Trial Outcomes & Findings for Study to Assess Efficacy and Safety of Inhaled Interferon-β Therapy for COVID-19 (NCT NCT04732949)

Last Updated: 2023-03-27

Results Overview

The time to hospital discharge in patients with moderate COVID-19 after administration of SNG001 compared to placebo was evaluated.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

623 participants

Primary outcome timeframe

Day 28

Results posted on

2023-03-27

Participant Flow

This trial was conducted at 112 centers which included 623 patients across 17 countries. The trial began on 12 January 2021 (first patient consented) and was completed on 10 Feb 2022.

The pre-treatment assessments were performed on Day 0 prior to the first dose preferably. All the study assessments were performed as per the schedule of assessments.

Participant milestones

Participant milestones
Measure	SNG001 Patients received SNG001 via inhalation using nebuliser, once a day for 14 days	Placebo Patients received Placebo via inhalation using nebuliser, once a day for 14 days
Overall Study STARTED	309	314
Overall Study COMPLETED	233	231
Overall Study NOT COMPLETED	76	83

Reasons for withdrawal

Reasons for withdrawal
Measure	SNG001 Patients received SNG001 via inhalation using nebuliser, once a day for 14 days	Placebo Patients received Placebo via inhalation using nebuliser, once a day for 14 days
Overall Study Withdrawal by Subject	23	27
Overall Study Protocol Violation	0	1
Overall Study Non-compliance	0	2
Overall Study Physician Decision	2	1
Overall Study Serious adverse event (Fatal)	16	18
Overall Study Serious adverse event (Non fatal)	2	1
Overall Study Non-serious adverse event	1	3
Overall Study Lost to Follow-up	26	27
Overall Study Other	6	3

Baseline Characteristics

Study to Assess Efficacy and Safety of Inhaled Interferon-β Therapy for COVID-19

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	SNG001 n=309 Participants Patients received SNG001 via inhalation using nebuliser, once a day for 14 days	Placebo n=314 Participants Patients received Placebo via inhalation using nebuliser, once a day for 14 days	Total n=623 Participants Total of all reporting groups
Age, Continuous	52 years STANDARD_DEVIATION 15.19 • n=5 Participants	53.7 years STANDARD_DEVIATION 14.42 • n=7 Participants	52.8 years STANDARD_DEVIATION 14.82 • n=5 Participants
Sex: Female, Male Female	203 Participants n=5 Participants	208 Participants n=7 Participants	411 Participants n=5 Participants
Sex: Female, Male Male	106 Participants n=5 Participants	106 Participants n=7 Participants	212 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	53 Participants n=5 Participants	49 Participants n=7 Participants	102 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	238 Participants n=5 Participants	242 Participants n=7 Participants	480 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	18 Participants n=5 Participants	23 Participants n=7 Participants	41 Participants n=5 Participants
Race/Ethnicity, Customized White	224 Participants n=5 Participants	215 Participants n=7 Participants	439 Participants n=5 Participants
Race/Ethnicity, Customized Black	7 Participants n=5 Participants	6 Participants n=7 Participants	13 Participants n=5 Participants
Race/Ethnicity, Customized Asian- Chinese	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Asian- Other	40 Participants n=5 Participants	46 Participants n=7 Participants	86 Participants n=5 Participants
Race/Ethnicity, Customized Arab	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants
Race/Ethnicity, Customized American Indian	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Race/Ethnicity, Customized Other	10 Participants n=5 Participants	13 Participants n=7 Participants	23 Participants n=5 Participants
Race/Ethnicity, Customized Unknown	19 Participants n=5 Participants	22 Participants n=7 Participants	41 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 28

Population: The Intent-to-Treat (ITT) analysis population consisted of all randomised patients.

The time to hospital discharge in patients with moderate COVID-19 after administration of SNG001 compared to placebo was evaluated.

Outcome measures

Outcome measures
Measure	SNG001 n=309 Participants Patients received SNG001 via inhalation using nebuliser, once a day for 14 days	Placebo n=314 Participants Patients received Placebo via inhalation using nebuliser, once a day for 14 days
Time to Hospital Discharge	7.0 days Interval 7.0 to 8.0	8.0 days Interval 7.0 to 9.0

PRIMARY outcome

Timeframe: Day 28

Population: The ITT analysis population consisted of all randomised patients.

