Synthetic Surfactant CHF5633 Compared with Poractant Alfa in the Treatment of Neonatal Respiratory Distress Syndrome: A Multicenter, Double-Blind, Randomized, Controlled Clinical Trial

J Pediatr. 2020 Oct:225:90-96.e1. doi: 10.1016/j.jpeds.2020.06.024. Epub 2020 Jun 14.

Abstract

Objective: To compare efficacy and safety of a new synthetic surfactant, CHF5633, enriched with surfactant proteins, SP-B and SP-C peptide analogues, with porcine surfactant, poractant alfa, for the treatment of respiratory distress syndrome in infants born preterm.

Study design: Neonates born preterm on respiratory support requiring fraction of inspired oxygen (FiO2) ≥0.30 from 240/7 to 266/7 weeks and FiO2 ≥0.35 from 270/7 to 296/7 weeks of gestation to maintain 88%-95% oxygen saturation were randomized to receive 200 mg/kg of CHF5633 or poractant alfa. If necessary, redosing was given at 100 mg/kg. Efficacy end points were oxygen requirement (FiO2, respiratory severity score [FiO2 × mean airway pressure]) in the first 24 hours, 7 and 28 days, discharge home, and/or 36 weeks of postmenstrual age; mortality and bronchopulmonary dysplasia at 28 days and 36 weeks of PMA. Adverse events and immunogenicity were monitored for safety.

Results: Of the 123 randomized neonates, 113 were treated (56 and 57 in CHF5633 and poractant alfa groups, respectively). In both arms, FiO2 and respiratory severity score decreased from baseline at all time points (P < .001) with no statistically significant differences between groups. Rescue surfactant use (19 [33.9%] vs 17 [29.8%]), bronchopulmonary dysplasia (31 [55.4%] and 32 [56.1%]), and mortality at day 28 (4 [7.1%] and 3 [5.3%]) were similar in the CHF5633 and poractant alfa groups, respectively. In 2 (3.4%) and 1 (1.7%) neonates, adverse drug reactions were reported in CHF5633 and poractant alfa groups, respectively. No immunogenicity was detected.

Conclusions: Treatment with CHF5633 showed similar efficacy and safety as poractant alfa in neonates born preterm with moderate-to-severe respiratory distress syndrome.

Trial registration: ClinicalTrials.gov: NCT02452476.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Products / therapeutic use*
  • Biomarkers / metabolism
  • Bronchopulmonary Dysplasia / drug therapy
  • Double-Blind Method
  • Female
  • Humans
  • Infant, Newborn
  • Infant, Premature
  • Male
  • Oxygen / therapeutic use
  • Peptide Fragments / therapeutic use*
  • Phosphatidylcholines / therapeutic use*
  • Phospholipids / therapeutic use*
  • Pulmonary Surfactant-Associated Protein B / therapeutic use*
  • Pulmonary Surfactant-Associated Protein C / therapeutic use*
  • Pulmonary Surfactants / therapeutic use*
  • Respiratory Distress Syndrome, Newborn / drug therapy*
  • Treatment Outcome

Substances

  • Biological Products
  • Biomarkers
  • CHF5633
  • Peptide Fragments
  • Phosphatidylcholines
  • Phospholipids
  • Pulmonary Surfactant-Associated Protein B
  • Pulmonary Surfactant-Associated Protein C
  • Pulmonary Surfactants
  • poractant alfa
  • Oxygen

Associated data

  • ClinicalTrials.gov/NCT02452476