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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

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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; Turner, Mark A; Straňák, Zbyněk; Plavka, Richard; Clarke, Paul; Stenson, Ben J; Singer, Dominique; Goelz, Rangmar; Fabbri, Laura; Varoli, Guido; Piccinno, Annalisa; Santoro, Debora; Speer, Christian P.

In: ARCH DIS CHILD-FETAL, Vol. 102, No. 6, 11.2017, p. F497-F503.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Sweet, DG, Turner, MA, Straňák, Z, Plavka, R, Clarke, P, Stenson, BJ, Singer, D, Goelz, R, Fabbri, L, Varoli, G, Piccinno, A, Santoro, D & Speer, CP 2017, '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', ARCH DIS CHILD-FETAL, vol. 102, no. 6, pp. F497-F503. https://doi.org/10.1136/archdischild-2017-312722

APA

Sweet, D. G., Turner, M. A., Straňák, Z., Plavka, R., Clarke, P., Stenson, B. J., Singer, D., Goelz, R., Fabbri, L., Varoli, G., Piccinno, A., Santoro, D., & Speer, C. P. (2017). 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. ARCH DIS CHILD-FETAL, 102(6), F497-F503. https://doi.org/10.1136/archdischild-2017-312722

Vancouver

Sweet DG, Turner MA, Straňák Z, Plavka R, Clarke P, Stenson BJ et al. 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. ARCH DIS CHILD-FETAL. 2017 Nov;102(6):F497-F503. https://doi.org/10.1136/archdischild-2017-312722

Bibtex

@article{6a5116967afd4079b3f3c0d247fdae07,
title = "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 = "Cohort Studies, Female, Humans, Infant, Newborn, Infant, Premature, Intubation, Intratracheal, Male, Peptide Fragments, Phosphatidylcholines, Pulmonary Surfactant-Associated Protein B, Pulmonary Surfactant-Associated Protein C, Pulmonary Surfactants, Respiratory Distress Syndrome, Newborn, Clinical Trial, Journal Article, Multicenter Study",
author = "Sweet, {David G} and Turner, {Mark A} and Zbyn{\v e}k Stra{\v n}{\'a}k and Richard Plavka and Paul Clarke and Stenson, {Ben J} and Dominique Singer and Rangmar Goelz and Laura Fabbri and Guido Varoli and Annalisa Piccinno and Debora Santoro and Speer, {Christian P}",
note = "{\textcopyright} 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.",
year = "2017",
month = nov,
doi = "10.1136/archdischild-2017-312722",
language = "English",
volume = "102",
pages = "F497--F503",
journal = "ARCH DIS CHILD-FETAL",
issn = "1359-2998",
publisher = "BMJ PUBLISHING GROUP",
number = "6",

}

RIS

TY - JOUR

T1 - 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

AU - Sweet, David G

AU - Turner, Mark A

AU - Straňák, Zbyněk

AU - Plavka, Richard

AU - Clarke, Paul

AU - Stenson, Ben J

AU - Singer, Dominique

AU - Goelz, Rangmar

AU - Fabbri, Laura

AU - Varoli, Guido

AU - Piccinno, Annalisa

AU - Santoro, Debora

AU - Speer, Christian P

N1 - © 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.

PY - 2017/11

Y1 - 2017/11

N2 - 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.

AB - 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.

KW - Cohort Studies

KW - Female

KW - Humans

KW - Infant, Newborn

KW - Infant, Premature

KW - Intubation, Intratracheal

KW - Male

KW - Peptide Fragments

KW - Phosphatidylcholines

KW - Pulmonary Surfactant-Associated Protein B

KW - Pulmonary Surfactant-Associated Protein C

KW - Pulmonary Surfactants

KW - Respiratory Distress Syndrome, Newborn

KW - Clinical Trial

KW - Journal Article

KW - Multicenter Study

U2 - 10.1136/archdischild-2017-312722

DO - 10.1136/archdischild-2017-312722

M3 - SCORING: Journal article

C2 - 28465315

VL - 102

SP - F497-F503

JO - ARCH DIS CHILD-FETAL

JF - ARCH DIS CHILD-FETAL

SN - 1359-2998

IS - 6

ER -