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
Jazyk angličtina Země Velká Británie, Anglie Médium print-electronic
Typ dokumentu klinické zkoušky, časopisecké články, multicentrická studie
PubMed
28465315
PubMed Central
PMC5739829
DOI
10.1136/archdischild-2017-312722
PII: archdischild-2017-312722
Knihovny.cz E-zdroje
- Klíčová slova
- clinical trial, cohort study, respiratory distress syndrome, safety, surfactant,
- MeSH
- fosfatidylcholiny aplikace a dávkování škodlivé účinky MeSH
- intratracheální intubace MeSH
- kohortové studie MeSH
- lidé MeSH
- novorozenec nedonošený MeSH
- novorozenec MeSH
- peptidové fragmenty aplikace a dávkování škodlivé účinky MeSH
- plicní surfaktanty aplikace a dávkování škodlivé účinky MeSH
- protein B asociovaný s plicním surfaktantem aplikace a dávkování škodlivé účinky MeSH
- protein C asociovaný s plicním surfaktantem aplikace a dávkování škodlivé účinky MeSH
- syndrom respirační tísně novorozenců farmakoterapie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
- multicentrická studie MeSH
- Názvy látek
- CHF5633 MeSH Prohlížeč
- fosfatidylcholiny MeSH
- peptidové fragmenty MeSH
- plicní surfaktanty MeSH
- protein B asociovaný s plicním surfaktantem MeSH
- protein C asociovaný s plicním surfaktantem MeSH
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.
Department of Neonatology Institute for the Care of Mother and Child Prague Czech Republic
Department of Neonatology University Children's Hospital Tuebingen Germany
Division of Neonatology General Faculty Hospital and 1st Faculty of Medicine Prague Czech Republic
Global Clinical Development Chiesi Farmaceutici S p A Parma Italy
Neonatal Unit Royal Maternity Hospital Belfast Northern Ireland UK
University Children's Hospital University of Würzburg Würzburg Germany
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ClinicalTrials.gov
NCT01651637