Recovery in patients with moderate COVID-19 after administration of SNG001 compared to placebo by time to recovery was evaluated.

Outcome measures

Outcome measures
Measure	SNG001 n=309 Participants Patients received SNG001 via inhalation using nebuliser, once a day for 14 days	Placebo n=314 Participants Patients received Placebo via inhalation using nebuliser, once a day for 14 days
Time to Recovery	25.0 days Interval 22.0 to Not calculable due to Insufficient number of participants with events	25.0 days Interval 22.0 to Not calculable due to Insufficient number of participants with events

SECONDARY outcome

Timeframe: Until Day 35

Population: The ITT analysis population consisted of all randomised patients. Here, the number of participants analyzed signifies the participants with available data that were analyzed for this outcome measure.

The efficacy of SNG001 compared to placebo in patients with moderate COVID-19 by assessing progression to severe disease or death was evaluated. Severe disease was defined by the Ordinal Scale for Clinical Improvement (OSCI) as a score between 5 and 7. Death was defined by an OSCI score of 8.

Outcome measures

Outcome measures
Measure	SNG001 n=308 Participants Patients received SNG001 via inhalation using nebuliser, once a day for 14 days	Placebo n=312 Participants Patients received Placebo via inhalation using nebuliser, once a day for 14 days
Number of Patients Who Progressed to Severe Disease or Death	33 Participants	45 Participants

SECONDARY outcome

Timeframe: Until Day 35

Population: The ITT analysis population consisted of all randomised patients.

The efficacy of SNG001 compared to placebo in patients with moderate COVID-19 by assessing progression to intubation or death was evaluated. Intubation was defined by the OSCI as a score between 6 and 7. Death was defined by an OSCI score of 8.

Outcome measures

Outcome measures
Measure	SNG001 n=309 Participants Patients received SNG001 via inhalation using nebuliser, once a day for 14 days	Placebo n=314 Participants Patients received Placebo via inhalation using nebuliser, once a day for 14 days
Number of Patients Who Were Intubated or Who Died	20 Participants	23 Participants

SECONDARY outcome

Timeframe: Until Day 35 of first dose

Population: The ITT analysis population consisted of all randomised patients.

Patients who died within 35 days of first dose of study intervention were calculated.

Outcome measures

Outcome measures
Measure	SNG001 n=309 Participants Patients received SNG001 via inhalation using nebuliser, once a day for 14 days	Placebo n=314 Participants Patients received Placebo via inhalation using nebuliser, once a day for 14 days
Number of Patients Who Died Within 35 Days of First Dose	14 Participants	17 Participants

SECONDARY outcome

Timeframe: Days 7, 14, 21 and 28

Population: The ITT analysis population consisted of all randomised patients.

The efficacy of SNG001 compared to placebo in patients with moderate COVID-19 was assessed by hospital discharge on given days.

Outcome measures

Outcome measures
Measure	SNG001 n=309 Participants Patients received SNG001 via inhalation using nebuliser, once a day for 14 days	Placebo n=314 Participants Patients received Placebo via inhalation using nebuliser, once a day for 14 days
Cumulative Number of Patients Who Were Discharged From Hospital Day 7	154 Participants	141 Participants
Cumulative Number of Patients Who Were Discharged From Hospital Day 14	231 Participants	223 Participants
Cumulative Number of Patients Who Were Discharged From Hospital Day 21	245 Participants	249 Participants
Cumulative Number of Patients Who Were Discharged From Hospital Day 28	249 Participants	255 Participants

SECONDARY outcome

Timeframe: Days 7, 14, 21 and 28

Population: The ITT analysis population consisted of all randomised patients.

The efficacy of SNG001 compared to placebo in patients with moderate COVID-19 by assessing recovery was evaluated. Recovery is defined as no limitation of activities according to the Ordinal Scale of Clinical Improvement (OSCI), with no rebound at subsequent assessments.

