The Safety and Preliminary Tolerability of Lyophilized Lucinactant in Adults With Coronavirus Disease 2019 (COVID-19)

Study Overview
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Brief Summary
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This is a multicenter, single-treatment study. Subjects will consist of adults with COVID-19 associated acute lung injury who are being cared for in a critical care environment.

Detailed Description
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This is a multicenter, single-treatment study. Subjects will consist of adults with COVID-19 associated acute lung injury who are being cared for in a critical care environment. Lucinactant is a synthetic surfactant that, in its liquid form (SURFAXIN®), is approved by the United States Food and Drug Administration (NDA 021746) for the prevention of respiratory distress syndrome (RDS) in premature infants at high risk for RDS. It has been studied in over 2000 children and adults. Preliminary data from animal and adult human studies indicate that lucinactant may be able to benefit those with acute respiratory distress syndrome (ARDS) in the context of COVID-19 infection, improving oxygenation and lung compliance. When given to intubated patients, Lucinactant could potentially decrease the duration of ventilation. Lucinactant has an extensive safety profile in different patient populations for different indications. It is hypothesized that lucinactant may improve the respiratory status of patients suffering from COVID-19.

Official Title
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A Multicenter, Single-Treatment Study to Assess the Safety and Tolerability of Lyophilized Lucinactant in Adults With COVID-19 Associated Acute Lung Injury

Conditions
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COVID-19, Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS)

Intervention / Treatment
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* Drug: Lucinactant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed and dated informed consent form (ICF) by the subject or legally authorized representative; Age 18-75 (inclusive); Assay positive for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus, preferably by polymerase chain reaction (PCR); Endotracheal intubation and mechanical ventilation (MV), within 7 days of initial intubation; In-dwelling arterial line; PaO2/FiO2 (P/F) ratio < 300; Mean blood pressure ≥ 65 mmHg, immediately before enrollment; Bilateral infiltrates seen on frontal chest radiograph. Exclusion Criteria: Life expectancy < 48 hours or do not resuscitate orders; Severe lung disease (home O2, forced expiratory volume at one second [FEV1] < 2 liters) not likely to respond to therapy or profound hypoxemia (ie, oxygen index [OI] ≥ 25 or P/F ratio < 100); Severe renal impairment (creatinine clearance < 30 mL/min); Within the last 6 months has received, or is currently receiving, immunosuppression therapy (azathioprine, cyclophosphamide or methotrexate) or any transplant recipient; Clinically significant cardiac disease that adversely effects cardiopulmonary function: Acute coronary syndromes or active ischemic heart disease (as assessed by the PI using troponin and ECG) Cardiac ejection fraction < 40% (if known); Need for multiple-dose vasopressors to support blood pressure (single dose vasopressors, such as Levophed™ ≤ 0.1 mcg/kg/min are allowed); Cardiogenic pulmonary edema as the etiology of the current respiratory distress; Evidence of myocarditis or pericarditis; Neuromuscular disease; Neutropenia (ANC < 1000); Active malignancy that impacts treatment decisions or life expectancy related to the trial; Suspected concomitant bacterial or other viral lung infection. Bacterial infection defined as white blood count (WBC) > 15k and positive blood/urine/sputum culture results within 72 hours.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

