|E.1 Medical condition or disease under investigation
|Medical condition(s) being investigated
|Medical condition in easily understood language
|Lung disease caused by the new coronavirus
|Diseases [C] - Virus Diseases [C02]
|E.1.2 Medical condition or disease under investigation
|System Organ Class
|10021881 - Infections and infestations
|Condition being studied is a rare disease
|E.2 Objective of the trial
|Main objective of the trial
|To evaluate recovery in patients with moderate COVID-19 after administration of SNG001 compared to placebo.
|Secondary objectives of the trial
|To evaluate the efficacy of SNG001 compared to placebo in patients with moderate COVID-19, using a range of endpoints.
To assess the general safety and tolerability of SNG001 compared to placebo when administered to patients with moderate COVID-19.
To evaluate the pharmacokinetics (PK) of SNG001 in patients with moderate COVID-19.
|Trial contains a sub-study
|Principal inclusion criteria
|1. Male or female, ≥18 years of age at the time of consent.
2. Admitted to hospital due to the severity of their COVID-19.
3. 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.
4. Require oxygen therapy via nasal prongs or mask (WHO OSCI score of 4).
5. Provided informed consent.
6. Female patients must be ≥1 year post-menopausal, surgically sterile, or using a highly effective method of contraception. Acceptable highly effective methods of contraception include;
• bilateral tubal occlusion
• intrauterine device (provided coils are copper-banded)
• levonorgestrel intrauterine system (e.g., Mirena™)
• medroxyprogesterone injections (e.g., Depo-Provera™)
• etonogestrel implants (e.g., Implanon™, Norplan™)
• normal and low dose combined oral pills
• norelgestromin/ ethinylestradiol transdermal system
• intravaginal device (e.g., ethinylestradiol and etonogestrel), desogestrel (e.g., Cerazette™)
• total sexual abstinence (defined as refraining from heterosexual intercourse)
• vasectomised sexual partner.
Women of childbearing 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 IFN-β1a/matching placebo. In addition to the highly effective method of contraception (except for the practice of total sexual abstinence), a condom (in UK 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.
7. 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 would 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 would 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.
|Principal exclusion criteria
|1. Evidence of ongoing SARS-CoV-2 infection for more than 3 weeks, confirmed by a validated molecular assay or validated antigen assay.
2. Non-invasive ventilation (CPAP / BiPAP) or high-flow nasal oxygen therapy (WHO OSCI score of 5).
3. Endotracheal intubation and invasive mechanical ventilation (WHO OSCI score of ≥6)) or admission to intensive care.
4. Previous SARS-CoV-2 infection confirmed by a validated molecular assay or validated antigen assay.
5. 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.
6. Participation in previous clinical trials of SNG001.
7. 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.
8. Inability to use a nebuliser with a mouthpiece.
9. Inability to comply with the requirements for storage conditions of study medication in the home setting.
10. History of hypersensitivity to natural or recombinant IFN-β or to any of the excipients in the drug preparation.
11. Females who are breast-feeding, lactating, pregnant or intending to become pregnant.
|E.5 End points
|Primary end point(s)
|Time to hospital discharge, defined by the WHO OSCI score of 2 or below, with no rebound at subsequent assessments.
Time to recovery, where recovery is defined as the WHO OSCI score of 1 or below, with no rebound at subsequent assessments.
|Timepoint(s) of evaluation of this end point
|WHO OSCI assessments will be conducted daily between day 1 and day 35. Time to recovery will be assessed over the first 28 days of the study period. The WHO OSCI assessments after day 28 will be used to assess relapse only.
|Secondary end point(s)
|Key Secondary Endpoints:
a. Progression to severe disease or death, defined by the WHO OSCI score of 5 or above within 35 days of first dose (or randomisation date if the patient is not dosed).
b. Progression to intubation or death, defined by the WHO OSCI score of 6 or above within 35 days of first dose (or randomisation date if the patient is not dosed).
c. Death within 35 days of first dose (or randomisation date if the patient is not dosed).
a. Recovery, where recovery is defined as the WHO OSCI score of 1 or below, with no rebound at subsequent assessments, at Days 7, 14, 21 and 28.
b. Hospital discharge by Days 7, 14, 21 and 28.
c. Improvement across the entire WHO OSCI by Days 7, 14, 21 and 28.
d. Changes in breathlessness, cough and sputum scale (BCSS) score during the study period, including disaggregated breathlessness and cough scores.
e. Changes in National Early Warning Score 2 (NEWS2) during the hospitalisation period.
f. Daily assessment of COVID-19 symptoms and limitation of usual activities.
g. Quality of life measured using EQ-5D-5L.
h. Long-COVID-19 symptoms.
i. Safety and tolerability – vital signs, AEs, concomitant medications, and immunogenicity.
Serum PK parameters of SNG001 (maximum serum concentration
[Cmax], time to maximum serum concentration [Tmax], area under the serum concentration-time curve [AUC]).
|Timepoint(s) of evaluation of this end point
|Key secondary endpoints
Progression to severe disease or death will be assessed using all post-baseline WHO OSCI assessments up to day 28.
Time to hospital discharge will be assessed over the first 28 days of the study period. The WHO OSCI assessments after day 28 will be used to assess relapse only.
For Secondary endpoints the timepoints for evaluation are stated in the endpoint wording as per questions E5-2.
|E.6 and E.7 Scope of the trial
|Scope of the trial
|Trial type and phase
|Human pharmacology (Phase I)
|First administration to humans
|Other trial type description
|Therapeutic exploratory (Phase II)
|Therapeutic confirmatory (Phase III)
|Therapeutic use (Phase IV)
|E.8 Design of the trial
| Comparator of controlled trial
|Other medicinal product(s)
|Number of treatment arms in the trial
The trial involves single site in the Member State concerned
| The trial involves multiple sites in the Member State concerned
|Number of sites anticipated in Member State concerned
|The trial involves multiple Member States
|Number of sites anticipated in the EEA
|E.8.6 Trial involving sites outside the EEA
|Trial being conducted both within and outside the EEA
|Trial being conducted completely outside of the EEA
|If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
|Trial has a data monitoring committee
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|E.8.9 Initial estimate of the duration of the trial
|In the Member State concerned years
|In the Member State concerned months
|In the Member State concerned days
|In all countries concerned by the trial years
|In all countries concerned by the trial months
|In all countries concerned by the trial days