COVID-19
Conditions
Brief summary
The effect of RESP301 as an add on treatment to SOC will be evaluated for its efficacy in reducing rate of progression to a more severe level of COVID-19 and for safety, by comparison with SOC alone in hospitalized COVID-19 patients.
Detailed description
This is an open-label, randomized, multicenter, parallel group, concurrent, controlled study using a sequential adaptive design to evaluate the efficacy and safety of RESP301 plus SOC versus SOC alone in hospitalized patients with COVID-19 (World Health Organization \[WHO\] ordinal scale level 3 or 4). Approximately 300 participants will be enrolled and randomized 2:1 to the Investigational arm or the Control arm. The study will be divided into the following periods: Screening period: (up to 2 days), Intervention (up to 10 days), follow-up (Day 14 and Day 28).
Interventions
DRUGRESP301, a Nitric Oxide generating solution
Product application requires inhalation using a standard handheld nebulizer.
OTHERStandard of Care
Participants will receive institutional SOC for the treatment of COVID-19.
Sponsors
Thirty Respiratory Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Participant has laboratory-confirmed SARS-CoV-2 infection as determined by reverse transcriptase polymerase chain reaction (RT-PCR) or other approved clinical testing prior to randomization. 2. Participant is hospitalized in relation to COVID-19, requiring supplemental oxygen to maintain SpO2 at a safe level (WHO level 3 & 4). 3. Participant is capable of giving signed informed consent 4. Participant is male or female. All females of childbearing potential, including pregnant females, must consent to urine pregnancy testing at screening to be eligible for the study.
Exclusion criteria
1. Rapidly deteriorating or likely to require escalation to high flow oxygen, invasive or non-invasive ventilatory support within 24 hours according to Investigator's opinion. 2. Unable to safely receive a nebulized treatment for approximately 8 minutes according to Investigator's opinion. 3. Unable to receive or considered ineligible for invasive or non-invasive ventilatory support. 4. History of methemoglobinemia. 5. Presence of uncontrolled asthma, history of severe bronchospasm. 6. Presence of severe chronic respiratory disease and tracheostomy. 7. Suspected or confirmed untreated, active tuberculosis. 8. Severely immune-compromised participants in Investigator's opinion. 9. Recent active coronary artery disease or decompensated heart failure.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Progress by at Least One Level Higher on the Modified WHO Ordinal Scale | Baseline, Day 2 and Day 3 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in National Early Warning Score (NEWS) 2 Symptom Score From Baseline Over Time | Day 1 (Baseline), Day 2, 3, 4, 5, 6, and 7 | 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. |
| Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 1 (Baseline), Day 2, 3, 4, 5, 6, and 7 | 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 of at Least One Level Lower on the Modified WHO Ordinal Scale | From Baseline to Day 28 | 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 of at Least One Level Higher on the Modified WHO Ordinal Scale | From Baseline to Day 28 | 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. |
| Change in Room Air Oxygen Saturation (SpO2) From Baseline Over Time | Day 1 (Baseline) Post-Nebulization, Day 2, 3, 4, 5, 6, and 7 | Pulse oximetry measurements were performed to evaluate SpO2. The effect of RESP301 as measured by room air SpO2 was assessed. |
| Time to Hospital Discharge | Day 10 | 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. |
| Number of Participants With Mortality by Day 28 | Day 28 | 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. |
| Reduction in Oxygen Saturation (SpO2) to <90% | Day 1 (Baseline), Day 2, Day 3 | Room Air SpO2 for a summary of participants with reduction to \< 90%, unless well clinically tolerated according to Investigator's opinion was assesed. |
| Events of Clinical Bronchial Hyper Responsiveness Related to Nebulization | From screening to safety follow up (Day 28) | 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. |
| Number of Participants With Adverse Events | From screening to safety follow up (Day 28) | 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. |
Countries
United Kingdom
Participant flow
Recruitment details
The study was conducted at 2 centers that enrolled 19 participants in the United Kingdom (UK) from 29-Jul-2020 (First Enrolment) to 21-May-2021 (Last Participant Completed).
Pre-assignment details
The screening period was of 2 days. All the study assessments were performed as per the schedule of assessment.
Participants by arm
| Arm | Count |
|---|---|
| RESP301+SoC Participants received inhaled RESP301 administered using a nebulizer three times a day (TID) for up to 10 days in addition to the standard of care (SoC). | 14 |
| Standard of Care (SoC) Participants received institutional SOC alone for the treatment of COVID-19. | 5 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 3 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | RESP301+SoC | Standard of Care (SoC) | Total |
|---|---|---|---|
| Age, Customized <65 years | 11 Participants | 4 Participants | 15 Participants |
| Age, Customized >=65 years | 3 Participants | 1 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants | 4 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 2 Participants | 8 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 3 Participants | 9 Participants |
| Sex: Female, Male Female | 7 Participants | 2 Participants | 9 Participants |
| Sex: Female, Male Male | 7 Participants | 3 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 5 |
| other Total, other adverse events | 10 / 14 | 2 / 5 |
| serious Total, serious adverse events | 0 / 14 | 0 / 5 |
Outcome results
Primary
Number of Participants Who Progress by at Least One Level Higher on the Modified WHO Ordinal Scale
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.
