Trial To Assess The Safety And Tolerability Of Lucinactant For Inhalation In Preterm Neonates 26 to 28 Weeks PMA

Study Overview
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Brief Summary
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This study is to evaluate the safety and tolerability of lucinactant for inhalation, administered as an aerosol in up to four escalating doses to preterm neonates 26 to 28 weeks gestational age who are receiving nCPAP for RDS compared to neonates receiving nCPAP alone.

Detailed Description
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This study was a multicenter, randomized, controlled, open-label, dose-escalation study, conducted to evaluate the safety and tolerability of lucinactant for inhalation in conjunction with nasal continuous positive airway pressure (nCPAP) in comparison with nCPAP alone. The study was to evaluate the safety and tolerability of lucinactant for inhalation, administered as an aerosol in 4 escalating doses. For this study, lucinactant for inhalation refers to the active investigational agent, lyophilized lucinactant, in combination with the prototype investigational delivery device. Reconstituted lyophilized lucinactant was aerosolized by the investigational device and introduced into the nCPAP circuit. Those randomized to the control arm continued to receive nCPAP alone. Dose assignments were unblinded, as the primary objective of this study was safety and tolerability. Preterm neonates with respiratory distress syndrome (RDS) between 26 and 28 completed weeks PMA who were within the first 20 hours after birth and who had successful implementation of controlled nCPAP within 90 minutes of birth were considered to be potential subjects. Before study enrollment, legal guardians were provided a written informed consent form (ICF) for each potential subject.

Official Title
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A Multicenter, Randomized, Open-label, Controlled Trial To Assess The Safety And Tolerability Of Lucinactant For Inhalation In Preterm Neonates 26 to 28 Weeks PMA

Conditions
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Respiratory Distress Syndrome

Intervention / Treatment
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* Combination Product: Lucinactant for inhalation
* Device: nCPAP alone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent from a legally authorized representative. Gestational age 26 to 28 completed weeks post menstrual age (PMA). Successful implementation of controlled nCPAP within 90 minutes after birth. Spontaneous breathing. Chest radiograph consistent with RDS. Within the first 20 hours after birth, have an nCPAP of 5 to 6 cm H2O to maintain oxygen saturation measured by pulse oximetry (SpO2) of 88% to 95% with a fraction of inspired oxygen (FiO2) of 0.25 to 0.50 that is clinically indicated for at least 30 minutes. Transient (<10 minutes) FiO2 excursions below 0.25 or above 0.50 did not reset the 30 minute requirement. Exclusion Criteria: Heart rate that cannot be stabilized above 100 beats/minute within 5 minutes of birth. Recurrent episodes of apnea occurring after the initial newborn resuscitation period (ie, 10 minutes after birth) requiring intermittent positive pressure breaths using inflating pressures above the set CPAP pressure administered manually or mechanically through any patient interface. A 5 minute Apgar score < 5. Major congenital malformation(s) and cranial/facial abnormalities that preclude nCPAP, diagnosed antenatally or immediately after birth. Other diseases or conditions potentially interfering with cardiopulmonary function (eg, hydrops fetalis or congenital infection such as TORCH). Known or suspected chromosomal abnormality or syndrome. Premature rupture of membranes (PROM) > 2 weeks. Evidence of hemodynamic instability requiring vasopressors or steroids for hemodynamic support and/or presumed clinical sepsis. Need for endotracheal intubation and mechanical ventilation. Has been administered: another investigational agent or investigational medical device, any other surfactant agent, steroid treatment after birth.

Ages Eligible for Study
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Minimum Age: 26 Weeks
Maximum Age: 28 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: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 50 mg/kg<br>Lucinactant for inhalation 50 mg total phospholipids (TPL)/kg with nCPAP 1 repeat dose allowed if repeat dosing criteria are met. | Combination Product: Lucinactant for inhalation<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®;|
| Experimental: 75 mg/kg<br>Lucinactant for inhalation 75 mg TPL/kg with nCPAP 1 repeat dose allowed if repeat dosing criteria are met. | Combination Product: Lucinactant for inhalation<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®;|
| Experimental: 100 mg/kg<br>Lucinactant for inhalation 100 mg TPL/kg with nCPAP 1 repeat dose allowed if repeat dosing criteria are met. | Combination Product: Lucinactant for inhalation<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®;|
| Experimental: 150 mg/kg<br>Lucinactant for inhalation 150 mg TPL/kg with nCPAP 1 repeat dose will be allowed if repeat dosing criteria are met. | Combination Product: Lucinactant for inhalation<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®;|
| Active Comparator: nCPAP alone<br>nCPAP therapy alone | Device: nCPAP alone<br>* nCPAP therapy<br>* Other names: nasal continuous positive airway pressure;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Peri-Dosing Adverse Events - Initial Dose | Number of Participants with adverse events that were experienced during the initial study treatment | Randomization to 24 Hours Post Randomization | 
| Number of Participants With Air Leak | Number of participants with air leak (includes pneumothorax, pulmonary interstitial emphysema (PIE), pneumomediastinum, pneumopericardium, subcutaneous emphysema) | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Worsening of Respiratory Status Criteria | Number of participants with worsening in one of 12 respiratory status criteria through 72 hours post randomization (need for additional surfactant therapy, desaturation < 80%, heart rate < 100 bpm, sustained fraction of inspired oxygen (FiO2) > 0.50, arterial carbon dioxide (PCO2) > 65 mmHg, sustained apnea, persistent arterial pH < 7.2, intubation for any reason, nCPAP > 7 cmH2O, initiation of intermittent positive pressure ventilation, death, principal investigator determination of worsening status) | Randomization to 72 Hours Post Randomization | 
| Bronchopulmonary Dysplasia | Number of participants with bronchopulmonary dysplasia (BPD) and number of participants alive and without BPD at 36 weeks post-menstrual age (PMA) | Randomization to 36 weeks PMA | 
| Number of Participants With Nasal Continuous Positive Airway Pressure (nCPAP) Failure | Participants who required intubation for mechanical ventilation or surfactant administration were defined as having failed nCPAP | Randomization to 72 Hours Post Randomization | 
| Death | Number of participants who died during the study | Randomization to 36 weeks PMA | 
| FiO2 | Observed and change from baseline measurements for fraction of inspired oxygen (FiO2). Values represent the amount (fraction) of oxygen in the air the participant inspires; the values themselves do not have units. The normal amount of oxygen in air (room air) is 21%, or 0.21. | Randomization to 72 hours post randomization | 
| Number of Participants With Complications of Prematurity | Number of participants with pre-specified common complications of prematurity. | Randomization to 36 weeks PMA |