The Safety and Efficacy of Lucinactant for Inhalation in Premature Neonates 26 to 32 Weeks Gestational Age

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the safety and efficacy of lucinactant for inhalation administered as an aerosolized dose in two doses to preterm neonates 26 - 32 weeks gestational age who are receiving nasal continuous positive airway pressure (nCPAP) for Respiratory Distress Syndrome (RDS) compared to neonates receiving nCPAP alone.

Detailed Description
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The purpose of this study is to investigate the safety and efficacy of lucinactant for inhalation in preterm neonates 26 to 32 completed weeks post-menstrual age (PMA). Efficacy and safety are based on clinical evaluations. The endpoints specified are similar to those in Protocols 03-CL-1201 and 03-CL-1401 to allow for potential comparison and pooling of results. The objective of this study is to evaluate the safety and efficacy of lucinactant for inhalation in conjunction with nCPAP, compared to nCPAP alone, in preterm neonates with RDS, as assessed by the time to and incidence of respiratory failure and/or death due to RDS over the first 72 hours of life, the incidence of bronchopulmonary dysplasia (BPD) at 36 weeks PMA, and change in physiologic parameters (FiO2 and PCO2) over the first 72 hours of life.

Official Title
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A Multinational, Multicenter, Masked, Randomized, Controlled Study to Assess The Safety and Efficacy of Lucinactant for Inhalation in Preterm Neonates 26 to 32 Weeks Gestational Age With Respiratory Distress Syndrome

Conditions
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Respiratory Distress Syndrome

Intervention / Treatment
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* Drug: Lucinactant delivered via investigational delivery device
* Drug: nCPAP


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent form (ICF) from legally authorized representative 26 0/7 to 32 6/7 completed weeks gestation PMA Successful implementation of non-invasive support or ventilation within 90 minutes after birth Spontaneous breathing Chest radiograph consistent with RDS Within the first 20 hours after birth requires an nCPAP of 5 to 7 centimeters water (cmH2O) with a fraction of inspired oxygen (FiO2) of ≥ 0.25 (>0.21 for neonates 26-28 weeks PMA) to 0.40 that is clinically indicated for at least 30 minutes to maintain oxygen by pulse oximetry (SpO2) of 90% to 95%. Transient (<10 minutes) FiO2 excursions outside this range do not reset the 30-minute requirement. Exclusion Criteria: A heart rate that cannot be stabilized above 100 beats per minute (bpm) within 5 minutes of birth Recurrent episodes of apnea requiring positive pressure ventilation (PPV) administered manually or mechanically through any patient interface A 5 minute Apgar score < 5 Major congenital malformation(s) or craniofacial abnormalities that preclude the use of nCPAP, diagnosed antenatally or immediately after birth Clinically significant diseases or conditions other than RDS which could potentially interfere with cardiopulmonary function (e.g. congenital heart disease, hydrops fetalis or congenital infection) A known or suspected chromosomal abnormality or syndrome Premature rupture of membranes (PROM) > 3 weeks Hemodynamic instability requiring vasopressors or steroids for hemodynamic support and/or presumed clinical sepsis A need for intubation and/or mechanical ventilation at any time before enrollment into the study The administration (or plan for administration) of any the following: Another investigational agent or investigational medical device Any other surfactant agent Systemic corticosteroids (other than antenatal steroids already received) Presence of air leak (pneumothorax, pneumomediastinum, pneumopericardium, subcutaneous emphysema, or definite evidence of pulmonary interstitial emphysema (PIE)) on the baseline chest radiograph

Ages Eligible for Study
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Minimum Age: 26 Weeks
Maximum Age: 32 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aerosolized lucinactant (low dose)<br>Lucinactant for inhalation with nCPAP; up to 2 repeat doses will be allowed if repeat dosing criteria are met. | Drug: Lucinactant delivered via investigational delivery device<br>* Lucinactant for inhalation refers to the active investigational agent lucinactant in combination with the investigational delivery device (drug-device combination product)<br>* Other names: AEROSURF;Drug: nCPAP<br>* Nasal CPAP<br>|
| Experimental: Aerosolized lucinactant (high dose)<br>Lucinactant for inhalation with nCPAP; up to 2 repeat doses will be allowed if repeat dosing criteria are met. | Drug: Lucinactant delivered via investigational delivery device<br>* Lucinactant for inhalation refers to the active investigational agent lucinactant in combination with the investigational delivery device (drug-device combination product)<br>* Other names: AEROSURF;Drug: nCPAP<br>* Nasal CPAP<br>|
| Active Comparator: nasal CPAP<br>nCPAP alone | Drug: nCPAP<br>* Nasal CPAP<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Respiratory Failure or Death Due to Respiratory Distress Syndrome (RDS) | Number of participants who had respiratory failure due to RDS or death due to RDS; known as nasal continuous positive airway pressure (nCPAP) failure | 72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Respiratory Failure or Death Due to RDS | Incidence of Respiratory Failure or Death Due to RDS by Intubation or Failure Criteria | 72 hours | 
| Time to nCPAP Failure | Time from birth to nCPAP Failure | 72 hours | 
| Incidence of Respiratory Failure or Death Due to RDS With Poisson Distribution Modeling | The measure tests the differences between treatments on respiratory failure or death due to RDS using Poisson distribution modeling, which accounts for the time over which the event could have occurred. | 72 hours | 
| Incidence of Respiratory Failure or Death Due to RDS | Incidence of Respiratory Failure or Death due to RDS by Intubation or Failure Criteria | 28 days | 
| Number of Participants With Bronchopulmonary Dysplasia (BPD) | Summarizes the number of participants with BPD or alive without BPD | 36 weeks post-menstrual age (PMA) |