Time frame: Baseline, Day 2 and Day 3
Population: The intent-to-treat (ITT) population included all randomized participants. For RESP301+SoC arm only 1 participant was available for this analysis who had an increase in at least one level higher score on the modified WHO ordinal scale.~For SoC arm, no data were collected. Hence, 0 participants were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| RESP301+SoC | Number of Participants Who Progress by at Least One Level Higher on the Modified WHO Ordinal Scale | Baseline : WHO 7-point ordinal scale: 4 | 1 Participants |
| RESP301+SoC | Number of Participants Who Progress by at Least One Level Higher on the Modified WHO Ordinal Scale | Baseline : WHO 7-point ordinal scale: 2 | 0 Participants |
| RESP301+SoC | Number of Participants Who Progress by at Least One Level Higher on the Modified WHO Ordinal Scale | Day 2 : WHO 7-point ordinal scale: 7 | 0 Participants |
| RESP301+SoC | Number of Participants Who Progress by at Least One Level Higher on the Modified WHO Ordinal Scale | Day 3 : WHO 7-point ordinal scale: 1 | 0 Participants |
| RESP301+SoC | Number of Participants Who Progress by at Least One Level Higher on the Modified WHO Ordinal Scale | Day 3 : WHO 7-point ordinal scale: 3 | 0 Participants |
| RESP301+SoC | Number of Participants Who Progress by at Least One Level Higher on the Modified WHO Ordinal Scale | Baseline : WHO 7-point ordinal scale: 1 | 0 Participants |
| RESP301+SoC | Number of Participants Who Progress by at Least One Level Higher on the Modified WHO Ordinal Scale | Baseline : WHO 7-point ordinal scale: 3 | 0 Participants |
| RESP301+SoC | Number of Participants Who Progress by at Least One Level Higher on the Modified WHO Ordinal Scale | Baseline : WHO 7-point ordinal scale: 5 | 0 Participants |
| RESP301+SoC | Number of Participants Who Progress by at Least One Level Higher on the Modified WHO Ordinal Scale | Baseline : WHO 7-point ordinal scale: 6 | 0 Participants |
| RESP301+SoC | Number of Participants Who Progress by at Least One Level Higher on the Modified WHO Ordinal Scale | Baseline : WHO 7-point ordinal scale: 7 | 0 Participants |
| RESP301+SoC | Number of Participants Who Progress by at Least One Level Higher on the Modified WHO Ordinal Scale | Day 2 : WHO 7-point ordinal scale: 1 | 0 Participants |
| RESP301+SoC | Number of Participants Who Progress by at Least One Level Higher on the Modified WHO Ordinal Scale | Day 2 : WHO 7-point ordinal scale: 2 | 0 Participants |
| RESP301+SoC | Number of Participants Who Progress by at Least One Level Higher on the Modified WHO Ordinal Scale | Day 2 : WHO 7-point ordinal scale: 3 | 0 Participants |
| RESP301+SoC | Number of Participants Who Progress by at Least One Level Higher on the Modified WHO Ordinal Scale | Day 2 : WHO 7-point ordinal scale: 4 | 1 Participants |
| RESP301+SoC | Number of Participants Who Progress by at Least One Level Higher on the Modified WHO Ordinal Scale | Day 2 : WHO 7-point ordinal scale: 5 | 0 Participants |
| RESP301+SoC | Number of Participants Who Progress by at Least One Level Higher on the Modified WHO Ordinal Scale | Day 2 : WHO 7-point ordinal scale: 6 | 0 Participants |
| RESP301+SoC | Number of Participants Who Progress by at Least One Level Higher on the Modified WHO Ordinal Scale | Day 3 : WHO 7-point ordinal scale: 2 | 0 Participants |
| RESP301+SoC | Number of Participants Who Progress by at Least One Level Higher on the Modified WHO Ordinal Scale | Day 3 : WHO 7-point ordinal scale: 4 | 0 Participants |
| RESP301+SoC | Number of Participants Who Progress by at Least One Level Higher on the Modified WHO Ordinal Scale | Day 3 : WHO 7-point ordinal scale: 5 | 1 Participants |
| RESP301+SoC | Number of Participants Who Progress by at Least One Level Higher on the Modified WHO Ordinal Scale | Day 3 : WHO 7-point ordinal scale: 6 | 0 Participants |
| RESP301+SoC | Number of Participants Who Progress by at Least One Level Higher on the Modified WHO Ordinal Scale | Day 3 : WHO 7-point ordinal scale: 7 | 0 Participants |
| Standard of Care (SoC) | Number of Participants Who Progress by at Least One Level Higher on the Modified WHO Ordinal Scale | Day 2 : WHO 7-point ordinal scale: 2 | 0 Participants |
| Standard of Care (SoC) | Number of Participants Who Progress by at Least One Level Higher on the Modified WHO Ordinal Scale | Day 3 : WHO 7-point ordinal scale: 3 | 0 Participants |
| Standard of Care (SoC) | Number of Participants Who Progress by at Least One Level Higher on the Modified WHO Ordinal Scale | Day 2 : WHO 7-point ordinal scale: 3 | 0 Participants |
| Standard of Care (SoC) | Number of Participants Who Progress by at Least One Level Higher on the Modified WHO Ordinal Scale | Day 3 : WHO 7-point ordinal scale: 7 | 0 Participants |
| Standard of Care (SoC) | Number of Participants Who Progress by at Least One Level Higher on the Modified WHO Ordinal Scale | Day 3 : WHO 7-point ordinal scale: 2 | 0 Participants |
| Standard of Care (SoC) | Number of Participants Who Progress by at Least One Level Higher on the Modified WHO Ordinal Scale | Day 2 : WHO 7-point ordinal scale: 4 | 0 Participants |
