Clinical trial NCT01651637: First In Human Study on Synthetic Surfactant CHF 5633 in Respiratory Distress Syndrome
Official title: A First in Human Clinical Study on the Safety and Tolerability of Two Escalating Single Doses of CHF 5633 (Synthetic Surfactant) in Preterm Neonates With Respiratory Distress Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Respiratory Distress Syndrome in Premature Infants
Keywords: Respiratory Distress syndrome
Complications of prematurity
Lead sponsor: Chiesi Farmaceutici S.p.A.
Sponsor class: INDUSTRY
First posted: 2012-07-27
Enrollment: 40
Sex: ALL
Minimum age (years): 27
Maximum age (years): 34
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The aim of this study is to investigate the safety and tolerability of intratracheal administration of two different single doses of CHF 5633 in preterm neonates with RDS in terms of adverse events, adverse drug reactions, hematology and biochemistry values, the incidence of major neonatal morbidities including bronchopulmonary dysplasia (BPD) and mortality.

Detailed description: The study will be a multicentre, open-label, single escalating dose, per-cohort design.

Eligibility criteria: Inclusion Criteria:

* Written informed consent obtained by parents/legal representative (according to local regulation) prior to any study-related procedures
* Inborn and outborn, preterm neonates of either sex with a gestational age of 27 weeks up to 33 weeks+6
* Clinical and radiological findings typical of RDS
* Age on admission to the study \< 24 hours from birth
* Requirement of endotracheal intubation for surfactant administration
* Fraction of inspired oxygen (FiO2) \> 0.35 to maintain SpO2 between 90-95 %
* Documentation of normal cranial ultrasound scan

Exclusion Criteria:

* Use of surfactant prior to study entry and need for intratracheal administration of any other treatment (e.g. nitric oxide)
* Known genetic or chromosomal disorders, major congenital anomalies (cardiac malformations, myelomeningocele etc)
* Maternal drug abuse (heroin, methadone, methamphetamine, or cocaine) or significant alcohol consumption during pregnancy
* Clinical chorioamnionitis (Appendix III)
* Strong suspicion of congenital pneumonia/infection, sepsis
* Evidence of severe birth asphyxia or a 5 minutes Apgar score less / equal 3
* Presence of air leaks prior to study entry
* Neonatal seizures prior to study entry
* Mothers with prolonged rupture of the membranes (\> 3 weeks duration)
* Any condition that, in the opinion of the Investigator, would place the neonate at undue risk
* Participation in another clinical trial of any placebo, drug or biological substance conducted under the provisions of a protocol

Primary outcomes:
measure: Monitoring of adverse events following CHF5633 administration
timeFrame: For duration of hospital stay (expected average of 9 weeks)
Secondary outcomes:
measure: CHF 5633 efficacy profile (oxygenation , ventilatory requirements and need for rescue surfactant treatment),systemic absorption and immunogenicity assesment
timeFrame: At min 30, at hrs 1, 3, 6, 12, 24, at days 2, 3, 7 and at days 10, 28, at 36 weeks pma post dosing for ventilatory requirements, at pre-dose and 3 hrs and 24 hrs post dosing for systemic absorption and at 8 wks after administration for immunogenicity
Other outcomes:
Locations:
city: Liverpool
country: United Kingdom
facility: Liverpool Women's Hospital Neonatal Unit Liverpool Women's Hospital
Study officials:
affiliation: Universitäts-Kinderklinik Würzburg (Germany)
name: Christian Speer, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sweet DG, Turner MA, Stranak Z, Plavka R, Clarke P, Stenson BJ, Singer D, Goelz R, Fabbri L, Varoli G, Piccinno A, Santoro D, Speer CP. 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 Neonatal Ed. 2017 Nov;102(6):F497-F503. doi: 10.1136/archdischild-2017-312722. Epub 2017 May 2.