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
Intervention Model: Single Group Assignment
Interventional Model Description: Open-label, single treatment of reconstituted Lucinactant, delivered as an intratracheal liquid.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lyophilized Lucinactant<br>Lyophilized Lucinactant reconstituted with sterile water for injection | Drug: Lucinactant<br>* Lucinactant administered as a liquid at a dose of 80 mg total phospholipids (TPL)/kg lean body weight delivered<br>* Other names: Sinapultide (KL4) Surfactant;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Oxygen Index (OI) | Change from baseline in OI. OI is an index value, calculated as (Mean Airway Pressure [Paw]) x (Fraction of Inspired Oxygen [FiO2]) x (100) / (Partial Pressure of Oxygen [PaO2]) measured using mean and standard deviation. It is a calculation that measures the fraction of inspired oxygen and its usage within the body, and a lower value is better. Values can range from 0 to 1000; values under 25 are correspond with a good outcome. | Baseline through 12 hours post initiation of dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fraction of Inspired Oxygen (FiO2) | Change from baseline in FiO2 measured using mean and standard deviation. FiO2 level, ranging from 0.21 (room air) to 1.00 (i.e., 21% to 100%) | Baseline through 24 hours post initiation of dosing | 
| Partial Pressure of Oxygen (PaO2) | Change from baseline in PaO2 measured using mean and standard deviation | Baseline through 24 hours post initiation of dosing | 
| Oxygenation From Pulse Oximetry (SpO2) | Change from baseline in SpO2 measured using mean and standard deviation | Baseline through 24 hours post initiation of dosing | 
| Oxygen Index (OI) | Change from baseline in OI. OI is an index value, calculated as Paw x FiO2 x 100 / PaO2, measured using mean and standard deviation. It is a calculation that measures the fraction of inspired oxygen and its usage within the body, and a lower value is better. Values can range from 0 to 1000; values under 25 are correspond with a good outcome. | Baseline through 24 hours post initiation of dosing | 
| Partial Pressure of Carbon Dioxide (PaCO2) | Change from baseline in PaCO2 measured using mean and standard deviation | Baseline through 24 hours post initiation of dosing | 
| End Tidal Carbon Dioxide (ETCO2) | Change from baseline in ETCO2 measured using mean and standard deviation | Baseline through 24 hours post initiation of dosing | 
| PaO2 to FiO2 (P/F) Ratio | Change from baseline in ratio of arterial oxygen concentration to fraction of inspired oxygen (P/F ratio) and/or ratio of pulse oximetric saturation to fraction of inspired oxygen (P/F and/or S/F ratios) measured using mean and standard deviation. | Baseline through 24 hours post initiation of dosing | 
| SpO2 to FiO2 (S/F) Ratio | Change from baseline in ratio of pulse oximetric saturation to fraction of inspired oxygen (S/F ratio) measured using mean and standard deviation. | Through 24 hours | 
| Plateau Pressure (PPLAT) | Change from baseline in PPLAT, as measured on the ventilator, measured using mean and standard deviation. | Through 24 Hours | 
| Peak Inspiratory Pressure (PIP) | Change from baseline in PIP, as measured on the ventilator, measured using mean and standard deviation. | Baseline through 24 hours post initiation of dosing | 
| Peak Expiratory End Pressure (PEEP) | Change from baseline in PEEP, measured using mean and standard deviation. | Through 24 hours | 
| Ventilation Index (VI) | Change from baseline in VI, defined as (Respiration Rate [RR]) × (Peak Inspiratory Pressure [PIP] - Positive End Expiratory Pressure [PEEP]) × (Partial Pressure of Arterial Carbon Dioxide (PaCO2)] / (1000), measured using mean and standard deviation. The VI is used to determine the severity of respiratory illness, with higher values indicating worsening respiratory illness. | Baseline through 24 hours post initiation of dosing | 
| Lung Compliance (CL) | Change from baseline in lung compliance measured using measured using mean and standard deviation. | Baseline through 24 hours post initiation of dosing | 
| Daily Lung Compliance (Static) on Ventilator | Change from baseline in daily lung compliance (static) on ventilator using measured using mean and standard deviation. | Baseline through 24 hours post initiation of dosing | 
| Ventilator Free Days | Ventilator free days measured using mean and standard deviation. | Baseline through 30 days post initiation of dosing | 
| Days in the Intensive Care Unit (ICU) | Days in the intensive care unit (ICU) measured using mean and standard deviation. | Baseline through 30 days post initiation of dosing | 
| Days in the Hospital | Days in the hospital measured using mean and standard deviation. | Baseline through 30 days post initiation of dosing | 
| All-cause Mortality | Number of participant deaths. | Baseline through 30 days post initiation of dosing | 
| Organ Failure Free Days | Organ failure free days measured using mean and standard deviation. | Baseline through 30 days post initiation of dosing |