A Study to Assess Efficacy and Safety of RESP301 Plus Standard of Care (SOC) Compared to SOC Alone in Hospitalized Participants With COVID-19

A modified WHO ordinal scale was used for consistency with the recent study in adults hospitalized with severe COVID-19, to record the participant's status at the time of assessment. The modified WHO ordinal scale included the following levels :

1= Not hospitalized, no limitations on activities; 2= Not hospitalized, limitation on activities; 3= Hospitalized, not requiring supplemental oxygen; 4= Hospitalized, requiring supplemental oxygen; 5= Hospitalized, on non-invasive ventilation or high-flow oxygen devices; 6= Hospitalized, on invasive mechanical ventilation or extra corporeal membrane oxygenation (ECMO); 7= Death. Higher scores mean worse outcome. The number of participants that had an increase in at least one level higher score on the modified WHO ordinal scale was assessed.

Pulse oximetry measurements were performed to evaluate SpO2. The effect of RESP301 as measured by room air SpO2 was assessed.

The NEWS is based on a simple aggregate scoring system in which a score is allocated to physiological measurements, already recorded in routine practice, when patients present to, or are being monitored in hospital. Six simple physiological parameters form the basis of the scoring system: 1. Respiration rate; 2. Oxygen saturation; 3. Systolic blood pressure; 4. Pulse rate; 5. Level of consciousness or new confusion; 6. Temperature.

Each score is 0-3 and individual scores are added together for an overall score. An additional two points are added if the patient is receiving oxygen therapy. The total possible score ranges from 0 to 20. The higher the score the greater the clinical risk. Higher scores indicate the need for escalation, medical review and possible clinical intervention, and more intensive monitoring.

A modified WHO ordinal scale was used for consistency with the recent study in adults hospitalized with severe COVID-19, to record the participant's status at the time of assessment. The modified WHO ordinal scale included the following levels :

1= Not hospitalized, no limitations on activities; 2= Not hospitalized, limitation on activities; 3= Hospitalized, not requiring supplemental oxygen; 4= Hospitalized, requiring supplemental oxygen; 5= Hospitalized, on non-invasive ventilation or high-flow oxygen devices; 6= Hospitalized, on invasive mechanical ventilation or extra corporeal membrane oxygenation (ECMO); 7= Death. Higher scores mean worse outcome. Change from baseline for Number of Participants on the modified WHO ordinal scale was assesed.

Time to improvement is the time in which the participant sees a decrease after first study treatment in the WHO 7-point ordinal scale from baseline to a value at least one level lower in days (date of decrease in WHO scale - first dose date + 1). In the case that a patient has not decreased in the WHO scale at time of analysis or withdraws from the study before leaving the hospital, they would be censored at their date of last assessment in the data cut or early discontinuation date, respectively.

Time to progression is the time in which the patient sees an increase after first study treatment in the WHO 7-point ordinal scale from baseline to a value at least one level higher in days (date of increase in WHO scale - first dose date + 1). In the case that a patient has not increased in the WHO scale at time of analysis or withdraws from the study before leaving the hospital, they would be censored at their date of last assessment in the data cut or early discontinuation date, respectively.

AEs (non-serious) as variables of safety and tolerability of RESP301 were assessed.

Severe AEs is defined as an event that prevents normal everyday activities. An AE that is assessed as severe should not be confused with an SAE. Severe is a category utilized for rating the intensity of an event; and both AE and SAE can be assessed as severe.

Time to hospital discharge is the time in the hospital after first study treatment in days (date of discharge - first dose date + 1). Patients who die before leaving the hospital would be considered failures (did not achieve hospital discharge) and censored. In the case that a patient is still hospitalized at time of analysis or withdraws from the study before leaving the hospital, they would be censored at their date of last assessment in the data cut or early discontinuation date, respectively.

Incidence of mortality by Day 28 is the number of participants who have died by Day 28 and the percentage of patients reaching this endpoint will be summarized by treatment group.

Room Air SpO2 for a summary of participants with reduction to < 90%, unless well clinically tolerated according to Investigator's opinion was assesed.

Incidence of clinical bronchial hyper responsiveness related to nebulization was assessed. Oxygen saturation decreased and wheezing was assessed as an incidence of clinical bronchial hyper-responsiveness related to nebulization, requiring temporal increase of supplemental oxygen.