| Standard of Care (SoC) | Number of Participants Who Progress by at Least One Level Higher on the Modified WHO Ordinal Scale | Day 3 : WHO 7-point ordinal scale: 4 | 0 Participants |
| Standard of Care (SoC) | Number of Participants Who Progress by at Least One Level Higher on the Modified WHO Ordinal Scale | Baseline : WHO 7-point ordinal scale: 2 | 0 Participants |
| Standard of Care (SoC) | Number of Participants Who Progress by at Least One Level Higher on the Modified WHO Ordinal Scale | Day 2 : WHO 7-point ordinal scale: 5 | 0 Participants |
| Standard of Care (SoC) | Number of Participants Who Progress by at Least One Level Higher on the Modified WHO Ordinal Scale | Baseline : WHO 7-point ordinal scale: 3 | 0 Participants |
| Standard of Care (SoC) | Number of Participants Who Progress by at Least One Level Higher on the Modified WHO Ordinal Scale | Baseline : WHO 7-point ordinal scale: 1 | 0 Participants |
| Standard of Care (SoC) | Number of Participants Who Progress by at Least One Level Higher on the Modified WHO Ordinal Scale | Baseline : WHO 7-point ordinal scale: 4 | 0 Participants |
| Standard of Care (SoC) | Number of Participants Who Progress by at Least One Level Higher on the Modified WHO Ordinal Scale | Day 3 : WHO 7-point ordinal scale: 6 | 0 Participants |
| Standard of Care (SoC) | Number of Participants Who Progress by at Least One Level Higher on the Modified WHO Ordinal Scale | Baseline : WHO 7-point ordinal scale: 5 | 0 Participants |
| Standard of Care (SoC) | Number of Participants Who Progress by at Least One Level Higher on the Modified WHO Ordinal Scale | Day 2 : WHO 7-point ordinal scale: 6 | 0 Participants |
| Standard of Care (SoC) | Number of Participants Who Progress by at Least One Level Higher on the Modified WHO Ordinal Scale | Baseline : WHO 7-point ordinal scale: 6 | 0 Participants |
| Standard of Care (SoC) | Number of Participants Who Progress by at Least One Level Higher on the Modified WHO Ordinal Scale | Day 2 : WHO 7-point ordinal scale: 7 | 0 Participants |
| Standard of Care (SoC) | Number of Participants Who Progress by at Least One Level Higher on the Modified WHO Ordinal Scale | Baseline : WHO 7-point ordinal scale: 7 | 0 Participants |
| Standard of Care (SoC) | Number of Participants Who Progress by at Least One Level Higher on the Modified WHO Ordinal Scale | Day 3 : WHO 7-point ordinal scale: 1 | 0 Participants |
| Standard of Care (SoC) | Number of Participants Who Progress by at Least One Level Higher on the Modified WHO Ordinal Scale | Day 2 : WHO 7-point ordinal scale: 1 | 0 Participants |
| Standard of Care (SoC) | Number of Participants Who Progress by at Least One Level Higher on the Modified WHO Ordinal Scale | Day 3 : WHO 7-point ordinal scale: 5 | 0 Participants |
Secondary
Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit
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 frame: Day 1 (Baseline), Day 2, 3, 4, 5, 6, and 7
Population: The intent-to-treat (ITT) population included all randomized participants.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| RESP301+SoC | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 3: change from baseline: Modified WHO 7-point ordinal scale 1 | 1 Participants |
| RESP301+SoC | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 2: change from baseline: Modified WHO 7-point ordinal scale 0 | 8 Participants |
| RESP301+SoC | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 2: change from baseline: Modified WHO 7-point ordinal scale 2 | 0 Participants |
| RESP301+SoC | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 2: change from baseline: Modified WHO 7-point ordinal scale -3 | 0 Participants |
| RESP301+SoC | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 2: change from baseline: Modified WHO 7-point ordinal scale -2 | 0 Participants |
| RESP301+SoC | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 2: change from baseline: Modified WHO 7-point ordinal scale -1 | 4 Participants |
| RESP301+SoC | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 2: change from baseline: Modified WHO 7-point ordinal scale 1 | 0 Participants |
| RESP301+SoC | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 2: change from baseline: Modified WHO 7-point ordinal scale 3 | 0 Participants |
| RESP301+SoC | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 2: change from baseline: Modified WHO 7-point ordinal scale 4 | 0 Participants |
| RESP301+SoC | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 3: change from baseline: Modified WHO 7-point ordinal scale -3 | 0 Participants |
| RESP301+SoC | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 3: change from baseline: Modified WHO 7-point ordinal scale -2 | 3 Participants |
| RESP301+SoC | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 3: change from baseline: Modified WHO 7-point ordinal scale -1 | 1 Participants |
| RESP301+SoC | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 3: change from baseline: Modified WHO 7-point ordinal scale 0 | 4 Participants |
| RESP301+SoC | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 3: change from baseline: Modified WHO 7-point ordinal scale 2 | 0 Participants |