Outcome measures

Outcome measures
Measure	SNG001 n=309 Participants Patients received SNG001 via inhalation using nebuliser, once a day for 14 days	Placebo n=314 Participants Patients received Placebo via inhalation using nebuliser, once a day for 14 days
Cumulative Number of Patients With Recovery Day 7	28 Participants	17 Participants
Cumulative Number of Patients With Recovery Day 14	75 Participants	73 Participants
Cumulative Number of Patients With Recovery Day 21	117 Participants	118 Participants
Cumulative Number of Patients With Recovery Day 28	145 Participants	151 Participants

SECONDARY outcome

Timeframe: Until Day 35

The efficacy of SNG001 compared to placebo in patients with moderate COVID-19 by assessing improvement across the entire WHO OSCI were evaluated. Improvement in clinical status is based on the 9-point OSCI score. The score ranges from 0 to 8, where lower score of 0 represents no clinical or virological evidence of infection and higher score of 8 represents death.Higher scores indicated worse outcome.

Outcome measures

Outcome measures
Measure	SNG001 n=309 Participants Patients received SNG001 via inhalation using nebuliser, once a day for 14 days	Placebo n=314 Participants Patients received Placebo via inhalation using nebuliser, once a day for 14 days
Improvement Based on Entire WHO OSCI Score Day 35 · 8 = Death	14 Participants	17 Participants
Improvement Based on Entire WHO OSCI Score Baseline · 0 = No clinical or virological evidence of infection	0 Participants	0 Participants
Improvement Based on Entire WHO OSCI Score Baseline · 1 = No limitations of activities	0 Participants	0 Participants
Improvement Based on Entire WHO OSCI Score Baseline · 2 = Limitation of activities	1 Participants	0 Participants
Improvement Based on Entire WHO OSCI Score Baseline · 3 = Hospitalised - no oxygen therapy	3 Participants	8 Participants
Improvement Based on Entire WHO OSCI Score Baseline · 4 = Oxygen by mask, or nasal prongs	304 Participants	304 Participants
Improvement Based on Entire WHO OSCI Score Baseline · 5 = Non-invasive ventilation, or high flow oxygen	1 Participants	2 Participants
Improvement Based on Entire WHO OSCI Score Baseline · 6 = Intubation and mechanical ventilation	0 Participants	0 Participants
Improvement Based on Entire WHO OSCI Score Baseline · 7 = Ventilation plus additional organ support	0 Participants	0 Participants
Improvement Based on Entire WHO OSCI Score Baseline · 8 = Death	0 Participants	0 Participants
Improvement Based on Entire WHO OSCI Score Baseline · Missing	0 Participants	0 Participants
Improvement Based on Entire WHO OSCI Score Day 7 · 0 = No clinical or virological evidence of infection	20 Participants	14 Participants
Improvement Based on Entire WHO OSCI Score Day 7 · 1 = No limitations of activities	18 Participants	12 Participants
Improvement Based on Entire WHO OSCI Score Day 7 · 2 = Limitation of activities	115 Participants	114 Participants
Improvement Based on Entire WHO OSCI Score Day 7 · 3 = Hospitalised - no oxygen therapy	42 Participants	42 Participants
Improvement Based on Entire WHO OSCI Score Day 7 · 4 = Oxygen by mask, or nasal prongs	53 Participants	69 Participants
Improvement Based on Entire WHO OSCI Score Day 7 · 5 = Non-invasive ventilation, or high flow oxygen	18 Participants	26 Participants
Improvement Based on Entire WHO OSCI Score Day 7 · 6 = Intubation and mechanical ventilation	2 Participants	2 Participants
Improvement Based on Entire WHO OSCI Score Day 7 · 7 = Ventilation plus additional organ support	3 Participants	3 Participants
Improvement Based on Entire WHO OSCI Score Day 7 · 8 = Death	4 Participants	0 Participants
Improvement Based on Entire WHO OSCI Score Day 7 · Missing	34 Participants	32 Participants
Improvement Based on Entire WHO OSCI Score Day 14 · 0 = No clinical or virological evidence of infection	62 Participants	57 Participants
Improvement Based on Entire WHO OSCI Score Day 14 · 1 = No limitations of activities	24 Participants	30 Participants
Improvement Based on Entire WHO OSCI Score Day 14 · 2 = Limitation of activities	135 Participants	127 Participants
Improvement Based on Entire WHO OSCI Score Day 14 · 3 = Hospitalised - no oxygen therapy	11 Participants	18 Participants
