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

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.

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;

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;

Normal breathing (room air) within 24 hours

The number of patients with at least one reading of FiO2 equal to 21% (i.e. corresponding to room air for oxygen concentration) within 24 hours from first dose of surfactant was evaluated.

Number of patients with the need for re-dosing (use of rescue surfactant).

The number of patients requiring at least one surfactant rescue dose (i.e. re-dosing with the study drug) at any time during the study was evaluated.

Time to reach normal breathing (room air) within 24 hours.

The median time to reach normal breathing (room air) within 24 hours from first dose of surfactant was evaluated. These are the patients who contributed to the results in the outcome measure 'Normal Breathing (room air) within 24 hours'.

The inflammatory status of the patients was assessed (in a subgroup of babies who required endotracheal intubation for mechanical ventilation, when feasible). This was performed by measuring the concentration of specific biomarkers of inflammation in tracheal aspirates. The biomarkers measured were: Interleukin 1β, Interleukin 6, Interleukin 8, Myeloperoxidase, and Tumor Necrosis Factor-Alpha.

The total protein content in tracheal aspirates was measured as an endogenous marker of dilution to calculate the extent to which epithelial lining fluid (ELF) was diluted during the tracheal aspirate procedure. To adjust for variation during the collection of tracheal aspirates, the measured cytokines values were normalized to the total protein. Results are presented as change from baseline in pg/mg total protein and were evaluated by descriptive statistics.

Definition:

Baseline=The last pre-dose measurement taken on Day -1;

Immunogenicity was assessed by measuring antibodies to SP-B analogue (CHF 5736.03) and to SP-C analogue (CHF 4902.03), contained in CHF 5633.

Results are expressed as the titre (i.e. serum dilution) at which the sample had an absorbance of 0.069 (background) for SP-C Analogue (CHF 4902.03) CHF or an absorbance of 0.05 for SP-B Analogue (CHF 5736.03) in a microplate reader. The positive control serum was diluted in buffer solution and the maximum binding for the positive control was determined at dilutions < 1/12.5 for SPC and <1/100 for SPB. Test samples for immunogenicity were analyzed by using negative and positive controls. By definition, titer <12.5 for CHF-4902.03 and <100 for CHF-5736.02 show that the test serum had an absorbance equal to background at the same dilution at which the positive control had the maximum binding, implying absence of antibodies.