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

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.

Study Overview

• Status: Completed
• Conditions: COVID-19; Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS)
• Intervention / Treatment: Drug: Lucinactant

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina
    • CEMIC - Centro de Educacion Medica e Investigaciones Clinicals
  • Buenos Aires, Argentina, C1118
    • Fundacion Sanatorio Güemes
  • Buenos Aires, Argentina, C1118
    • Hospital Aleman
  • Buenos Aires, Argentina, C119ABB
    • Hospital Italiano de Bueno Aires
• United States
  • California
    • La Jolla, California, United States, 92037
      • University California San Diego - Jacobs Medical Center
    • San Diego, California, United States, 92103
      • University of California San Diego - Medical Center, Hillcrest
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Augusta University Health
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Windtree Therapeutics
• Investigators: Principal Investigator: Yuh-Chin T Huang, MD, MHS, Duke University; Study Director: Steve G Simonson, MD, Windtree Therapeutics

Publications and helpful links

General Publications

• Lee CK, Merriam LT, Pearson JC, Lipnick MS, McKleroy W, Kim EY. Treating COVID-19: Evolving approaches to evidence in a pandemic. Cell Rep Med. 2022 Feb 9;3(3):100533. doi: 10.1016/j.xcrm.2022.100533. eCollection 2022 Mar 15.
• Cohen CL, Walker KH, Hsiang M, Sonenthal PD, Riviello ED, Rouhani SA, Lipnick MS, Merriam LT, Kim EY. Combating information chaos: a case for collaborative clinical guidelines in a pandemic. Cell Rep Med. 2021 Aug 17;2(8):100375. doi: 10.1016/j.xcrm.2021.100375. Epub 2021 Jul 27.

Study record dates

Study Major Dates

• Study Start (Actual): January 5, 2021
• Primary Completion (Actual): February 20, 2022
• Study Completion (Actual): February 20, 2022

Study Registration Dates

• First Submitted: May 13, 2020
• First Submitted That Met QC Criteria: May 13, 2020
• First Posted (Actual): May 15, 2020

Study Record Updates

• Last Update Posted (Actual): June 23, 2023
• Last Update Submitted That Met QC Criteria: June 22, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Respiration Disorders; Pneumonia, Viral; Pneumonia; Lung Diseases; Wounds and Injuries; Infant, Newborn, Diseases; Infant, Premature, Diseases; Thoracic Injuries; COVID-19; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Lung Injury; Respiratory System Agents; Pulmonary Surfactants
• Other Study ID Numbers: 02-CL-2001a

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

The preparation and submittal for publication of a manuscript containing the study results shall be in accordance with a process determined by a mutual written agreement among Windtree and participating institutions.

The publication or presentation of any study results shall comply with all applicable privacy laws, including but not limited to HIPAA. This trial will be registered at ClinicalTrials.gov, and results information from this trial will be submitted. In addition, every attempt will be made to publish results in peer-reviewed journals.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No