| RESP301+SoC | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 3: change from baseline: Modified WHO 7-point ordinal scale 3 | 0 Participants |
| RESP301+SoC | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 3: change from baseline: Modified WHO 7-point ordinal scale 4 | 0 Participants |
| RESP301+SoC | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 4: change from baseline: Modified WHO 7-point ordinal scale -3 | 0 Participants |
| RESP301+SoC | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 4: change from baseline: Modified WHO 7-point ordinal scale -2 | 1 Participants |
| RESP301+SoC | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 4: change from baseline: Modified WHO 7-point ordinal scale -1 | 0 Participants |
| RESP301+SoC | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 4: change from baseline: Modified WHO 7-point ordinal scale 0 | 4 Participants |
| RESP301+SoC | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 4: change from baseline: Modified WHO 7-point ordinal scale 1 | 0 Participants |
| RESP301+SoC | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 4: change from baseline: Modified WHO 7-point ordinal scale 2 | 0 Participants |
| RESP301+SoC | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 4: change from baseline: Modified WHO 7-point ordinal scale 3 | 0 Participants |
| RESP301+SoC | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 4: change from baseline: Modified WHO 7-point ordinal scale 4 | 0 Participants |
| RESP301+SoC | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 5: change from baseline: Modified WHO 7-point ordinal scale -3 | 0 Participants |
| RESP301+SoC | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 5: change from baseline: Modified WHO 7-point ordinal scale -2 | 2 Participants |
| RESP301+SoC | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 5: change from baseline: Modified WHO 7-point ordinal scale -1 | 0 Participants |
| RESP301+SoC | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 5: change from baseline: Modified WHO 7-point ordinal scale 0 | 2 Participants |
| RESP301+SoC | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 5: change from baseline: Modified WHO 7-point ordinal scale 1 | 0 Participants |
| RESP301+SoC | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 5: change from baseline: Modified WHO 7-point ordinal scale 2 | 0 Participants |
| RESP301+SoC | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 5: change from baseline: Modified WHO 7-point ordinal scale 3 | 0 Participants |
| RESP301+SoC | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 5: change from baseline: Modified WHO 7-point ordinal scale 4 | 0 Participants |
| RESP301+SoC | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 6: change from baseline: Modified WHO 7-point ordinal scale -3 | 0 Participants |
| RESP301+SoC | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 6: change from baseline: Modified WHO 7-point ordinal scale -2 | 0 Participants |
| RESP301+SoC | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 6: change from baseline: Modified WHO 7-point ordinal scale -1 | 1 Participants |
| RESP301+SoC | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 6: change from baseline: Modified WHO 7-point ordinal scale 0 | 1 Participants |
| RESP301+SoC | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 6: change from baseline: Modified WHO 7-point ordinal scale 1 | 0 Participants |
| RESP301+SoC | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 6: change from baseline: Modified WHO 7-point ordinal scale 2 | 0 Participants |
| RESP301+SoC | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 6: change from baseline: Modified WHO 7-point ordinal scale 3 | 0 Participants |
| RESP301+SoC | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 6: change from baseline: Modified WHO 7-point ordinal scale 4 | 0 Participants |
| RESP301+SoC | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 7: change from baseline: Modified WHO 7-point ordinal scale -3 | 0 Participants |
| RESP301+SoC | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 7: change from baseline: Modified WHO 7-point ordinal scale -2 | 1 Participants |
| RESP301+SoC | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 7: change from baseline: Modified WHO 7-point ordinal scale -1 | 0 Participants |
| RESP301+SoC | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 7: change from baseline: Modified WHO 7-point ordinal scale 0 | 0 Participants |
| RESP301+SoC | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 7: change from baseline: Modified WHO 7-point ordinal scale 1 | 0 Participants |
| RESP301+SoC | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 7: change from baseline: Modified WHO 7-point ordinal scale 2 | 0 Participants |
| RESP301+SoC | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 7: change from baseline: Modified WHO 7-point ordinal scale 3 | 0 Participants |
| RESP301+SoC | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 7: change from baseline: Modified WHO 7-point ordinal scale 4 | 0 Participants |
| Standard of Care (SoC) | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 7: change from baseline: Modified WHO 7-point ordinal scale 3 | 0 Participants |
