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

Study Overview
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Brief Summary
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The purpose of this Phase III study is to confirm that SNG001 can accelerate the recovery of hospitalised patients receiving oxygen with confirmed Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2). Safety and other efficacy endpoints will also be assessed.

Detailed Description
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Eligible patients with SARS-CoV-2 infection confirmed by a positive virus test and who are hospitalised due to COVID-19 and require oxygen therapy, will be randomised in a 1:1 ratio to receive SNG001 two syringes or placebo two syringes. SNG001 or placebo will be administered via the Ultra nebuliser. Patients will receive a dose of SNG001 or placebo once a day for 14 days and will be followed up for up to 90 days after the first dose of study medication. Study data will be collected from patients daily, as per the study schedule.

Official Title
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A Randomised, Double-blind, Placebo-controlled, Phase III Trial to Determine the Efficacy and Safety of Inhaled SNG001 for the Treatment of Patients Hospitalised Due to Moderate COVID-19

Conditions
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Severe Acute Respiratory Syndrome Coronavirus 2, COVID-19

Intervention / Treatment
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* Drug: SNG001
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Admitted to hospital due to the severity of their COVID-19 Positive virus test for SARS-CoV-2 using a validated molecular assay or antigen assay. Patients who had a positive virus test for SARS-CoV-2 prior to hospitalisation will be randomised no later than 48 hours after hospital admission. If the virus test is performed more than 96 hours prior to hospitalisation, the test will have to be repeated in the hospital prior to randomisation. Only patients whose repeated virus test is positive will be randomised, no later than 48 hours after confirmation of SARS-CoV-2 infection. Patients who had their first positive virus test for SARS-CoV-2 after hospitalisation will be randomised no later than 48 hours after confirmation of SARS-CoV-2 infection Require oxygen therapy via nasal prongs or mask (WHO OSCI score of 4) Provided informed consent Female patients must be ≥1 year post-menopausal, surgically sterile, or using a protocol defined highly effective method of contraception Women of child bearing potential should have been stable on their chosen method of birth control for a minimum of 3 months before entering the trial and should continue with birth control for 1 month after the last dose of inhaled interferon-β (IFN-β1a)/matching placebo. In addition to the highly effective method of contraception (except for the practice of total sexual abstinence), a condom (in United Kingdom with spermicides) should be used by the male partner for sexual intercourse from randomisation (Visit 2) and for 1 month after the last dose of inhaled IFN-β1a/matching placebo to prevent pregnancy Women not of childbearing potential are defined as women who are either permanently sterilised (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), or who are postmenopausal. Women will be considered post-menopausal if they have been amenorrhoeic for 12 months prior to the planned date of randomisation without an alternative medical cause. The following age specific requirements apply: women <50 years old will be considered post-menopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatment and if follicle stimulating hormone (FSH) levels are in the postmenopausal range; women ≥50 years old will be considered post-menopausal if they have been amenorrhoeic for 12 months or more following cessation of all exogenous hormonal treatment. If, in the setting of the pandemic, the use of an acceptable birth control method is not possible, the decision to enrol a woman of childbearing potential should be based on the benefit-risk for the patient, which should be discussed with the patient at the time of the informed consent. Exclusion Criteria: Evidence of ongoing SARS-CoV-2 infection for more than 3 weeks, confirmed by a validated molecular assay or validated antigen assay Non-invasive ventilation continuous positive airway pressure/bilevel positive airway pressure (CPAP/BiPAP) or high-flow nasal oxygen therapy (WHO OSCI score of 5) Endotracheal intubation and invasive mechanical ventilation (WHO OSCI score of ≥6) or admission to intensive care Previous SARS-CoV-2 infection confirmed by a validated molecular assay or validated antigen assay Any condition, including findings in the patients' medical history or in the pre-randomisation study assessments that in the opinion of the Investigator, constitute a risk or a contraindication for the participation of the patient into the study or that could interfere with the study objectives, conduct or evaluation Participation in previous clinical trials of SNG001 Current or previous participation in another clinical trial where the patient has received a dose of an Investigational Medicinal Product containing small molecules within 30 days or 5 half-lives (whichever is longer) prior to entry into this study or containing biologicals within 3 months prior to entry into this study Inability to use a nebuliser with a mouthpiece Inability to comply with the requirements for storage conditions of study medication in the home setting History of hypersensitivity to natural or recombinant IFN-β or to any of the excipients in the drug preparation Females who are breast-feeding, lactating, pregnant or intending to become pregnant.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: SNG001<br>SNG001 via inhalation using Ultra device, once a day for 14 days | Drug: SNG001<br>* SNG001 nebuliser solution, 2 syringes each containing 0.65 mL once a day<br>|
| Placebo Comparator: Placebo<br>Placebo via inhalation using Ultra device, once a day for 14 days | Drug: Placebo<br>* Placebo nebuliser solution, 2 syringes each containing 0.65 mL solution containing excipients of the SNG001 solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Hospital Discharge | The time to hospital discharge in patients with moderate COVID-19 after administration of SNG001 compared to placebo was evaluated. | Day 28 | 
| Time to Recovery | Recovery in patients with moderate COVID-19 after administration of SNG001 compared to placebo by time to recovery was evaluated. | Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Who Progressed to Severe Disease or Death | 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. | Until Day 35 | 
| Number of Patients Who Were Intubated or Who Died | 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. | Until Day 35 | 
| Number of Patients Who Died Within 35 Days of First Dose | Patients who died within 35 days of first dose of study intervention were calculated. | Until Day 35 of first dose | 
| Cumulative Number of Patients Who Were Discharged From Hospital | The efficacy of SNG001 compared to placebo in patients with moderate COVID-19 was assessed by hospital discharge on given days. | Days 7, 14, 21 and 28 | 
| Cumulative Number of Patients With Recovery | 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. | Days 7, 14, 21 and 28 | 
| Improvement Based on Entire WHO OSCI Score | 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. | Until Day 35 | 
| Change From Baseline in Total Score According to the Breathlessness, Cough and Sputum Scale (BCSS) | 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. | Baseline to Day 15 | 
| Change From Baseline in National Early Warning Score (NEWS2) During the Hospitalisation Period | 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. | Day 1 until Day 28 | 
| Number of Patients With Presence of COVID-19 Symptoms Based on Daily Assessment | 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. | Day 1 until Day 90 | 
| Number of Patients With Limitations of Usual Activities Based on Daily Assessment | 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). | Day 1 until Day 35 | 
| Quality of Life Measured Using EuroQol 5-dimension 5-level (EQ-5D-5L) | 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. | Day 0, Day 7, Day 15, Day 28, Day 60 and Day 90 | 
| General Anxiety Disorder 7 Questionnaire (GAD-7) Total Score | 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. | Day 15, Day 28, Day 60 and Day 90 | 
| Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-FS [Version 4]) Total Score | 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. | Day 15, Day 28, Day 60 and Day 90 | 
| Patient Health Questionnaire-9 (PHQ-9) Total Score | 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. | Day 15, Day 28, Day 60 and Day 90 | 
| Overall Pain Severity as Measured by Brief Pain Inventory Composite Scores | 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. | Day 15, Day 28, Day 60 and Day 90 | 
| Number of Patients With Adverse Events (AEs) and Serious Adverse Events (SAEs) | 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. | From the day informed consent is obtained until 28 days after the last administration of the study medication (Day 90) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Coronavirus disease-2019 (COVID-19), Interferon beta