Clinical trial NCT04385095: Trial of Inhaled Anti-viral (SNG001) for SARS-CoV-2 (COVID-19) Infection
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: SARS-CoV-2
Keywords: COVID-19
Lead sponsor: Synairgen Research Ltd.
Sponsor class: INDUSTRY
First posted: 2020-05-12
Enrollment: 221
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Ordinal Scale for Clinical Improvement
timeFrame: Day 1 to Days 15 and 28
Secondary outcomes:
measure: Progression to pneumonia (hospital setting only)
timeFrame: Day 2 to Day 28
measure: Progression to pneumonia (hospital setting only)
timeFrame: Day 1 to Day 28
measure: Time to clinical improvement (hospital setting only)
timeFrame: Time to hospital discharge OR Time to NEWS2 of ≤ 2 maintained for 24 hours
measure: National Early Warning Score 2 (NEWS2) assessment of acute-illness severity (hospital setting only)
timeFrame: Day 1 to Day 28
measure: Changes in daily breathlessness, cough and sputum scale (BCSS)
timeFrame: Day 1 to Day 28 (and Day 60 and 90 home setting only)
measure: Safety and tolerability - blood pressure (hospital setting only)
timeFrame: Day 1 to Day 15
measure: Safety and tolerability - heart rate
timeFrame: Day 1 to Day 15
measure: Safety and tolerability - temperature
timeFrame: Day 1 to Day 15
measure: Safety and tolerability - respiratory rate (hospital setting only)
timeFrame: Day 1 to Day 15
measure: Safety and tolerability - oxygen saturation
timeFrame: Day 1 to Day 15
measure: Safety and tolerability - adverse events
timeFrame: Day 1 to Day 28
measure: Safety and tolerability - concomitant medications
timeFrame: Day 1 to Day 28
measure: Time to clinical improvement (home setting only)
timeFrame: Day 1 to Day 15
measure: Time to improvement of COVID-19 symptoms (home setting only).
timeFrame: Day 1 to Day 28 and Day 60 and 90
measure: Time to self-reported recovery (home setting only)
timeFrame: Day 2 to Day 15 and Day 28, 60 and 90
measure: Self-reported daily rating of overall feeling of wellness (home setting only).
timeFrame: Day 1 to Day 28 and Day 60 and 90
measure: Quality of life measured using EQ-5D-5L (home setting only).
timeFrame: Day 1 to Day 28 and Day 60 and 90
measure: Virus clearance/load (if samples are available)
timeFrame: Day 1 to Day 28
measure: Blood and sputum biomarkers (if samples are available).
timeFrame: Day 1 to Day 28
measure: Contact with health services (home setting only)
timeFrame: Day 1 to Day 28
measure: Consumption of antibiotics (home setting only)
timeFrame: Day 1 to Day 28
measure: General Anxiety Disorder 7 (home setting only)
timeFrame: Day 60 and 90
measure: Patient Health Questionnaire - 9
timeFrame: Day 60 and 90
measure: FACIT Fatigue Scale
timeFrame: Day 60 and 90
measure: Nottingham Extended Activities of Daily Living Scale
timeFrame: Day 60 and 90
Other outcomes:
Locations:
city: Belfast
country: United Kingdom
facility: Belfast City Hospital
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital,
city: Bradford
country: United Kingdom
facility: Bradford Royal Infirmary
city: Chandler's Ford
country: United Kingdom
facility: Park and St Francis Surgery
city: Hull
country: United Kingdom
facility: Hull and East Yorkshire NHS Trust, Castle Hill Hospital,
city: Leicester
country: United Kingdom
facility: Glenfield Hospital,
city: Manchester
country: United Kingdom
facility: Wythenshawe Hospital
city: Nottingham
country: United Kingdom
facility: City Campus of Nottingham University
city: Oxford
country: United Kingdom
facility: John Radcliffe Hospital
city: Poole
country: United Kingdom
facility: The Adam Practice
city: Southampton
country: United Kingdom
facility: The Virtual Team
city: Southampton
country: United Kingdom
facility: University Hospital Southampton Nhs Foundation Trust
city: Waterlooville
country: United Kingdom
facility: Oaks Healthcare
Study officials:
affiliation: Study Chief Investigator
name: Tom Wilkinson
role: PRINCIPAL_INVESTIGATOR
affiliation: Study Deputy Chief Investigator
name: Nick Francis
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.