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

Study Overview
=================
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.

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

Conditions
-----------------
Respiratory Distress Syndrome in Premature Infants

Intervention / Treatment
-----------------
* Drug: synthetic surfactant (CHF5633)


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 27 Weeks
Maximum Age: 34 Weeks

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Synthetic Surfactant<br>Cohort Design | Drug: synthetic surfactant (CHF5633)<br>* 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<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Respiratory Distress syndrome, Complications of prematurity