Trial Outcomes & Findings for A Study to Assess Efficacy and Safety of RESP301 Plus Standard of Care (SOC) Compared to SOC Alone in Hospitalized Participants With COVID-19 (NCT NCT04460183)

Last Updated: 2022-06-02

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

19 participants

Primary outcome timeframe

Baseline, Day 2 and Day 3

Results posted on

2022-06-02

Participant Flow

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).

The screening period was of 2 days. All the study assessments were performed as per the schedule of assessment.

Participant milestones

Participant milestones
Measure	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).	Standard of Care (SoC) Participants received institutional SOC alone for the treatment of COVID-19.
Overall Study STARTED	14	5
Overall Study COMPLETED	10	4
Overall Study NOT COMPLETED	4	1

Reasons for withdrawal

Reasons for withdrawal
Measure	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).	Standard of Care (SoC) Participants received institutional SOC alone for the treatment of COVID-19.
Overall Study Lost to Follow-up	3	1
Overall Study Withdrawal by Subject	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	RESP301+SoC n=14 Participants 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).	Standard of Care (SoC) n=5 Participants Participants received institutional SOC alone for the treatment of COVID-19.	Total n=19 Participants Total of all reporting groups
Age, Customized <65 years	11 Participants n=5 Participants	4 Participants n=7 Participants	15 Participants n=5 Participants
Age, Customized >=65 years	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	2 Participants n=7 Participants	9 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	3 Participants n=7 Participants	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	14 Participants n=5 Participants	4 Participants n=7 Participants	18 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	6 Participants n=5 Participants	2 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants	3 Participants n=7 Participants	9 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	RESP301+SoC n=1 Participants 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).	Standard of Care (SoC) Participants received institutional SOC alone for the treatment of COVID-19.
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	0 Participants
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	0 Participants
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	0 Participants
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	0 Participants
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	0 Participants
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	0 Participants
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	0 Participants
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	0 Participants
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	0 Participants
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	0 Participants
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	0 Participants
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	0 Participants
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	0 Participants
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	0 Participants
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	0 Participants
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	0 Participants
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	0 Participants
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	0 Participants
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	0 Participants
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	0 Participants
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	0 Participants

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	RESP301+SoC n=11 Participants 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).	Standard of Care (SoC) n=5 Participants Participants received institutional SOC alone for the treatment of COVID-19.
Change in Room Air Oxygen Saturation (SpO2) From Baseline Over Time Day 1 - Change from baseline	0.1 Percent change Standard Deviation 2.84	NA Percent change Standard Deviation NA Post-dose nebulization did not occur in the SOC arm at Day 1. Soc arm data is not applicable.
Change in Room Air Oxygen Saturation (SpO2) From Baseline Over Time Day 2 - Change from baseline	-1.7 Percent change Standard Deviation 4.09	1.5 Percent change Standard Deviation 2.12
Change in Room Air Oxygen Saturation (SpO2) From Baseline Over Time Day 3 - Change from baseline	0.9 Percent change Standard Deviation 2.80	3.3 Percent change Standard Deviation 2.08
Change in Room Air Oxygen Saturation (SpO2) From Baseline Over Time Day 4 - Change from baseline	1.4 Percent change Standard Deviation 2.61	3.0 Percent change Standard Deviation 2.00
Change in Room Air Oxygen Saturation (SpO2) From Baseline Over Time Day 5 - Change from baseline	0.3 Percent change Standard Deviation 1.26	4.0 Percent change Standard Deviation 1.0
Change in Room Air Oxygen Saturation (SpO2) From Baseline Over Time Day 6 - Change from baseline	-1.0 Percent change Standard Deviation 1.41	4.5 Percent change Standard Deviation 3.54
Change in Room Air Oxygen Saturation (SpO2) From Baseline Over Time Day 7 - Change from baseline	3.0 Percent change Standard Deviation 2.83	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	RESP301+SoC n=12 Participants 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).	Standard of Care (SoC) n=5 Participants Participants received institutional SOC alone for the treatment of COVID-19.
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	-0.2 Score on a NEWS scale Standard Deviation 1.3
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	-0.5 Score on a NEWS scale Standard Deviation 3.11
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	1.4 Score on a NEWS scale Standard Deviation 0.89
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	0.5 Score on a NEWS scale Standard Deviation 0.58
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	-2.0 Score on a NEWS scale Standard Deviation 0.00
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	—

SECONDARY outcome

Timeframe: Day 1 (Baseline), Day 2, 3, 4, 5, 6, and 7

Population: The intent-to-treat (ITT) population included all randomized participants.

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.

