Trial of Inhaled Anti-viral (SNG001) for SARS-CoV-2 (COVID-19) Infection

Study Overview
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Brief Summary
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SNG001 is an inhaled drug that contains a antiviral protein called interferon beta (IFN-β). IFN-β in produced in the lungs during viral lung infections. It has been shown that older people and people with some chronic diseases have an IFN-β deficiency. Many viruses inhibit IFN-β as part of their strategy to evade the immune system. Addition of IFN-β in vitro protects lung cells from viral infection. IFN-β protects cells against the MERS and SARS coronaviruses (close relatives of SARS-CoV-2, the virus that causes COVID-19). SNG001 is an inhaled formulation of interferon beta-1a it is currently in Phase II clinical trials for COPD patients. Synairgen has conducted randomised placebo controlled clinical trials of SNG001 involving >200 asthma and COPD patients. These trials have shown that SNG001 has: been well tolerated during virus infections enhanced antiviral activity in the lungs (measured in sputum and blood samples) provided significant lung function benefit over placebo in asthma in two Phase II trials. Synairgen believes SNG001 could help prevent worsening or accelerate recovery of severe lower respiratory tract illness in COVID-19 patients. Patients who are in hospital or non-hospitalised but are a high risk groups (e.g. elderly or diabetics) will be invited to take part in the trial. The patient would receive either SNG001 or placebo once daily for 14 days. The severity of the patients condition would be recorded on a scale developed by the World Health Organisation and the patient would be asked questions about their breathlessness, cough and sputum every day, as well as assess their general medical condition and safety. The study will start as a Pilot phase where 100 patients will be randomised in the hospital setting and a 120 patients randomised in the home setting. Once each of the Pilot phases are complete, a Pivotal phase will be conducted. It is estimated that the size of each of the Pivotal phases (hospital and home) will be around 100 to 300 patients per arm. The actual number will be determined after the data review at the end of each of the Pilot phases. If SNG001 proves to be beneficial it would be a major breakthrough for the treatment of COVID-19.

Official Title
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A Randomised Double-blind Placebo-controlled Trial to Determine the Safety and Efficacy of Inhaled SNG001 (IFN-β1a for Nebulisation) for the Treatment of Patients With Confirmed SARS-CoV-2 Infection

