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

• ClinicalTrials.gov Identifier: NCT04385095
• Recruitment Status: Completed
• First Posted: May 12, 2020
• Last Update Posted: January 4, 2023
• Sponsor: Synairgen Research Ltd.
• Information provided by (Responsible Party): Synairgen Research Ltd.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
SARS-CoV-2	Drug: SNG001; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 221 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment

Intervention 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 (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Double-blind
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: March 16, 2020
• Actual Primary Completion Date: February 17, 2021
• Actual Study Completion Date: November 16, 2021

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: SNG001; inhalation using the I-neb device.	Drug: SNG001; SNG001 via inhalation
Placebo Comparator: Placebo; inhalation using the I-neb device.	Drug: Placebo; Placebo via inhalation

Outcome Measures

Primary Outcome Measures :

1. Ordinal Scale for Clinical Improvement [ Time Frame: Day 1 to Days 15 and 28 ]
   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)

Secondary Outcome Measures :

1. Progression to pneumonia (hospital setting only) [ Time Frame: Day 2 to Day 28 ]
   Progression to pneumonia as diagnosed by chest x-ray, if no pneumonia is present at time of enrolment
2. Progression to pneumonia (hospital setting only) [ Time Frame: Day 1 to Day 28 ]
   Evolution of pneumonia, as diagnosed by chest x-ray, if pneumonia is present at time of enrolment
3. Time to clinical improvement (hospital setting only) [ Time Frame: Time to hospital discharge OR Time to NEWS2 of ≤ 2 maintained for 24 hours ]
   Time to clinical improvement
4. National Early Warning Score 2 (NEWS2) assessment of acute-illness severity (hospital setting only) [ Time Frame: Day 1 to Day 28 ]
   NEWS2 assessment of acute-illness severity on a scale of 0 ( being well) up to 24 (requiring emergency response)
5. Changes in daily breathlessness, cough and sputum scale (BCSS) [ Time Frame: Day 1 to Day 28 (and Day 60 and 90 home setting only) ]
   Changes in daily breathlessness, cough and sputum scale (BCSS) on a scale of 0 (no symptoms) up to 4 (severe symptoms)
6. Safety and tolerability - blood pressure (hospital setting only) [ Time Frame: Day 1 to Day 15 ]
   Looking at blood pressure measured in mmHg
7. Safety and tolerability - heart rate [ Time Frame: Day 1 to Day 15 ]
   Looking at heart rate measured in beats per minute
8. Safety and tolerability - temperature [ Time Frame: Day 1 to Day 15 ]
   Looking at temperature measured in degrees Celsius
9. Safety and tolerability - respiratory rate (hospital setting only) [ Time Frame: Day 1 to Day 15 ]
   Looking at respiratory rate measure in breaths per minute
10. Safety and tolerability - oxygen saturation [ Time Frame: Day 1 to Day 15 ]
    Looking at oxygen levels measured in a %
11. Safety and tolerability - adverse events [ Time Frame: Day 1 to Day 28 ]
    Looking at adverse events (numbers and terms)
12. Safety and tolerability - concomitant medications [ Time Frame: Day 1 to Day 28 ]
    Looking at concomitant medications given during treatment
13. Time to clinical improvement (home setting only) [ Time Frame: Day 1 to Day 15 ]
    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
14. Time to improvement of COVID-19 symptoms (home setting only). [ Time Frame: Day 1 to Day 28 and Day 60 and 90 ]
    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)
15. Time to self-reported recovery (home setting only) [ Time Frame: Day 2 to Day 15 and Day 28, 60 and 90 ]
    Time to self-reported recover
16. Self-reported daily rating of overall feeling of wellness (home setting only). [ Time Frame: Day 1 to Day 28 and Day 60 and 90 ]
    Self-reported daily rating of overall feeling of wellness scale from 1 (the worst you can imagine) to 10 (the best you can imagine)
17. Quality of life measured using EQ-5D-5L (home setting only). [ Time Frame: Day 1 to Day 28 and Day 60 and 90 ]
    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
18. Virus clearance/load (if samples are available) [ Time Frame: Day 1 to Day 28 ]
    Time to virus clearance and viral load
19. Blood and sputum biomarkers (if samples are available). [ Time Frame: Day 1 to Day 28 ]
    Blood and sputum biomarkers
20. Contact with health services (home setting only) [ Time Frame: Day 1 to Day 28 ]
    Contact with health services
21. Consumption of antibiotics (home setting only) [ Time Frame: Day 1 to Day 28 ]
    Consumption of antibiotics
22. General Anxiety Disorder 7 (home setting only) [ Time Frame: Day 60 and 90 ]
    Assessment of anxiety - score of 0 (best) to 3 (worst)
23. Patient Health Questionnaire - 9 [ Time Frame: Day 60 and 90 ]
    Assessment of mental health - score of 0 (best) to 3 (worst)
24. FACIT Fatigue Scale [ Time Frame: Day 60 and 90 ]
    Assessment of Fatigue - score of 0 (best) to 4 (worst)
25. Nottingham Extended Activities of Daily Living Scale [ Time Frame: Day 60 and 90 ]
    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'