Outcome measures

Outcome measures
Measure	RESP301+SoC n=12 Participants 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).	Standard of Care (SoC) n=5 Participants Participants received institutional SOC alone for the treatment of COVID-19.
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	0 Participants
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	5 Participants
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	0 Participants
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	0 Participants
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	0 Participants
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	0 Participants
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	0 Participants
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	0 Participants
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	0 Participants
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	0 Participants
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	0 Participants
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	0 Participants
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	0 Participants
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	0 Participants
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	0 Participants
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	0 Participants
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	0 Participants
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	0 Participants
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	0 Participants
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	1 Participants
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	4 Participants
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	0 Participants
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	0 Participants
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	0 Participants
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	0 Participants
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	4 Participants
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	0 Participants
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	0 Participants
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	0 Participants
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	0 Participants
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	0 Participants
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	1 Participants
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	2 Participants
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	1 Participants
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	0 Participants
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	0 Participants
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	0 Participants
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	2 Participants
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	0 Participants
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	0 Participants
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	0 Participants
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	0 Participants
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	0 Participants
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	0 Participants
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	0 Participants
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	0 Participants
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	0 Participants
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	0 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	RESP301+SoC n=12 Participants 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).	Standard of Care (SoC) n=5 Participants Participants received institutional SOC alone for the treatment of COVID-19.
Time to Improvement of at Least One Level Lower on the Modified WHO Ordinal Scale	4.00 Days Interval 2.0 to 10.5	5.00 Days Interval 5.0 to 3.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	RESP301+SoC n=1 Participants 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).	Standard of Care (SoC) Participants received institutional SOC alone for the treatment of COVID-19.
Time to Progression of at Least One Level Higher on the Modified WHO Ordinal Scale	NA Days As only 1 participant was evaluable, hence Median and Full range is not calculable.	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	RESP301+SoC n=14 Participants 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).	Standard of Care (SoC) n=5 Participants Participants received institutional SOC alone for the treatment of COVID-19.
Number of Participants With Adverse Events Participants with at least one AE	10 Participants	2 Participants
Number of Participants With Adverse Events Participants with at least one AE of Grade 3 or higher	1 Participants	0 Participants
Number of Participants With Adverse Events Participants with at least one treatment-related AE	3 Participants	0 Participants
Number of Participants With Adverse Events Participants with at least one severe AE	1 Participants	0 Participants
Number of Participants With Adverse Events Participants with at least one AE leading to study treatment withdrawal	3 Participants	0 Participants
Number of Participants With Adverse Events Participants with at least one treatment-related AE leading to study treatment withdrawal	1 Participants	0 Participants
Number of Participants With Adverse Events Participants with at least one AE leading to dose interruption	1 Participants	0 Participants
Number of Participants With Adverse Events Participants with at least one treatment-related AE leading to dose interruption	1 Participants	0 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	RESP301+SoC n=13 Participants 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).	Standard of Care (SoC) n=5 Participants Participants received institutional SOC alone for the treatment of COVID-19.
Time to Hospital Discharge	4.00 Days Interval 3.0 to 6.0	6.00 Days Interval 5.0 to 6.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	RESP301+SoC n=14 Participants 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).	Standard of Care (SoC) n=5 Participants Participants received institutional SOC alone for the treatment of COVID-19.
Number of Participants With Mortality by Day 28	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	RESP301+SoC n=2 Participants 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).	Standard of Care (SoC) Participants received institutional SOC alone for the treatment of COVID-19.
Reduction in Oxygen Saturation (SpO2) to <90% Day 1 Pre-Nebulization	95.0 Percent change Standard Deviation NA As only 1 participant was evaluable, hence SD is not calculable.	—
Reduction in Oxygen Saturation (SpO2) to <90% Day 1 Post-Nebulization	93.5 Percent change Standard Deviation 2.12	—
Reduction in Oxygen Saturation (SpO2) to <90% Day 2 Pre-Nebulization	94.0 Percent change Standard Deviation NA As only 1 participant was evaluable, hence SD is not calculable.	—
Reduction in Oxygen Saturation (SpO2) to <90% Day 2 Post-Nebulization	86.0 Percent change Standard Deviation NA As only 1 participant was evaluable, hence SD is not calculable.	—
Reduction in Oxygen Saturation (SpO2) to <90% Day 3 Pre-Nebulization	96.0 Percent change Standard Deviation NA As only 1 participant was evaluable, hence SD is not calculable.	—
Reduction in Oxygen Saturation (SpO2) to <90% Day 3 Post-Nebulization	94.0 Percent change Standard Deviation NA As only 1 participant was evaluable, hence SD is not calculable.	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	RESP301+SoC n=14 Participants 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).	Standard of Care (SoC) n=5 Participants Participants received institutional SOC alone for the treatment of COVID-19.
Events of Clinical Bronchial Hyper Responsiveness Related to Nebulization	2 Events	0 Events

Adverse Events

RESP301+SoC

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Standard of Care (SoC) Standard of Care (SoC)