Conditions
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SARS-CoV-2

Intervention / Treatment
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* Drug: SNG001
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A. Hospital setting: positive virus test for SARS-CoV-2 using RT-PCR, or positive point-of-care viral infection test in the presence of strong clinical suspicion of SARS-CoV-2 infection. B. Home setting: positive virus test for SARS-CoV-2 using a molecular assay e.g. RT-PCR in the presence of strong clinical suspicion of SARS-CoV-2 infection. Male or female, ≥18 years of age (hospital setting) or ≥50 years of age (home setting) at the time of consent. A. Hospital setting: patients admitted to hospital due to the severity of their COVID 19 disease OR B. Home setting: non-hospitalised patients from high-risk groups, defined as ≥65-years of age, or ≥50 years of age and with any of the following risk factors: Arterial hypertension Cardiovascular disease Diabetes mellitus Chronic lung disease Chronic kidney disease (eGFR <60 mL/min/1.73m2) Chronic liver disease Immunodeficiency due to a serious illness or medication Cerebrovascular disease Malignancy (except basal cell carcinoma) diagnosed in the last 5 years Body Mass Index ≥30 who present with clinical symptoms consistent with COVID-19: High temperature and/or New, continuous cough. Loss or change to sense of smell and/or taste Provide informed consent. A. Hospital setting: hospitalised female patients must be ≥1 year post-menopausal, surgically sterile, or using an acceptable method of contraception. B. Home setting: non-hospitalised female patients must be ≥1 year post-menopausal or surgically sterile. Exclusion Criteria: > 24 hours after confirmation of SARS-CoV-2 infection by a molecular assay e.g. RT-PCR test (hospital and home settings) or >24 hours after a positive point-of-care viral infection test (hospital setting only). This criterion does not apply to patients in the hospital setting who had their positive RT-PCR test for SARS-CoV-2 performed prior to hospitalisation. ≥ 8 days from onset of COVID-19 symptoms (cough and/or fever and/or loss or change to sense of smell and/or taste; home setting only). 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. Current or previous participation in another clinical trial where the patient has received a dose of an Investigational Medicinal Product (IMP) 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. Ventilated or in intensive care. Inability to use a nebuliser with a mouthpiece. 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
Interventional Model Description: Randomised double-blind placebo-controlled Pilot phase - 100 patients randomised in the hospital setting, 120 patients randomised in the home setting. Pivotal phase - estimated at an additional 100 to 300 patients per arm, but the actual number will be determined after the data review at the end of the Pilot phase
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: SNG001<br>inhalation using the I-neb device. | Drug: SNG001<br>* SNG001 via inhalation<br>|
| Placebo Comparator: Placebo<br>inhalation using the I-neb device. | Drug: Placebo<br>* Placebo via inhalation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ordinal Scale for Clinical Improvement | Change in condition measured using the Ordinal Scale for Clinical Improvement during the dosing period - minimum of 0 (patient is well) to a maximum of 8 (death) | Day 1 to Days 15 and 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression to pneumonia (hospital setting only) | Progression to pneumonia as diagnosed by chest x-ray, if no pneumonia is present at time of enrolment | Day 2 to Day 28 | 
| Progression to pneumonia (hospital setting only) | Evolution of pneumonia, as diagnosed by chest x-ray, if pneumonia is present at time of enrolment | Day 1 to Day 28 | 
| Time to clinical improvement (hospital setting only) | Time to clinical improvement | Time to hospital discharge OR Time to NEWS2 of ≤ 2 maintained for 24 hours | 
| National Early Warning Score 2 (NEWS2) assessment of acute-illness severity (hospital setting only) | NEWS2 assessment of acute-illness severity on a scale of 0 ( being well) up to 24 (requiring emergency response) | Day 1 to Day 28 | 
| Changes in daily breathlessness, cough and sputum scale (BCSS) | Changes in daily breathlessness, cough and sputum scale (BCSS) on a scale of 0 (no symptoms) up to 4 (severe symptoms) | Day 1 to Day 28 (and Day 60 and 90 home setting only) | 
| Safety and tolerability - blood pressure (hospital setting only) | Looking at blood pressure measured in mmHg | Day 1 to Day 15 | 
| Safety and tolerability - heart rate | Looking at heart rate measured in beats per minute | Day 1 to Day 15 | 
| Safety and tolerability - temperature | Looking at temperature measured in degrees Celsius | Day 1 to Day 15 | 
| Safety and tolerability - respiratory rate (hospital setting only) | Looking at respiratory rate measure in breaths per minute | Day 1 to Day 15 | 
| Safety and tolerability - oxygen saturation | Looking at oxygen levels measured in a % | Day 1 to Day 15 | 
| Safety and tolerability - adverse events | Looking at adverse events (numbers and terms) | Day 1 to Day 28 | 
| Safety and tolerability - concomitant medications | Looking at concomitant medications given during treatment | Day 1 to Day 28 | 
| Time to clinical improvement (home setting only) | Temperature ≤37.8 °C AND COVID-19 symptoms (breathing, cough, sputum, muscle aches, headache, fatigue, sore throat, loss or change to sense of smell and taste, rhinorrhoea and anorexia) all rated as absent or mild | Day 1 to Day 15 | 
| Time to improvement of COVID-19 symptoms (home setting only). | Time to improvement of COVID-19 symptoms (fever, breathing, cough, sputum, muscle aches, headache, fatigue, sore throat, loss or change to sense of smell and/or taste, rhinorrhoea and anorexia) | Day 1 to Day 28 and Day 60 and 90 | 
| Time to self-reported recovery (home setting only) | Time to self-reported recover | Day 2 to Day 15 and Day 28, 60 and 90 | 
| Self-reported daily rating of overall feeling of wellness (home setting only). | Self-reported daily rating of overall feeling of wellness scale from 1 (the worst you can imagine) to 10 (the best you can imagine) | Day 1 to Day 28 and Day 60 and 90 | 
| Quality of life measured using EQ-5D-5L (home setting only). | Quality of life measured using EQ-5D-5L - 5 questions where minimum score is 1 (best outcome) to 5 (worst outcome), visual analogue scale is also included for this 100 is best health you can imagine to 0 worst health you can imagine | Day 1 to Day 28 and Day 60 and 90 | 
| Virus clearance/load (if samples are available) | Time to virus clearance and viral load | Day 1 to Day 28 | 
| Blood and sputum biomarkers (if samples are available). | Blood and sputum biomarkers | Day 1 to Day 28 | 
| Contact with health services (home setting only) | Contact with health services | Day 1 to Day 28 | 
| Consumption of antibiotics (home setting only) | Consumption of antibiotics | Day 1 to Day 28 | 
| General Anxiety Disorder 7 (home setting only) | Assessment of anxiety - score of 0 (best) to 3 (worst) | Day 60 and 90 | 
| Patient Health Questionnaire - 9 | Assessment of mental health - score of 0 (best) to 3 (worst) | Day 60 and 90 | 
| FACIT Fatigue Scale | Assessment of Fatigue - score of 0 (best) to 4 (worst) | Day 60 and 90 | 
| Nottingham Extended Activities of Daily Living Scale | Assessment of activities of daily living - no score just tick the box that applies; 'Not at all', 'With help', 'On your own with difficulty' and 'On your own' | Day 60 and 90 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19