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. 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.

2. Male or female, ≥18 years of age (hospital setting) or ≥50 years of age (home setting) at the time of consent.

3. 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
4. Provide informed consent.
5. 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:

1. > 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.
2. ≥ 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).
3. 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.
4. 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.
5. Ventilated or in intensive care.
6. Inability to use a nebuliser with a mouthpiece.
7. History of hypersensitivity to natural or recombinant IFN-β or to any of the excipients in the drug preparation.
8. Females who are breast-feeding, lactating, pregnant or intending to become pregnant.

Contacts and Locations

Locations

United Kingdom

Belfast City Hospital

Belfast, United Kingdom, BT9 7AB

Queen Elizabeth Hospital,

Birmingham, United Kingdom, B15 2GW

Bradford Royal Infirmary

Bradford, United Kingdom, BD9 6RJ

Park and St Francis Surgery

Chandler's Ford, United Kingdom, SO53 4ST

Hull and East Yorkshire NHS Trust, Castle Hill Hospital,

Hull, United Kingdom, HU16 5JQ

Glenfield Hospital,

Leicester, United Kingdom, LE3 9QP

Wythenshawe Hospital

Manchester, United Kingdom, M23 9LT

City Campus of Nottingham University

Nottingham, United Kingdom, NG5 1PB

John Radcliffe Hospital

Oxford, United Kingdom, OX3 9DU

The Adam Practice

Poole, United Kingdom, BH15 2HX

The Virtual Team

Southampton, United Kingdom, SO16 6YD

University Hospital Southampton Nhs Foundation Trust

Southampton, United Kingdom, SO16 6YD

Oaks Healthcare

Waterlooville, United Kingdom, PO8 8DL

Sponsors and Collaborators

Synairgen Research Ltd.

Investigators

• Principal Investigator: Tom Wilkinson; Study Chief Investigator
• Principal Investigator: Nick Francis; Study Deputy Chief Investigator

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Monk PD, Marsden RJ, Tear VJ, Brookes J, Batten TN, Mankowski M, Gabbay FJ, Davies DE, Holgate ST, Ho LP, Clark T, Djukanovic R, Wilkinson TMA; Inhaled Interferon Beta COVID-19 Study Group. Safety and efficacy of inhaled nebulised interferon beta-1a (SNG001) for treatment of SARS-CoV-2 infection: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Respir Med. 2021 Feb;9(2):196-206. doi: 10.1016/S2213-2600(20)30511-7. Epub 2020 Nov 12.

Lee JS, Shin EC. The type I interferon response in COVID-19: implications for treatment. Nat Rev Immunol. 2020 Oct;20(10):585-586. doi: 10.1038/s41577-020-00429-3.

• Responsible Party: Synairgen Research Ltd.
• ClinicalTrials.gov Identifier: NCT04385095
• Other Study ID Numbers: SG016
• First Posted: May 12, 2020
• Last Update Posted: January 4, 2023
• Last Verified: January 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: No plan to share data

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Synairgen Research Ltd.:

COVID-19

Additional relevant MeSH terms:

Infections