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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: 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.Multicentre cohort study.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.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.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.Both CHF5633 doses were well tolerated and showed promising clinical efficacy profile. These encouraging data provide a basis for ongoing randomised controlled trials.ClinicalTrials.gov NCT01651637.

SUBMITTER: Sweet DG

PROVIDER: S-EPMC5739829 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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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.

Sweet David G DG Turner Mark A MA Straňák Zbyněk Z Plavka Richard R Clarke Paul P Stenson Ben J BJ Singer Dominique D Goelz Rangmar R Fabbri Laura L Varoli Guido G Piccinno Annalisa A Santoro Debora D Speer Christian P CP

Archives of disease in childhood. Fetal and neonatal edition 20170502 6

<h4>Objective</h4>CHF5633 (Chiesi Farmaceutici S.p.A., Parma, Italy) is the first fully synthetic surfactant enriched by peptide analogues of <i>two</i> human surfactant proteins. We planned to assess safety and tolerability of CHF5633 and explore preliminary efficacy.<h4>Design</h4>Multicentre cohort study.<h4>Patients</h4>Forty infants from 27<sup>+0</sup> to 33<sup>+6</sup> weeks gestation with respiratory distress syndrome requiring fraction of inspired oxygen (FiO<sub>2</sub>) ≥0.35 were tr ...[more]

PMID: 28465315

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Project description:BackgroundRespiratory distress syndrome (RDS), a disorder of primary surfactant deficiency resulting in pulmonary insufficiency, remains a significant problem for preterm neonates. Associations between genetic variants of surfactant proteins and RDS have been reported, but haplotypes of the surfactant protein B gene (SFTPB) have not been studied. The aim of the study was to prove the hypothesis that certain haplotypes of SFTPB may be protective or risk factors for RDS.MethodsThe study was performed with 149 preterm infants, born <34 weeks of gestation, with 86 infants with mild RDS or without RDS (control group) and 63 infants with severe RDS (patient group). RDS was considered severe if multiple doses of exogenous surfactant and/or mechanical ventilation within the first 72 h of life were needed. The venous blood sample was used for the analysis of gene polymorphisms associated with RDS, genotyping, and haplotype estimation. Multivariate logistic regression analysis and the odds ratio were calculated to detect the contribution of the studied variables to the development of RDS.ResultsA new association of the common single nucleotide polymorphism (SNP) rs2304566 with RDS in premature infants was detected. Analysis of rs2304566 polymorphisms using a logistic regression model showed that there are two significant predictors inversely related to the occurrence of RDS (Apgar score of 5 min, CT and TT genotype in rs2304566 polymorphism). Gestational age, birth weight, and sex have border significance. Moreover, in the patient group, the frequency of the GATGACA haplotype in the SFTPB gene was lower (p = 0.037), and the GATGGCA haplotype was higher (p = 0.059) in comparison with the control group.ConclusionThe common haplotype GATGACA of the SFTPB gene can be protective against RDS in preterm infants. The trend of a higher frequency of GATGGCA in the SFTPB gene in infants with severe RDS suggests that this haplotype may be a risk factor for RDS susceptibility.

Dataset Information

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.

Publications

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.

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