Objective CHF5633 (Chiesi Farmaceutici S.p.A., Parma, Italy) is the first fully synthetic surfactant enriched by peptide analogues of two human surfactant proteins. We planned to assess safety and tolerability of CHF5633 and explore preliminary efficacy.
Design Multicentre cohort study.
Patients Forty infants from 27+0 to 33+6 weeks gestation with respiratory distress syndrome requiring fraction of inspired oxygen (FiO2) ≥0.35 were treated with a single dose of CHF5633 within 48 hours after birth. The first 20 received 100 mg/kg and the second 20 received 200 mg/kg.
Outcome measures Adverse events (AEs) and adverse drug reactions (ADRs) were monitored with complications of prematurity considered AEs if occurring after dosing. Systemic absorption and immunogenicity were assessed. Efficacy was assessed by change in FiO2 after dosing and need for poractant-alfa rescue.
Results Rapid and sustained improvements in FiO2 were observed in 39 (98%) infants. One responded neither to CHF5633 nor two poractant-alfa doses. A total of 79 AEs were experienced by 19 infants in the 100 mg/kg cohort and 53 AEs by 20 infants in the 200 mg/kg cohort. Most AEs were expected complications of prematurity. Two unrelated serious AEs occurred in the second cohort. One infant died of necrotising enterocolitis and another developed viral bronchiolitis after discharge. The single ADR was an episode of transient endotracheal tube obstruction following a 200 mg/kg dose. Neither systemic absorption, nor antibody development to either peptide was detected.
Conclusions Both CHF5633 doses were well tolerated and showed promising clinical efficacy profile. These encouraging data provide a basis for ongoing randomised controlled trials.
Trial registration number ClinicalTrials.gov NCT01651637.
- respiratory distress syndrome
- cohort study
- clinical trial
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Contributors DGS recruited patients, was on the safety monitoring board, helped with data analysis, drafted the initial manuscript and approved the final manuscript as submitted. MT recruited patients, helped with manuscript editing and approved the final manuscript and was part of the safety monitoring board. ZS and RP recruited patients and approved the final manuscript. PC recruited patients and helped with manuscript preparation and approved the final manuscript. BS, RG, DSi recruited patients, were on the safety monitoring board, helped with manuscript editing and approved the final manuscript. LF and GV conceptualised and designed the study,assisted with data analysis and approved the final manuscript. AP and DS helped with data presentation and analysis and approved the final manuscript. CPS conceptualised and designed the study, recruited patients, was the chairman of the safety monitoring board, assisted with data analysis and approved the final manuscript.
Funding Chiesi Farmaceutici S.p.A. (Italy).
Competing interests LF, DS, AP and GV are full employees of Chiesi Farmaceutici S.p.A., sponsor of the study. DGS has previously acted in an advisory capacity for Chiesi Pharmaceuticals UK. CPS is consultant for Chiesi Farmaceutici S.p.A. (Italy). MT serves as a consultant to Chiesi Farmaceutici S.p.A. (Italy) with respect to the development of CHF5633 on behalf of the University of Liverpool without deriving any personal benefit from this consultancy. The remaining authors have no conflict of interest to declare. All authors received clinical research funds from Chiesi Farmaceutici S.p.A. as site investigators for this study.
Ethics approval Ethics review boards for each institution in each country.
Provenance and peer review Not commissioned; externally peer reviewed.
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