A Study of GEn-1124 in Subjects With Acute Respiratory Distress Syndrome (ARDS)

• Incidence (frequency over time) of serious adverse events (SAEs) unexpected in ARDS patients.
• Incidence (frequency over time) of treatment-emergent adverse events (TEAE).

Oxygenation Index is calculated as PAW × FiO2 × 100 / SpO2 where PAW is product of mean airway pressure (PAW), FiO2 is fraction of inspired oxygen, and SpO2 is pulse oxygen saturation (as long as the lowest SpO2 measurement for the day was < 97%).

Ratio of arterial oxygen partial pressure to fractional inspired oxygen is calculated as PaO2 / FiO2 where PaO2 indicates arterial oxygen partial pressure and FiO2 indicates fraction of inspired oxygen. All values are derived from ventilator parameters and arterial blood gas.

Static compliance is calculated as the tidal volume divided by the difference between airway plateau pressure and end-expiratory pressure (Pplat - PEEP) where Plat is airway plateau pressure and PEEP is positive end-expiratory pressure. All values are derived from ventilator parameters.

Dynamic compliance is calculated as the tidal volume divided by the difference between peak inspiratory pressure and end-expiratory pressure (PIP - PEEP) where Plat is airway plateau pressure and PEEP is positive end-expiratory pressure. All values are derived from ventilator parameters.

To calculate RALE, each radiographic quadrant is scored for extent of consolidation (0-4) and density of opacification (1-3). The product of the consolidation and density scores for each of the four quadrants is summed (minimum score=0, maximum score=48; higher scores mean worse outcome).

Duration of invasive mechanical ventilation is defined as the number of hours that the subject receives invasive mechanical ventilation for at least 1 hour duration.

Duration of ventilatory support is defined as the number of hours that the subject receives any ventilation support for at least 1 hour duration.

VFDs to day 28 are defined as the number of days from the time of initiating unassisted breathing to day 28 after randomization, assuming survival for at least 48 hours after initiating unassisted breathing and continued unassisted breathing to day 28. If a subject returns to assisted breathing and subsequently achieves unassisted breathing to day 28, VFDs will be counted from the end of the last period of assisted breathing to day 28. A period of assisted breathing lasting less than 24 hours and for the purpose of a surgical procedure will not count against the VFD calculation. If a subject was receiving assisted breathing at day 27 or dies prior to day 28, VFDs will be zero. Subjects transferred to another hospital or other health care facility will be followed to day 28 to assess this endpoint.

Intubation is defined as the need for initial intubation in subjects who are not intubated at baseline.

Reintubation is defined as the need for reintubation after initial successful extubation for 48 hours.

The SOFA score is used for prediction of mortality in ICU patients. Initial and highest scores of more than 11 or mean scores of more than 5 corresponded to mortality of more than 80%.

Hospital mortality is defined as mortality that occurred during hospitalization up to Day 28, defined as 672 hours from the time of randomization. All subjects will be classified as either "alive at Study Day 28" or, if dead, "dead at Study Day 28."

All-cause mortality is defined that occurred for any cause up to Day 28, defined as 672 hours from the time of randomization. All subjects will be classified as either "alive at Study Day 28" or, if dead, "dead at Study Day 28."

Length of ICU stay is defined as the number of hours in the ICU for at least 1 hour duration.

Length of hospital stay will be defined as the number of hours hospitalized for at least 1 hour duration.

Alive and free of respiratory failure is defined as being alive without the need for invasive mechanical ventilation, non-invasive ventilation, high-flow nasal cannula (heated, humidified, oxygen delivered via reinforced nasal cannula at flow rates >20 L/min with fraction of delivered oxygen ≥ 0.5), or extracorporeal membrane oxygenation (ECMO).

To compute AVF, each subject is compared to every other subject in both trial arms and assigned a score (win=+1; lose=-1; tie=0) for each pairwise comparison, based on which fared better.

Length of time is defined as the number of hour to recover gas exchange to PaO2/FiO2 ³ 300 for at least 24 hours.

The short form 36 health survey questionnaire (SF-36)18 measures health perception. The lowest score of 0 indicates unhealthy, where as the highest score of 100 indicates healthy.

The EuroQOL health survey instrument (EQ-5D-5L)18 is a five-dimensional five-level generic measure designed to measure and value health status. A Level 1 score indicates no problems. A Level 5 score indicates unable to/extreme problems.

Protein biomarkers including TNFalpha, IL6 and IL1beta, IL10 and HSP27 will be measured by Olink's arbitrary unit, Normalized Protein eXpression (NPX), which is in Log2 scale.

Protein biomarkers including TNFalpha, IL6 and IL1beta, IL10 and HSP27 will be measured by Olink's arbitrary unit, Normalized Protein eXpression (NPX), which is in Log2 scale.

Protein biomarkers including TNFalpha, IL6 and IL1beta, IL10 and HSP27 will be measured by Olink's arbitrary unit, Normalized Protein eXpression (NPX), which is in Log2 scale.