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

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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04389671

Enrollment

Registered

2020-05-15

Start date

2021-01-05

Completion date

2022-02-20

Last updated

2023-06-23

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

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

Brief summary

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

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.

Interventions

DRUGLucinactant

Lucinactant administered as a liquid at a dose of 80 mg total phospholipids (TPL)/kg lean body weight delivered

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Intervention model description

Open-label, single treatment of reconstituted Lucinactant, delivered as an intratracheal liquid.

Eligibility

Sex/Gender

ALL

Age

18 Years to 75 Years

Healthy volunteers

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: 1. Acute coronary syndromes or active ischemic heart disease (as assessed by the PI using troponin and ECG) 2. Cardiac ejection fraction \< 40% (if known); 3. Need for multiple-dose vasopressors to support blood pressure (single dose vasopressors, such as Levophed™ ≤ 0.1 mcg/kg/min are allowed); 4. Cardiogenic pulmonary edema as the etiology of the current respiratory distress; 5. 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.

Design outcomes

Primary

Measure	Time frame	Description
Oxygen Index (OI)	Baseline through 12 hours post initiation of dosing	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.

Secondary

Measure	Time frame	Description
Partial Pressure of Oxygen (PaO2)	Baseline through 24 hours post initiation of dosing	Change from baseline in PaO2 measured using mean and standard deviation
Oxygenation From Pulse Oximetry (SpO2)	Baseline through 24 hours post initiation of dosing	Change from baseline in SpO2 measured using mean and standard deviation
Oxygen Index (OI)	Baseline through 24 hours post initiation of dosing	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.
Partial Pressure of Carbon Dioxide (PaCO2)	Baseline through 24 hours post initiation of dosing	Change from baseline in PaCO2 measured using mean and standard deviation
End Tidal Carbon Dioxide (ETCO2)	Baseline through 24 hours post initiation of dosing	Change from baseline in ETCO2 measured using mean and standard deviation
PaO2 to FiO2 (P/F) Ratio	Baseline through 24 hours post initiation of dosing	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.
SpO2 to FiO2 (S/F) Ratio	Through 24 hours	Change from baseline in ratio of pulse oximetric saturation to fraction of inspired oxygen (S/F ratio) measured using mean and standard deviation.
Plateau Pressure (PPLAT)	Through 24 Hours	Change from baseline in PPLAT, as measured on the ventilator, measured using mean and standard deviation.
Peak Inspiratory Pressure (PIP)	Baseline through 24 hours post initiation of dosing	Change from baseline in PIP, as measured on the ventilator, measured using mean and standard deviation.
Fraction of Inspired Oxygen (FiO2)	Baseline through 24 hours post initiation of dosing	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%)
Ventilation Index (VI)	Baseline through 24 hours post initiation of dosing	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.
Lung Compliance (CL)	Baseline through 24 hours post initiation of dosing	Change from baseline in lung compliance measured using measured using mean and standard deviation.
Daily Lung Compliance (Static) on Ventilator	Baseline through 24 hours post initiation of dosing	Change from baseline in daily lung compliance (static) on ventilator using measured using mean and standard deviation.
Ventilator Free Days	Baseline through 30 days post initiation of dosing	Ventilator free days measured using mean and standard deviation.
Days in the Intensive Care Unit (ICU)	Baseline through 30 days post initiation of dosing	Days in the intensive care unit (ICU) measured using mean and standard deviation.
Days in the Hospital	Baseline through 30 days post initiation of dosing	Days in the hospital measured using mean and standard deviation.
All-cause Mortality	Baseline through 30 days post initiation of dosing	Number of participant deaths.
Organ Failure Free Days	Baseline through 30 days post initiation of dosing	Organ failure free days measured using mean and standard deviation.
Peak Expiratory End Pressure (PEEP)	Through 24 hours	Change from baseline in PEEP, measured using mean and standard deviation.

Countries

Argentina, United States

Participant flow

Recruitment details

First participant enrolled: 05 January 2021 Last participant completed: 20 February 2022 Enrollment occurred in hospital

Pre-assignment details

No wash-out or run-in

Participants by arm

Arm	Count
Lyophilized Lucinactant Lyophilized Lucinactant reconstituted with sterile water for injection Lucinactant: Lucinactant administered as a liquid at a dose of 80 mg total phospholipids (TPL)/kg lean body weight delivered	19
Total	19

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Death	7

Baseline characteristics

Characteristic	Lyophilized Lucinactant
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	2 Participants
Age, Categorical Between 18 and 65 years	17 Participants
Age, Continuous	47.5 years STANDARD_DEVIATION 13.69
Ethnicity (NIH/OMB) Hispanic or Latino	7 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	12 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Oxygen Index	10.7 index STANDARD_DEVIATION 6.17
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	0 Participants
Race (NIH/OMB) Black or African American	5 Participants
Race (NIH/OMB) More than one race	2 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants
Race (NIH/OMB) White	11 Participants
Region of Enrollment Argentina	2 participants
Region of Enrollment United States	17 participants
Sex: Female, Male Female	4 Participants
Sex: Female, Male Male	15 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	7 / 19
other Total, other adverse events	16 / 19
serious Total, serious adverse events	8 / 19

Outcome results

Primary

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.

Time frame: Baseline through 12 hours post initiation of dosing