| Standard of Care (SoC) | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 5: change from baseline: Modified WHO 7-point ordinal scale -3 | 0 Participants |
| Standard of Care (SoC) | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 6: change from baseline: Modified WHO 7-point ordinal scale 1 | 0 Participants |
| Standard of Care (SoC) | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 5: change from baseline: Modified WHO 7-point ordinal scale -2 | 1 Participants |
| Standard of Care (SoC) | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 2: change from baseline: Modified WHO 7-point ordinal scale -3 | 0 Participants |
| Standard of Care (SoC) | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 7: change from baseline: Modified WHO 7-point ordinal scale -1 | 0 Participants |
| Standard of Care (SoC) | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 2: change from baseline: Modified WHO 7-point ordinal scale -2 | 0 Participants |
| Standard of Care (SoC) | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 5: change from baseline: Modified WHO 7-point ordinal scale -1 | 2 Participants |
| Standard of Care (SoC) | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 2: change from baseline: Modified WHO 7-point ordinal scale 0 | 5 Participants |
| Standard of Care (SoC) | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 6: change from baseline: Modified WHO 7-point ordinal scale 2 | 0 Participants |
| Standard of Care (SoC) | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 2: change from baseline: Modified WHO 7-point ordinal scale 1 | 0 Participants |
| Standard of Care (SoC) | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 2: change from baseline: Modified WHO 7-point ordinal scale 2 | 0 Participants |
| Standard of Care (SoC) | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 5: change from baseline: Modified WHO 7-point ordinal scale 0 | 1 Participants |
| Standard of Care (SoC) | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 2: change from baseline: Modified WHO 7-point ordinal scale 3 | 0 Participants |
| Standard of Care (SoC) | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 7: change from baseline: Modified WHO 7-point ordinal scale 2 | 0 Participants |
| Standard of Care (SoC) | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 2: change from baseline: Modified WHO 7-point ordinal scale 4 | 0 Participants |
| Standard of Care (SoC) | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 5: change from baseline: Modified WHO 7-point ordinal scale 1 | 0 Participants |
| Standard of Care (SoC) | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 3: change from baseline: Modified WHO 7-point ordinal scale -3 | 0 Participants |
| Standard of Care (SoC) | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 6: change from baseline: Modified WHO 7-point ordinal scale 3 | 0 Participants |
| Standard of Care (SoC) | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 3: change from baseline: Modified WHO 7-point ordinal scale -2 | 1 Participants |
| Standard of Care (SoC) | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 5: change from baseline: Modified WHO 7-point ordinal scale 2 | 0 Participants |
| Standard of Care (SoC) | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 3: change from baseline: Modified WHO 7-point ordinal scale -1 | 0 Participants |
| Standard of Care (SoC) | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 7: change from baseline: Modified WHO 7-point ordinal scale 0 | 0 Participants |
| Standard of Care (SoC) | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 3: change from baseline: Modified WHO 7-point ordinal scale 0 | 4 Participants |
| Standard of Care (SoC) | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 2: change from baseline: Modified WHO 7-point ordinal scale -1 | 0 Participants |
| Standard of Care (SoC) | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 3: change from baseline: Modified WHO 7-point ordinal scale 1 | 0 Participants |
| Standard of Care (SoC) | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 5: change from baseline: Modified WHO 7-point ordinal scale 3 | 0 Participants |
| Standard of Care (SoC) | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 3: change from baseline: Modified WHO 7-point ordinal scale 2 | 0 Participants |
| Standard of Care (SoC) | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 6: change from baseline: Modified WHO 7-point ordinal scale 4 | 0 Participants |
| Standard of Care (SoC) | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 3: change from baseline: Modified WHO 7-point ordinal scale 3 | 0 Participants |
| Standard of Care (SoC) | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 5: change from baseline: Modified WHO 7-point ordinal scale 4 | 0 Participants |
| Standard of Care (SoC) | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 3: change from baseline: Modified WHO 7-point ordinal scale 4 | 0 Participants |
| Standard of Care (SoC) | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 7: change from baseline: Modified WHO 7-point ordinal scale 4 | 0 Participants |