Improvement Based on Entire WHO OSCI Score Day 14 · 4 = Oxygen by mask, or nasal prongs	13 Participants	15 Participants
Improvement Based on Entire WHO OSCI Score Day 14 · 5 = Non-invasive ventilation, or high flow oxygen	2 Participants	4 Participants
Improvement Based on Entire WHO OSCI Score Day 14 · 6 = Intubation and mechanical ventilation	3 Participants	1 Participants
Improvement Based on Entire WHO OSCI Score Day 14 · 7 = Ventilation plus additional organ support	3 Participants	9 Participants
Improvement Based on Entire WHO OSCI Score Day 14 · 8 = Death	9 Participants	7 Participants
Improvement Based on Entire WHO OSCI Score Day 14 · Missing	47 Participants	46 Participants
Improvement Based on Entire WHO OSCI Score Day 21 · 0 = No clinical or virological evidence of infection	89 Participants	94 Participants
Improvement Based on Entire WHO OSCI Score Day 21 · 1 = No limitations of activities	32 Participants	23 Participants
Improvement Based on Entire WHO OSCI Score Day 21 · 2 = Limitation of activities	109 Participants	114 Participants
Improvement Based on Entire WHO OSCI Score Day 21 · 3 = Hospitalised - no oxygen therapy	3 Participants	4 Participants
Improvement Based on Entire WHO OSCI Score Day 21 · 4 = Oxygen by mask, or nasal prongs	7 Participants	4 Participants
Improvement Based on Entire WHO OSCI Score Day 21 · 5 = Non-invasive ventilation, or high flow oxygen	1 Participants	0 Participants
Improvement Based on Entire WHO OSCI Score Day 21 · 6 = Intubation and mechanical ventilation	2 Participants	1 Participants
Improvement Based on Entire WHO OSCI Score Day 21 · 7 = Ventilation plus additional organ support	2 Participants	8 Participants
Improvement Based on Entire WHO OSCI Score Day 21 · 8 = Death	12 Participants	9 Participants
Improvement Based on Entire WHO OSCI Score Day 21 · Missing	52 Participants	57 Participants
Improvement Based on Entire WHO OSCI Score Day 28 · 0 = No clinical or virological evidence of infection	123 Participants	134 Participants
Improvement Based on Entire WHO OSCI Score Day 28 · 1 = No limitations of activities	23 Participants	13 Participants
Improvement Based on Entire WHO OSCI Score Day 28 · 2 = Limitation of activities	85 Participants	95 Participants
Improvement Based on Entire WHO OSCI Score Day 28 · 3 = Hospitalised - no oxygen therapy	0 Participants	0 Participants
Improvement Based on Entire WHO OSCI Score Day 28 · 4 = Oxygen by mask, or nasal prongs	3 Participants	2 Participants
Improvement Based on Entire WHO OSCI Score Day 28 · 5 = Non-invasive ventilation, or high flow oxygen	4 Participants	0 Participants
Improvement Based on Entire WHO OSCI Score Day 28 · 6 = Intubation and mechanical ventilation	0 Participants	1 Participants
Improvement Based on Entire WHO OSCI Score Day 28 · 7 = Ventilation plus additional organ support	1 Participants	3 Participants
Improvement Based on Entire WHO OSCI Score Day 28 · 8 = Death	14 Participants	14 Participants
Improvement Based on Entire WHO OSCI Score Day 28 · Missing	56 Participants	52 Participants
Improvement Based on Entire WHO OSCI Score Day 35 · 0 = No clinical or virological evidence of infection	147 Participants	153 Participants
Improvement Based on Entire WHO OSCI Score Day 35 · 1 = No limitations of activities	10 Participants	16 Participants
Improvement Based on Entire WHO OSCI Score Day 35 · 2 = Limitation of activities	71 Participants	73 Participants
Improvement Based on Entire WHO OSCI Score Day 35 · 3 = Hospitalised - no oxygen therapy	0 Participants	0 Participants
Improvement Based on Entire WHO OSCI Score Day 35 · 4 = Oxygen by mask, or nasal prongs	2 Participants	1 Participants
Improvement Based on Entire WHO OSCI Score Day 35 · 5 = Non-invasive ventilation, or high flow oxygen	1 Participants	0 Participants
Improvement Based on Entire WHO OSCI Score Day 35 · 6 = Intubation and mechanical ventilation	2 Participants	1 Participants
Improvement Based on Entire WHO OSCI Score Day 35 · 7 = Ventilation plus additional organ support	1 Participants	1 Participants
Improvement Based on Entire WHO OSCI Score Day 35 · Missing	61 Participants	52 Participants

SECONDARY outcome

Timeframe: Baseline to Day 15

Population: The ITT analysis population consisted of all randomised patients.

