion criteria are: Written parental informed consent, inborn preterm neonates of either sex with a gestational age of 24+0 weeks up to 29+6 weeks, clinical course consistent with RDS, requirement of endotracheal surfactant administration within 24 hours from birth, fraction of inspired oxygen (FiO2) ≥0.30 for babies 24+0 to 26+6 weeks and FiO2 ≥0.35 for babies 27+0 to 29+6 weeks to maintain arterial oxygen saturation by pulse oximetry (SpO2) between 88-95%.

Official Title
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A DOUBLE BLIND, RANDOMIZED, CONTROLLED STUDY TO INVESTIGATE THE EFFICACY AND SAFETY OF SYNTHETIC SURFACTANT (CHF 5633) IN COMPARISON TO PORCINE SURFACTANT (PORACTANT ALFA, CUROSURF®) IN THE TREATMENT OF PRETERM NEONATES WITH RESPIRATORY DISTRESS SYNDROME

Conditions
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Respiratory Distress Syndrome, Newborn

Intervention / Treatment
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* Drug: CHF5633
* Drug: Poractant alfa


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 any study-related procedures Inborn preterm neonates of either sex with a gestational age of 24+0 weeks up to 29+6 weeks Clinical course consistent with RDS Requirement of endotracheal surfactant administration within 24 hours from birth Fraction of inspired oxygen (FiO2) ≥0.30 for babies 24+0 to 26+6 weeks and FiO2 ≥0.35 for babies 27+0 to 29+6 weeks to maintain SpO2 between 88-95% Exclusion Criteria: Use of surfactant prior to study entry and need for intratracheal administration of any other treatment (e.g. nitric oxide) Known genetic or chromosomal disorders, major congenital anomalies (cardiac malformations, myelomeningocele etc) Maternal drug abuse (heroin, methadone, methamphetamine, or cocaine) or significant alcohol consumption during pregnancy Mothers with prolonged rupture of the membranes (>21 days duration) Strong suspicion of congenital pneumonia/infection, sepsis Presence of air leaks prior to study entry Evidence of severe birth asphyxia Neonatal seizures prior to study entry Any condition that, in the opinion of the Investigator, would place the neonate at undue risk Participation in another clinical trial of any placebo, drug or biological substance conducted under the provisions of a protocol.

Ages Eligible for Study
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Minimum Age: 1 Hour
Maximum Age: 24 Hours

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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CHF5633<br>Single dose within 24 hours from birth | Drug: CHF5633<br>* Rescue treatment (if needed)<br>|
| Active Comparator: Poractant alfa<br>Single dose within 24 hours from birth | Drug: Poractant alfa<br>* Rescue treatment (if needed)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Oxygen Requirement and Ventilatory Support -- SpO2/FiO2 Ratio | SpO2/FiO2 ratio The oxygen requirement and ventilatory support were assessed through arterial oxygen saturation, measured by pulse oximetry (SpO2 [%]) and ventilator settings, by measuring fraction of inspired oxygen (FiO2[%]) and SpO2/FiO2. Results are shown as change from baseline, summarized at post-treatment timepoints. Definitions: SpO2=Arterial Oxygen saturation by pulse oximetry; FiO2=Fraction of inspired oxygen; Baseline=The last pre-dose measurement taken on Day -1. | Post-treatment Day 1: 30 min, at 1h, 3h, 6h, 12h, 18h, 24 h; Day 2, 3, 5, and 7 | 
| Fraction of Inspired Oxygen (FiO2) (Percent) During the First 24 h and up to Day 7 | Fraction of inspired oxygen (FiO2) (percent) during the first 24 h and up to Day 7. Fraction of inspired oxygen (FiO2 [percent]). Results are shown as change from baseline, summarized at post-treatment time points. Definitions: FiO2=Fraction of inspired oxygen (percent); Baseline=The last pre-dose measurement taken on Day -1; | Post-treatment Day 1: 30 min, at 1h, 3h, 6h, 12h, 18h, 24 h; Day 2, 3, 5, and 7 | 
| Number of Patients With Bronchopulmonary Dysplasia and Mortality | Bronchopulmonary dysplasia and mortality. Results summarize the following items: Number of patients who died and the number of patients who had bronchopulmonary dysplasia (BPD) were assessed by treatment, at 36 weeks post menstrual age (PMA). Number of patients who died by Day 28 post-natal age (PNA). Number of patients with respiratory distress syndrome (RDS)-associated mortality by Day 14 post-natal age (PNA). Definitions: BPD=Bronchopulmonary dysplasia; Mortality/BPD incidence=The incidence of neonates dead within 36-week PMA or alive at 36-week PMA with a diagnosis of BPD; PMA=Post menstrual age; PNA=Post-natal age; RDS=Respiratory distress syndrome; | 36 weeks post menstrual age, Day 14 Post-Natal Age, Day 28 Post-Natal Age | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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neonates, pulmonary surfactant