| Standard of Care (SoC) | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 4: change from baseline: Modified WHO 7-point ordinal scale -3 | 0 Participants |
| Standard of Care (SoC) | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 6: change from baseline: Modified WHO 7-point ordinal scale -3 | 0 Participants |
| Standard of Care (SoC) | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 4: change from baseline: Modified WHO 7-point ordinal scale -2 | 0 Participants |
| Standard of Care (SoC) | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 7: change from baseline: Modified WHO 7-point ordinal scale -3 | 0 Participants |
| Standard of Care (SoC) | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 4: change from baseline: Modified WHO 7-point ordinal scale -1 | 0 Participants |
| Standard of Care (SoC) | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 6: change from baseline: Modified WHO 7-point ordinal scale -2 | 2 Participants |
| Standard of Care (SoC) | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 4: change from baseline: Modified WHO 7-point ordinal scale 0 | 4 Participants |
| Standard of Care (SoC) | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 7: change from baseline: Modified WHO 7-point ordinal scale 1 | 0 Participants |
| Standard of Care (SoC) | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 4: change from baseline: Modified WHO 7-point ordinal scale 1 | 0 Participants |
| Standard of Care (SoC) | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 6: change from baseline: Modified WHO 7-point ordinal scale -1 | 0 Participants |
| Standard of Care (SoC) | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 4: change from baseline: Modified WHO 7-point ordinal scale 2 | 0 Participants |
| Standard of Care (SoC) | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 7: change from baseline: Modified WHO 7-point ordinal scale -2 | 0 Participants |
| Standard of Care (SoC) | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 4: change from baseline: Modified WHO 7-point ordinal scale 3 | 0 Participants |
| Standard of Care (SoC) | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 6: change from baseline: Modified WHO 7-point ordinal scale 0 | 0 Participants |
| Standard of Care (SoC) | Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit | Day 4: change from baseline: Modified WHO 7-point ordinal scale 4 | 0 Participants |
Secondary
Change in National Early Warning Score (NEWS) 2 Symptom Score From Baseline Over Time
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.
Time frame: Day 1 (Baseline), Day 2, 3, 4, 5, 6, and 7
Population: The intent-to-treat (ITT) population included all randomized participants. Here, the number analyzed in each row signifies only the participants who were analyzed for each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RESP301+SoC | Change in National Early Warning Score (NEWS) 2 Symptom Score From Baseline Over Time | Change from Baseline: Day 2 | -0.8 Score on a NEWS scale | Standard Deviation 1.99 |
| RESP301+SoC | Change in National Early Warning Score (NEWS) 2 Symptom Score From Baseline Over Time | Change from Baseline: Day 3 | -1.3 Score on a NEWS scale | Standard Deviation 1.87 |
| RESP301+SoC | Change in National Early Warning Score (NEWS) 2 Symptom Score From Baseline Over Time | Change from Baseline: Day 4 | 1.0 Score on a NEWS scale | Standard Deviation 2.55 |
| RESP301+SoC | Change in National Early Warning Score (NEWS) 2 Symptom Score From Baseline Over Time | Change from Baseline: Day 5 | -2.0 Score on a NEWS scale | Standard Deviation 3.37 |
| RESP301+SoC | Change in National Early Warning Score (NEWS) 2 Symptom Score From Baseline Over Time | Change from Baseline: Day 6 | -1.5 Score on a NEWS scale | Standard Deviation 2.12 |
| RESP301+SoC | Change in National Early Warning Score (NEWS) 2 Symptom Score From Baseline Over Time | Change from Baseline: Day 7 | -1.0 Score on a NEWS scale | Standard Deviation 2.83 |
| Standard of Care (SoC) | Change in National Early Warning Score (NEWS) 2 Symptom Score From Baseline Over Time | Change from Baseline: Day 2 | 1.4 Score on a NEWS scale | Standard Deviation 0.89 |
| Standard of Care (SoC) | Change in National Early Warning Score (NEWS) 2 Symptom Score From Baseline Over Time | Change from Baseline: Day 6 | -2.0 Score on a NEWS scale | Standard Deviation 0 |
| Standard of Care (SoC) | Change in National Early Warning Score (NEWS) 2 Symptom Score From Baseline Over Time | Change from Baseline: Day 3 | -0.2 Score on a NEWS scale | Standard Deviation 1.3 |
| Standard of Care (SoC) | Change in National Early Warning Score (NEWS) 2 Symptom Score From Baseline Over Time | Change from Baseline: Day 5 | -0.5 Score on a NEWS scale | Standard Deviation 3.11 |
| Standard of Care (SoC) | Change in National Early Warning Score (NEWS) 2 Symptom Score From Baseline Over Time | Change from Baseline: Day 4 | 0.5 Score on a NEWS scale | Standard Deviation 0.58 |
Secondary
Change in Room Air Oxygen Saturation (SpO2) From Baseline Over Time
Pulse oximetry measurements were performed to evaluate SpO2. The effect of RESP301 as measured by room air SpO2 was assessed.