The efficacy of SNG001 compared with placebo in patients with moderate COVID-19 by assessing changes in daily breathlessness, cough and sputum scores on a scale of 0 (no symptoms) up to 4 (severe symptoms) was evaluated. Breathlessness, Cough and Sputum is graded on a score from 0 to 4, where a higher score indicates worse symptoms. The total score is calculated by summing the individual scores and is therefore graded on a scale from 0 to 12. Change in value of BCSS total scale, with negative value indicates an improvement in symptoms.

Outcome measures

Outcome measures
Measure	SNG001 n=309 Participants Patients received SNG001 via inhalation using nebuliser, once a day for 14 days	Placebo n=314 Participants Patients received Placebo via inhalation using nebuliser, once a day for 14 days
Change From Baseline in Total Score According to the Breathlessness, Cough and Sputum Scale (BCSS)	-2.1 score on a scale Standard Error 0.09	-2.2 score on a scale Standard Error 0.09

SECONDARY outcome

Timeframe: Day 1 until Day 28

The efficacy of SNG001 compared to placebo in patients with moderate COVID-19 by assessing changes in NEWS2 during hospitalisation period was evaluated. It is the sum of scores calculated for Respiratory rate, Oxygen Saturation, Systolic BP, Pulse and Temperature when graded on a scale from 0 to 3 where 0 means a normal assessment and a higher score indicates a greater deviation from normal . 2 more points are added if the patient is receiving oxygen and 3 further points are added if the patient has new-onset confusion, disorientation and/or agitation, where previously their mental state was normal. This gives a score between 0 and 20. Higher scores indicates high clinical risk. Change from baseline in NEWS-2 score, in negative values favors improvement.

Outcome measures

Outcome measures
Measure	SNG001 n=75 Participants Patients received SNG001 via inhalation using nebuliser, once a day for 14 days	Placebo n=87 Participants Patients received Placebo via inhalation using nebuliser, once a day for 14 days
Change From Baseline in National Early Warning Score (NEWS2) During the Hospitalisation Period Day 7	-0.7 score on a scale Standard Deviation 3.08	-0.7 score on a scale Standard Deviation 2.55
Change From Baseline in National Early Warning Score (NEWS2) During the Hospitalisation Period Day 14	0.2 score on a scale Standard Deviation 3.83	-0.3 score on a scale Standard Deviation 3.32
Change From Baseline in National Early Warning Score (NEWS2) During the Hospitalisation Period Day 21	2.8 score on a scale Standard Deviation 3.16	2.3 score on a scale Standard Deviation 3.62
Change From Baseline in National Early Warning Score (NEWS2) During the Hospitalisation Period Day 28	-0.5 score on a scale Standard Deviation 2.08	4.5 score on a scale Standard Deviation 4.37

SECONDARY outcome

Timeframe: Day 1 until Day 90

Population: The ITT analysis population consisted of all randomised patients.

The efficacy of SNG001 compared to placebo in patients with moderate COVID-19 by daily assessment of COVID-19 symptoms was evaluated. The presence of COVID-19 symptoms were assessed. Individual symptoms related to COVID-19/SARS-CoV-2 infection such as fever, breathlessness, and fatigue were assessed.

Outcome measures

Outcome measures
Measure	SNG001 n=309 Participants Patients received SNG001 via inhalation using nebuliser, once a day for 14 days	Placebo n=314 Participants Patients received Placebo via inhalation using nebuliser, once a day for 14 days
Number of Patients With Presence of COVID-19 Symptoms Based on Daily Assessment Baseline	306 Participants	310 Participants
Number of Patients With Presence of COVID-19 Symptoms Based on Daily Assessment Day 7	221 Participants	234 Participants
Number of Patients With Presence of COVID-19 Symptoms Based on Daily Assessment Day 14	169 Participants	162 Participants
Number of Patients With Presence of COVID-19 Symptoms Based on Daily Assessment Day 21	154 Participants	139 Participants
Number of Patients With Presence of COVID-19 Symptoms Based on Daily Assessment Day 28	122 Participants	117 Participants
Number of Patients With Presence of COVID-19 Symptoms Based on Daily Assessment Day 35	61 Participants	69 Participants
Number of Patients With Presence of COVID-19 Symptoms Based on Daily Assessment Day 60	44 Participants	57 Participants
Number of Patients With Presence of COVID-19 Symptoms Based on Daily Assessment Day 90	41 Participants	51 Participants

