A first-in-human clinical study of a new SP-B and SP-C enriched synthetic surfactant (CHF5633) in preterm babies with respiratory distress syndrome

Abstract

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.

Keywords: clinical trial; cohort study; respiratory distress syndrome; safety; surfactant.

Conflict of interest statement

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.

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Figures

Figure 1

Patients’ disposition. FiO2, fraction of inspired oxygen; NEC, necrotising enterocolitis; RDS, respiratory distress syndrome.

Figure 2

Fraction of inspired oxygen (FiO2) in all babies and corresponding mean airway pressure (MAP) in those undergoing mechanical ventilation 24 hours after CHF5633 in the two dosing cohorts. Bars represent SD. Data offset slightly to improve clarity. Inset shows same data over first 3 hours to illustrate speed of onset of action of effect.