Time frame: Day 1 (Baseline) Post-Nebulization, Day 2, 3, 4, 5, 6, and 7
Population: The intent-to-treat (ITT) population included all randomized participants. Here, the number analyzed in each row signified only the participants that were analyzed for each timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RESP301+SoC | Change in Room Air Oxygen Saturation (SpO2) From Baseline Over Time | Day 6 - Change from baseline | -1.0 Percent change | Standard Deviation 1.41 |
| RESP301+SoC | Change in Room Air Oxygen Saturation (SpO2) From Baseline Over Time | Day 7 - Change from baseline | 3.0 Percent change | Standard Deviation 2.83 |
| RESP301+SoC | Change in Room Air Oxygen Saturation (SpO2) From Baseline Over Time | Day 1 - Change from baseline | 0.1 Percent change | Standard Deviation 2.84 |
| RESP301+SoC | Change in Room Air Oxygen Saturation (SpO2) From Baseline Over Time | Day 2 - Change from baseline | -1.7 Percent change | Standard Deviation 4.09 |
| RESP301+SoC | Change in Room Air Oxygen Saturation (SpO2) From Baseline Over Time | Day 3 - Change from baseline | 0.9 Percent change | Standard Deviation 2.8 |
| RESP301+SoC | Change in Room Air Oxygen Saturation (SpO2) From Baseline Over Time | Day 4 - Change from baseline | 1.4 Percent change | Standard Deviation 2.61 |
| RESP301+SoC | Change in Room Air Oxygen Saturation (SpO2) From Baseline Over Time | Day 5 - Change from baseline | 0.3 Percent change | Standard Deviation 1.26 |
| Standard of Care (SoC) | Change in Room Air Oxygen Saturation (SpO2) From Baseline Over Time | Day 3 - Change from baseline | 3.3 Percent change | Standard Deviation 2.08 |
| Standard of Care (SoC) | Change in Room Air Oxygen Saturation (SpO2) From Baseline Over Time | Day 5 - Change from baseline | 4.0 Percent change | Standard Deviation 1 |
| Standard of Care (SoC) | Change in Room Air Oxygen Saturation (SpO2) From Baseline Over Time | Day 1 - Change from baseline | NA Percent change | — |
| Standard of Care (SoC) | Change in Room Air Oxygen Saturation (SpO2) From Baseline Over Time | Day 4 - Change from baseline | 3.0 Percent change | Standard Deviation 2 |
| Standard of Care (SoC) | Change in Room Air Oxygen Saturation (SpO2) From Baseline Over Time | Day 2 - Change from baseline | 1.5 Percent change | Standard Deviation 2.12 |
| Standard of Care (SoC) | Change in Room Air Oxygen Saturation (SpO2) From Baseline Over Time | Day 6 - Change from baseline | 4.5 Percent change | Standard Deviation 3.54 |
Secondary
Events of Clinical Bronchial Hyper Responsiveness Related to Nebulization
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.
Time frame: From screening to safety follow up (Day 28)
Population: The safety analysis set includes the safety (SP) population would include all randomized participants who inhale any amount of study intervention or were randomized to the control arm. The SP would be analyzed according to the actual treatment received. This set will be used for the safety analyses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RESP301+SoC | Events of Clinical Bronchial Hyper Responsiveness Related to Nebulization | 2 Events |
| Standard of Care (SoC) | Events of Clinical Bronchial Hyper Responsiveness Related to Nebulization | 0 Events |
Secondary
Number of Participants With Adverse Events
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 frame: From screening to safety follow up (Day 28)
Population: The safety analysis set includes the safety (SP) population would include all randomized participants who inhale any amount of study intervention or were randomized to the control arm. The SP would be analyzed according to the actual treatment received. This set will be used for the safety analyses.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| RESP301+SoC | Number of Participants With Adverse Events | Participants with at least one AE | 10 Participants |
| RESP301+SoC | Number of Participants With Adverse Events | Participants with at least one AE of Grade 3 or higher | 1 Participants |
| RESP301+SoC | Number of Participants With Adverse Events | Participants with at least one treatment-related AE | 3 Participants |
| RESP301+SoC | Number of Participants With Adverse Events | Participants with at least one severe AE | 1 Participants |
| RESP301+SoC | Number of Participants With Adverse Events | Participants with at least one AE leading to study treatment withdrawal | 3 Participants |
| RESP301+SoC | Number of Participants With Adverse Events | Participants with at least one treatment-related AE leading to study treatment withdrawal | 1 Participants |
| RESP301+SoC | Number of Participants With Adverse Events | Participants with at least one AE leading to dose interruption | 1 Participants |
| RESP301+SoC | Number of Participants With Adverse Events | Participants with at least one treatment-related AE leading to dose interruption | 1 Participants |