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Alison Bracchi, MSc

Thirty Respiratory Ltd

Phone: +447763882519

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	RESP301+SoC n=14 participants at risk 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).	Standard of Care (SoC) Standard of Care (SoC) n=5 participants at risk Participants received institutional SOC alone for the treatment of COVID-19.
Respiratory, thoracic and mediastinal disorders Cough	7.1% 1/14 • Number of events 1 • From screening to safety follow up (30 days) 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.	20.0% 1/5 • Number of events 1 • From screening to safety follow up (30 days) 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.
Respiratory, thoracic and mediastinal disorders Oropharyngeal Discomfort	14.3% 2/14 • Number of events 2 • From screening to safety follow up (30 days) 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.	0.00% 0/5 • From screening to safety follow up (30 days) 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.
Respiratory, thoracic and mediastinal disorders Dyspnoea	7.1% 1/14 • Number of events 1 • From screening to safety follow up (30 days) 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.	0.00% 0/5 • From screening to safety follow up (30 days) 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.
Respiratory, thoracic and mediastinal disorders Epistaxis	7.1% 1/14 • Number of events 1 • From screening to safety follow up (30 days) 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.	0.00% 0/5 • From screening to safety follow up (30 days) 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.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/14 • From screening to safety follow up (30 days) 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.	20.0% 1/5 • Number of events 1 • From screening to safety follow up (30 days) 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.
Respiratory, thoracic and mediastinal disorders Oropharyngeal Pain	7.1% 1/14 • Number of events 1 • From screening to safety follow up (30 days) 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.	0.00% 0/5 • From screening to safety follow up (30 days) 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.
Respiratory, thoracic and mediastinal disorders Wheezing	7.1% 1/14 • Number of events 1 • From screening to safety follow up (30 days) 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.	0.00% 0/5 • From screening to safety follow up (30 days) 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.
Gastrointestinal disorders Constipation	7.1% 1/14 • Number of events 1 • From screening to safety follow up (30 days) 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.	20.0% 1/5 • Number of events 1 • From screening to safety follow up (30 days) 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.
Gastrointestinal disorders Abdominal Pain	7.1% 1/14 • Number of events 1 • From screening to safety follow up (30 days) 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.	0.00% 0/5 • From screening to safety follow up (30 days) 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.
Gastrointestinal disorders Diarrhoea	0.00% 0/14 • From screening to safety follow up (30 days) 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.	20.0% 1/5 • Number of events 1 • From screening to safety follow up (30 days) 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.
Gastrointestinal disorders Vomiting	7.1% 1/14 • Number of events 1 • From screening to safety follow up (30 days) 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.	0.00% 0/5 • From screening to safety follow up (30 days) 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.
Nervous system disorders Headache	7.1% 1/14 • Number of events 1 • From screening to safety follow up (30 days) 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.	20.0% 1/5 • Number of events 1 • From screening to safety follow up (30 days) 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.
Nervous system disorders Loss Of Consciousness	7.1% 1/14 • Number of events 1 • From screening to safety follow up (30 days) 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.	0.00% 0/5 • From screening to safety follow up (30 days) 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.
Nervous system disorders Paraesthesia	7.1% 1/14 • Number of events 1 • From screening to safety follow up (30 days) 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.	0.00% 0/5 • From screening to safety follow up (30 days) 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.
General disorders Chest Pain	7.1% 1/14 • Number of events 1 • From screening to safety follow up (30 days) 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.	0.00% 0/5 • From screening to safety follow up (30 days) 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.
General disorders Non-Cardiac Chest Pain	0.00% 0/14 • From screening to safety follow up (30 days) 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.	20.0% 1/5 • Number of events 1 • From screening to safety follow up (30 days) 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.
General disorders Oedema	7.1% 1/14 • Number of events 1 • From screening to safety follow up (30 days) 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.	0.00% 0/5 • From screening to safety follow up (30 days) 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.
General disorders Peripheral Swelling	0.00% 0/14 • From screening to safety follow up (30 days) 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.	20.0% 1/5 • Number of events 1 • From screening to safety follow up (30 days) 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.
Investigations Oxygen Saturation Decreased	14.3% 2/14 • Number of events 3 • From screening to safety follow up (30 days) 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.	0.00% 0/5 • From screening to safety follow up (30 days) 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.
Investigations Liver Function Test Increased	7.1% 1/14 • Number of events 1 • From screening to safety follow up (30 days) 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.	0.00% 0/5 • From screening to safety follow up (30 days) 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.
Investigations Lymphocyte Count Decreased	7.1% 1/14 • Number of events 1 • From screening to safety follow up (30 days) 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.	0.00% 0/5 • From screening to safety follow up (30 days) 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.
Infections and infestations Respiratory Tract Infection	7.1% 1/14 • Number of events 1 • From screening to safety follow up (30 days) 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.	0.00% 0/5 • From screening to safety follow up (30 days) 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.
Infections and infestations Sepsis	7.1% 1/14 • Number of events 1 • From screening to safety follow up (30 days) 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.	0.00% 0/5 • From screening to safety follow up (30 days) 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.
Musculoskeletal and connective tissue disorders Back Pain	0.00% 0/14 • From screening to safety follow up (30 days) 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.	20.0% 1/5 • Number of events 1 • From screening to safety follow up (30 days) 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.
Musculoskeletal and connective tissue disorders Pain In Extremity	7.1% 1/14 • Number of events 1 • From screening to safety follow up (30 days) 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.	0.00% 0/5 • From screening to safety follow up (30 days) 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.