SECONDARY outcome

Timeframe: Day 1 until Day 35

Population: The ITT analysis population consisted of all randomised patients.

The efficacy of SNG001 compared to placebo in patients with moderate COVID-19 by daily assessment of limitation of usual activities was evaluated. The patients with limitations of usual activities were the patients who were unable to do usual activities (work, study, housework, family or leisure activities).

Outcome measures

Outcome measures
Measure	SNG001 n=309 Participants Patients received SNG001 via inhalation using nebuliser, once a day for 14 days	Placebo n=314 Participants Patients received Placebo via inhalation using nebuliser, once a day for 14 days
Number of Patients With Limitations of Usual Activities Based on Daily Assessment Day 35	71 Participants	73 Participants
Number of Patients With Limitations of Usual Activities Based on Daily Assessment Day 1	0 Participants	1 Participants
Number of Patients With Limitations of Usual Activities Based on Daily Assessment Day 7	115 Participants	114 Participants
Number of Patients With Limitations of Usual Activities Based on Daily Assessment Day 14	135 Participants	127 Participants
Number of Patients With Limitations of Usual Activities Based on Daily Assessment Day 21	109 Participants	114 Participants
Number of Patients With Limitations of Usual Activities Based on Daily Assessment Day 28	85 Participants	95 Participants

SECONDARY outcome

Timeframe: Day 0, Day 7, Day 15, Day 28, Day 60 and Day 90

The efficacy of SNG001 compared to placebo in patients with moderate COVID-19 by using EQ-5D-5L was evaluated. The EQ-5D-5L provides a simple descriptive profile and a single index value for health status. The EQ-5D-5L self-rated questionnaire includes a visual analogue scale, which records the respondent's self-rated health status on a graduated (0-100) scale, with higher scores for higher health-related quality of life. It also includes the EQ-5D-5L descriptive system, which comprises 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The responses record five levels of severity (no problems/slight problems/moderate problems/severe problems/extreme problems) within a particular EQ-5D dimension. Here, 100 means the best health and 0 means the worst health.

Outcome measures

Outcome measures
Measure	SNG001 n=302 Participants Patients received SNG001 via inhalation using nebuliser, once a day for 14 days	Placebo n=311 Participants Patients received Placebo via inhalation using nebuliser, once a day for 14 days
Quality of Life Measured Using EuroQol 5-dimension 5-level (EQ-5D-5L) Day 0	56.4 score on a scale Standard Deviation 21.72	56.9 score on a scale Standard Deviation 20.95
Quality of Life Measured Using EuroQol 5-dimension 5-level (EQ-5D-5L) Day 7	72.6 score on a scale Standard Deviation 18.39	71.1 score on a scale Standard Deviation 20.44
Quality of Life Measured Using EuroQol 5-dimension 5-level (EQ-5D-5L) Day 15	79.5 score on a scale Standard Deviation 18.25	79.0 score on a scale Standard Deviation 16.51
Quality of Life Measured Using EuroQol 5-dimension 5-level (EQ-5D-5L) Day 28	83.3 score on a scale Standard Deviation 16.00	83.5 score on a scale Standard Deviation 14.90
Quality of Life Measured Using EuroQol 5-dimension 5-level (EQ-5D-5L) Day 60	88.9 score on a scale Standard Deviation 14.16	88.0 score on a scale Standard Deviation 13.56
Quality of Life Measured Using EuroQol 5-dimension 5-level (EQ-5D-5L) Day 90	90.3 score on a scale Standard Deviation 12.65	89.9 score on a scale Standard Deviation 13.65

SECONDARY outcome

Timeframe: Day 15, Day 28, Day 60 and Day 90

The efficacy of SNG001 compared to placebo in patients with moderate COVID-19 by assessing long-COVID-19 symptoms was evaluated. Assessment of long-COVID-19 symptoms based on GAD-7 scale. GAD-7 scores seven individual item scales by assigning scores of 0, 1, 2, and 3, to the response categories of "not at all", "several days", "more than half the days", and "nearly every day", respectively. The GAD-7 total score is calculated by summing the individual item scales to give a total score between 0 and 21. Higher score indicates severe anxiety.

