First In Human Study on Synthetic Surfactant CHF 5633 in Respiratory Distress Syndrome

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

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.

Study Overview

• Status: Completed
• Conditions: Respiratory Distress Syndrome in Premature Infants
• Intervention / Treatment: Drug: synthetic surfactant (CHF5633)

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Liverpool, United Kingdom
    • Liverpool Women's Hospital Neonatal Unit Liverpool Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 7 months (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Synthetic Surfactant; Cohort Design	Drug: synthetic surfactant (CHF5633); CHF5633 100 mg/kg; CHF5633 200 mg/kg synthetic surfactant sterile suspension in 3.0 ml glass vials with a total concentration of 80 mg/ml for intratracheal administration. Single administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Monitoring of adverse events following CHF5633 administration	For duration of hospital stay (expected average of 9 weeks)

Secondary Outcome Measures

Outcome Measure	Time Frame
CHF 5633 efficacy profile (oxygenation , ventilatory requirements and need for rescue surfactant treatment),systemic absorption and immunogenicity assesment	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

Collaborators and Investigators

• Sponsor: Chiesi Farmaceutici S.p.A.
• Investigators: Principal Investigator: Christian Speer, MD, Universitäts-Kinderklinik Würzburg (Germany)

Publications and helpful links

General Publications

• 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.

Helpful Links

• Study Record on EU Clinical Trials Register including results

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (ACTUAL): January 23, 2015
• Study Completion (ACTUAL): January 23, 2015

Study Registration Dates

• First Submitted: April 20, 2012
• First Submitted That Met QC Criteria: July 26, 2012
• First Posted (ESTIMATE): July 27, 2012

Study Record Updates

• Last Update Posted (ACTUAL): July 31, 2020
• Last Update Submitted That Met QC Criteria: July 30, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Respiratory Distress syndrome; Complications of prematurity
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Disease; Infant, Newborn, Diseases; Infant, Premature, Diseases; Syndrome; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Respiratory System Agents; Pulmonary Surfactants
• Other Study ID Numbers: CCD-1011-PR-0059

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO