A Safety and Efficacy Study of Lucinactant for Inhalation in Preterm Neonates 26 to 32 Weeks Gestational Age

Study Overview
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Brief Summary
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This study is to evaluate the safety and efficacy of lucinactant for inhalation in conjunction with nCPAP, in comparison to nCPAP alone, in preterm neonates with RDS, as assessed by the incidence of and time to respiratory failure and/or death due to RDS in the first 72 hours and 28 days of life. Half of the subjects will receive lucinactant for inhalation and half will receive standard of care (nCPAP alone).

Detailed Description
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An unmet medical need exists for a means to deliver surfactant replacement therapy (SRT) to preterm neonates with RDS supported with nCPAP early in the course of the disease. This strategy has the potential to improve RDS prior to the development of respiratory failure, thereby avoiding the need for endotracheal intubation and mechanical ventilation (MV), or reduce the duration of MV, and the resultant potential for morbidity and complications. The ability to administer SRT via aerosol has the potential to address this unmet need. Lucinactant for inhalation (AEROSURF) is an investigational drug-device combination product, designed to deliver aerosolized SRT to preterm neonates with RDS who are being supported with nCPAP. The drug component of lucinactant for inhalation is lyophilized lucinactant, a lyophilized form of SURFAXIN® (lucinactant) Intratracheal Suspension. The device component, the AEROSURF Delivery System (ADS), the next-generation device following use of the prototype device in earlier trials, uses novel technology to aerosolize lucinactant for inhalation. This study evaluates the safety and efficacy of lucinactant for inhalation in conjunction with nCPAP, in comparison to nCPAP alone, in preterm neonates with RDS, as assessed by pre-specified outcome measures. In addition, this study will evaluate the device and the ability to administer up to 3 repeat doses.

Official Title
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A Multinational, Multicenter, Masked, Randomized, Controlled Study to Assess the Safety and Efficacy of Lucinactant for Inhalation Versus nCPAP Alone in Preterm Neonates 26 to 32 Weeks Gestational Age With RDS

Conditions
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Respiratory Distress Syndrome, Newborn

Intervention / Treatment
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* Combination Product: Lucinactant for Inhalation
* Other: nCPAP Only


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed ICF from legally authorized representative. Gestational age: 26 to 32+6 weeks PMA. Successful implementation of non-invasive support or ventilation within 30 minutes after birth. Spontaneous breathing. Investigator determination of RDS. A chest x-ray should be obtained before treatment to confirm the diagnosis. Within the first 6 hours after birth, requires an nCPAP of 5 to 7 cm H2O that is clinically indicated for at least 15 minutes with an FiO2 > 0.25 to ≤ 0.35 to maintain SpO2 of 90% to 95%. Exclusion Criteria: A heart rate that cannot be stabilized above 100 bpm within 5 minutes of birth. Recurrent episodes of apnea requiring positive pressure ventilation. A 5 minute Apgar score < 5. Major congenital malformation(s) or craniofacial abnormalities that preclude the use of nCPAP. Clinically significant diseases or conditions other than RDS which could potentially interfere with cardiopulmonary function. A known or suspected chromosomal abnormality or syndrome. Premature rupture of membranes > 3 weeks. Hemodynamic instability requiring vasopressors or steroids for hemodynamic support and/or presumed clinical sepsis. A need for intubation and/or invasive mechanical ventilation at any time before enrollment into the study. The administration (or plan for administration) of another investigational agent or investigational medical device, any other surfactant agent, or systemic corticosteroids. Presence of air leak on the baseline chest radiograph or diagnosed via ultrasound or illumination.

Ages Eligible for Study
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Minimum Age: 30 Minutes
Maximum Age: 6 Hours

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
Interventional Model Description: This study is a multinational, multicenter, double-blind (masked), parallel group, randomized, controlled study, in preterm neonates 26 to 32 completed weeks post-menstrual age (PMA).
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lucinactant (160 mg/kg) + nCPAP<br>Lucinactant for inhalation, 160 mg total phospholipids (TPL)/kg Delivered as an aerosol once, with up to 3 repeats of 80 mg/kg allowed within 36 hours of birth | Combination Product: Lucinactant for Inhalation<br>* A drug-device combination product that delivers aerosolized SRT to preterm neonates with RDS who are being supported with nasal continuous positive airway pressure (nCPAP).<br>* Other names: AEROSURF;|
| Sham Comparator: nCPAP Only<br>nCPAP Only as sham comparator. Bubble nCPAP is standard of care. Treatment time behind barrier to match active treatment delivery time | Other: nCPAP Only<br>* Nasal continuous positive airway pressure (nCPAP) alone<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 | Number of participants with respiratory failure due to RDS or death. Respiratory failure due to RDS is defined as intubation for mechanical ventilation and/or surfactant administration | 28 days of life | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number With BPD | Number of participants with bronchopulmonary dysplasia (BPD) | 36 weeks post-menstrual age (PMA) | 
| Mortality | All-cause mortality | 36 weeks PMA or 28 days of life (whichever is later) | 
| Number of Participants With Common Complications of Prematurity | Number of participants with complications including intraventricular hemorrhage, periventricular leukomalacia, pulmonary hemorrhage, apnea, necrotizing enterocolitis, patent ductus arteriosus, acquired sepsis, and retinopathy of prematurity. | 36 weeks PMA | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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intubation, surfactant, continuous positive airway pressure, aerosol, respiratory distress syndrome