Outcome measures

Outcome measures
Measure	SNG001 n=238 Participants Patients received SNG001 via inhalation using nebuliser, once a day for 14 days	Placebo n=249 Participants Patients received Placebo via inhalation using nebuliser, once a day for 14 days
General Anxiety Disorder 7 Questionnaire (GAD-7) Total Score Day 28	2.2 score on a scale Standard Deviation 3.67	1.9 score on a scale Standard Deviation 3.29
General Anxiety Disorder 7 Questionnaire (GAD-7) Total Score Day 15	3.3 score on a scale Standard Deviation 4.08	3.5 score on a scale Standard Deviation 4.30
General Anxiety Disorder 7 Questionnaire (GAD-7) Total Score Day 60	1.4 score on a scale Standard Deviation 3.06	1.7 score on a scale Standard Deviation 3.38
General Anxiety Disorder 7 Questionnaire (GAD-7) Total Score Day 90	1.0 score on a scale Standard Deviation 2.41	1.6 score on a scale Standard Deviation 3.43

SECONDARY outcome

Timeframe: Day 15, Day 28, Day 60 and Day 90

Long-COVID-19 symptoms based on FACIT Fatigue Scale (Version 4) were evaluated. The FACIT Fatigue Scale (Version 4) included statements for patients such as: I feel fatigued; I feel weak all over; I feel listless ("washed out"); I feel tired; I have trouble starting things because I am tired; I have trouble finishing things because I am tired; I have energy; I am able to do my usual activities; I need to sleep during the day; I am too tired to eat; I need help doing my usual activities; and I am frustrated by being too tired to do the things I want to do. Based on responses on above statements, scoring was done and scores ranges from 0 to 4, where 0 represents not at all bothered by any of the above problems and 4 indicates very much bothered every day by any of the above problems. Total scores will be calculated as per the algorithm to give a total score on a scale between 0 and 52, where a higher total score indicates lower level of fatigue.

Outcome measures

Outcome measures
Measure	SNG001 n=239 Participants Patients received SNG001 via inhalation using nebuliser, once a day for 14 days	Placebo n=248 Participants Patients received Placebo via inhalation using nebuliser, once a day for 14 days
Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-FS [Version 4]) Total Score Day 15	39.1 score on a scale Standard Deviation 9.79	38.7 score on a scale Standard Deviation 10.31
Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-FS [Version 4]) Total Score Day 28	42.5 score on a scale Standard Deviation 10.19	42.8 score on a scale Standard Deviation 8.98
Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-FS [Version 4]) Total Score Day 60	46.4 score on a scale Standard Deviation 8.22	45.5 score on a scale Standard Deviation 7.96
Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-FS [Version 4]) Total Score Day 90	46.9 score on a scale Standard Deviation 8.01	46.3 score on a scale Standard Deviation 7.78

SECONDARY outcome

Timeframe: Day 15, Day 28, Day 60 and Day 90

Long-COVID-19 symptoms based on PHQ-9 were evaluated. Patient Health Questionnaire-9 (PHQ-9) scores nine individual item scales by assigning scores of 0, 1, 2, and 3, to the response categories of "not at all", "several days", "more than half the days", and "nearly every day", respectively. PHQ-9 total scores are calculated by summing the individual item scales to give a total score between 0 and 27. Higher scores indicated worse outcome.