| Standard of Care (SoC) | Number of Participants With Adverse Events | Participants with at least one treatment-related AE leading to dose interruption | 0 Participants |
| Standard of Care (SoC) | Number of Participants With Adverse Events | Participants with at least one AE | 2 Participants |
| Standard of Care (SoC) | Number of Participants With Adverse Events | Participants with at least one AE leading to study treatment withdrawal | 0 Participants |
| Standard of Care (SoC) | Number of Participants With Adverse Events | Participants with at least one AE of Grade 3 or higher | 0 Participants |
| Standard of Care (SoC) | Number of Participants With Adverse Events | Participants with at least one AE leading to dose interruption | 0 Participants |
| Standard of Care (SoC) | Number of Participants With Adverse Events | Participants with at least one treatment-related AE | 0 Participants |
| Standard of Care (SoC) | Number of Participants With Adverse Events | Participants with at least one treatment-related AE leading to study treatment withdrawal | 0 Participants |
| Standard of Care (SoC) | Number of Participants With Adverse Events | Participants with at least one severe AE | 0 Participants |
Secondary
Number of Participants With Mortality by Day 28
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.
Time frame: Day 28
Population: The safety analysis set includes the safety (SP) population would include all randomized participants who inhale any amount of study intervention or were randomized to the control arm. The SP would be analyzed according to the actual treatment received. This set will be used for the safety analyses.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| RESP301+SoC | Number of Participants With Mortality by Day 28 | 0 Participants |
| Standard of Care (SoC) | Number of Participants With Mortality by Day 28 | 0 Participants |
Secondary
Reduction in Oxygen Saturation (SpO2) to <90%
Room Air SpO2 for a summary of participants with reduction to \< 90%, unless well clinically tolerated according to Investigator's opinion was assesed.
Time frame: Day 1 (Baseline), Day 2, Day 3
Population: The intent-to-treat (ITT) population included all randomized participants. Here, the number analyzed in each row signified only the participants that were analyzed for each time point.~Standard of Care (SoC) participants did not receive any nebulization. Hence, no participants were analyzed for Pre-nebulization and Post-nebulization. Therefore, no data were available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RESP301+SoC | Reduction in Oxygen Saturation (SpO2) to <90% | Day 1 Pre-Nebulization | 95.0 Percent change | — |
| RESP301+SoC | Reduction in Oxygen Saturation (SpO2) to <90% | Day 1 Post-Nebulization | 93.5 Percent change | Standard Deviation 2.12 |
| RESP301+SoC | Reduction in Oxygen Saturation (SpO2) to <90% | Day 2 Pre-Nebulization | 94.0 Percent change | — |
| RESP301+SoC | Reduction in Oxygen Saturation (SpO2) to <90% | Day 2 Post-Nebulization | 86.0 Percent change | — |
| RESP301+SoC | Reduction in Oxygen Saturation (SpO2) to <90% | Day 3 Pre-Nebulization | 96.0 Percent change | — |
| RESP301+SoC | Reduction in Oxygen Saturation (SpO2) to <90% | Day 3 Post-Nebulization | 94.0 Percent change | — |
Secondary
Time to Hospital Discharge
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.
Time frame: Day 10
Population: The intent-to-treat (ITT) population included all randomized participants. Here, the Overall Number of Participants Analyzed signified only the participants who were discharged from hospital.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| RESP301+SoC | Time to Hospital Discharge | 4.00 Days |
| Standard of Care (SoC) | Time to Hospital Discharge | 6.00 Days |
Secondary
Time to Improvement of at Least One Level Lower on the Modified WHO Ordinal Scale
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 frame: From Baseline to Day 28
Population: The intent-to-treat (ITT) population included all randomized participants. Here, the Overall Number of Participants Analyzed signified only the participants who decrease by at least one level.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| RESP301+SoC | Time to Improvement of at Least One Level Lower on the Modified WHO Ordinal Scale | 4.00 Days |
| Standard of Care (SoC) | Time to Improvement of at Least One Level Lower on the Modified WHO Ordinal Scale | 5.00 Days |
Secondary
Time to Progression of at Least One Level Higher on the Modified WHO Ordinal Scale
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.
Time frame: From Baseline to Day 28
Population: The intent-to-treat (ITT) population included all randomized participants. Here, the Overall Number of Participants Analyzed signified only the participants who increase by at least one level.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| RESP301+SoC | Time to Progression of at Least One Level Higher on the Modified WHO Ordinal Scale | NA Days |