Outcome measures

Outcome measures
Measure	SNG001 n=237 Participants Patients received SNG001 via inhalation using nebuliser, once a day for 14 days	Placebo n=245 Participants Patients received Placebo via inhalation using nebuliser, once a day for 14 days
Patient Health Questionnaire-9 (PHQ-9) Total Score Day 15	4.6 score on a scale Standard Deviation 4.47	5.0 score on a scale Standard Deviation 4.71
Patient Health Questionnaire-9 (PHQ-9) Total Score Day 28	3.2 score on a scale Standard Deviation 4.15	3.1 score on a scale Standard Deviation 4.02
Patient Health Questionnaire-9 (PHQ-9) Total Score Day 60	1.7 score on a scale Standard Deviation 3.23	2.1 score on a scale Standard Deviation 3.85
Patient Health Questionnaire-9 (PHQ-9) Total Score Day 90	1.5 score on a scale Standard Deviation 3.05	2.0 score on a scale Standard Deviation 3.89

SECONDARY outcome

Timeframe: Day 15, Day 28, Day 60 and Day 90

Brief Pain Inventory Composite Scores is a self administered questionnaire that assesses pain interference. Overall pain severity score is calculated as the mean of questions of the brief pain inventory. The overall pain severity score is the average pain, on a scale from 0 to 10 of the worst pain, least pain and average pain in the last 24 hours and pain right now scores. Here, 0 indicates "No pain" and 10 indicates "Worst pain".

Outcome measures

Outcome measures
Measure	SNG001 n=50 Participants Patients received SNG001 via inhalation using nebuliser, once a day for 14 days	Placebo n=55 Participants Patients received Placebo via inhalation using nebuliser, once a day for 14 days
Overall Pain Severity as Measured by Brief Pain Inventory Composite Scores Day 15	3.4 score on a scale Standard Deviation 2.13	3.3 score on a scale Standard Deviation 1.98
Overall Pain Severity as Measured by Brief Pain Inventory Composite Scores Day 28	3.2 score on a scale Standard Deviation 1.98	3.2 score on a scale Standard Deviation 1.77
Overall Pain Severity as Measured by Brief Pain Inventory Composite Scores Day 60	4.1 score on a scale Standard Deviation 1.54	3.3 score on a scale Standard Deviation 1.94
Overall Pain Severity as Measured by Brief Pain Inventory Composite Scores Day 90	4.5 score on a scale Standard Deviation 2.14	3.5 score on a scale Standard Deviation 2.33

SECONDARY outcome

Timeframe: From the day informed consent is obtained until 28 days after the last administration of the study medication (Day 90)

Population: The Safety analysis population included all patients in the ITT population who receive at least one dose of study drug.

The general safety and tolerability of SNG001 compared to placebo when administered to patients with moderate COVID-19 by assessing number of patients with AEs was assessed.

Outcome measures

Outcome measures
Measure	SNG001 n=301 Participants Patients received SNG001 via inhalation using nebuliser, once a day for 14 days	Placebo n=303 Participants Patients received Placebo via inhalation using nebuliser, once a day for 14 days
Number of Patients With Adverse Events (AEs) and Serious Adverse Events (SAEs) Any Treatment-emergent adverse event (TEAE)	251 Participants	251 Participants
Number of Patients With Adverse Events (AEs) and Serious Adverse Events (SAEs) Any serious TEAE	38 Participants	55 Participants
Number of Patients With Adverse Events (AEs) and Serious Adverse Events (SAEs) Any serious related TEAE	3 Participants	3 Participants
Number of Patients With Adverse Events (AEs) and Serious Adverse Events (SAEs) Any fatal TEAE	16 Participants	16 Participants
Number of Patients With Adverse Events (AEs) and Serious Adverse Events (SAEs) Any fatal TEAE related to study treatment	0 Participants	0 Participants
Number of Patients With Adverse Events (AEs) and Serious Adverse Events (SAEs) Any TEAE related to study treatment	68 Participants	77 Participants
Number of Patients With Adverse Events (AEs) and Serious Adverse Events (SAEs) Any TEAE leading to discontinuation of study treatment	24 Participants	23 Participants
Number of Patients With Adverse Events (AEs) and Serious Adverse Events (SAEs) Any Adverse Events of Note	0 Participants	1 Participants

Adverse Events

SNG001

Serious events: 38 serious events

Other events: 250 other events

Deaths: 16 deaths

Placebo

Serious events: 55 serious events

Other events: 248 other events

Deaths: 18 deaths

Serious adverse events

Other adverse events

Additional Information

Brooke Clarke, SVP, Head of Communications

Synairgen

Phone: 02380 512 800

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee This document is the property of Synairgen Research Ltd and may not be used, divulged, published, or otherwise disclosed with.
Publication restrictions are in place

Restriction type: OTHER