Study to Assess Efficacy and Safety of Inhaled Interferon-β Therapy for COVID-19
- Conditions
- Severe Acute Respiratory Syndrome Coronavirus 2COVID-19
- Interventions
- Drug: Placebo
- Registration Number
- NCT04732949
- Lead Sponsor
- Synairgen Research Ltd.
- Brief Summary
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
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 623
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Placebo via inhalation using Ultra device, once a day for 14 days SNG001 SNG001 SNG001 via inhalation using Ultra device, once a day for 14 days
- Primary Outcome Measures
Name Time Method Time to Hospital Discharge Day 28 The time to hospital discharge in patients with moderate COVID-19 after administration of SNG001 compared to placebo was evaluated.
Time to Recovery Day 28 Recovery in patients with moderate COVID-19 after administration of SNG001 compared to placebo by time to recovery was evaluated.
- Secondary Outcome Measures
Name Time Method Number of Patients Who Were Intubated or Who Died Until Day 35 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.
Patient Health Questionnaire-9 (PHQ-9) Total Score Day 15, Day 28, Day 60 and Day 90 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.
Number of Patients Who Progressed to Severe Disease or Death Until Day 35 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.
Number of Patients Who Died Within 35 Days of First Dose Until Day 35 of first dose Patients who died within 35 days of first dose of study intervention were calculated.
Cumulative Number of Patients Who Were Discharged From Hospital Days 7, 14, 21 and 28 The efficacy of SNG001 compared to placebo in patients with moderate COVID-19 was assessed by hospital discharge on given days.
Cumulative Number of Patients With Recovery Days 7, 14, 21 and 28 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.
Improvement Based on Entire WHO OSCI Score Until Day 35 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.
Change From Baseline in Total Score According to the Breathlessness, Cough and Sputum Scale (BCSS) Baseline to Day 15 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.Change From Baseline in National Early Warning Score (NEWS2) During the Hospitalisation Period Day 1 until Day 28 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.Quality of Life Measured Using EuroQol 5-dimension 5-level (EQ-5D-5L) Day 0, Day 7, Day 15, Day 28, Day 60 and Day 90 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.
General Anxiety Disorder 7 Questionnaire (GAD-7) Total Score Day 15, Day 28, Day 60 and Day 90 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.
Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-FS [Version 4]) Total Score Day 15, Day 28, Day 60 and Day 90 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.
Number of Patients With Presence of COVID-19 Symptoms Based on Daily Assessment Day 1 until Day 90 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.
Number of Patients With Limitations of Usual Activities Based on Daily Assessment Day 1 until Day 35 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).
Overall Pain Severity as Measured by Brief Pain Inventory Composite Scores Day 15, Day 28, Day 60 and Day 90 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".
Number of Patients With Adverse Events (AEs) and Serious Adverse Events (SAEs) From the day informed consent is obtained until 28 days after the last administration of the study medication (Day 90) 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.
Trial Locations
- Locations (112)
Instituto Mederi de Pesquisa e Saúde
🇧🇷Passo Fundo, Rio Grande Do Sul, Brazil
Hospital General de Culiacan D
🇲🇽Culiacan, Sinaloa, Mexico
Hospital General Regional O´Hu
🇲🇽Merida, Yucatán, Mexico
Hospital Moinhos de Vento
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
EME RED Hospitalaria - COVID-1
🇲🇽Merida, Yucatán, Mexico
Hospital Militar Central Cirujano Mayor Dr. Cosme Argerich
🇦🇷Ciudad Autónoma De Buenos Air, Buenos Aires, Argentina
AZ Groeninge
🇧🇪Kortrijk, West-Vlaanderen, Belgium
CHU De Nantes - Infectious Dis
🇫🇷Nantes, Loire-Atlantique, France
Rambam Health Care Campus
🇮🇱Haifa, Israel
The Chaim Sheba Medical Center
🇮🇱Tel Hashomer, Israel
UZ Brussel - Campus Jette - In
🇧🇪Brussel, Belgium
CHU de Liège - Domaine Univers
🇧🇪Liège, Belgium
Sociedade Literaria e Caritativa Santo Agostinho
🇧🇷Criciúma, Santa Catarina, Brazil
King George Hospital
🇮🇳Visakhapatnam, Andhra Pradesh, India
Unity Hospital
🇮🇳Surat, Gujarat, India
CHR de la Citadelle - Site Cit
🇧🇪Liège, Belgium
Clinica de la Mujer
🇨🇴Bogotá, Cundinamarca, Colombia
Bangalore Medical College and Research Institute
🇮🇳Bangalore, Karnataka, India
Post Graduate Institute of Medical Education & Research, Chandigarh
🇮🇳Chandigarh, Punjab, India
Saveetha Medical College & Hospital
🇮🇳Chennai, India
Rhythm Heart Institute
🇮🇳Vadodara, Gujarat, India
Instituto de Pesquisa Clínica
🇧🇷Campinas, São Paulo, Brazil
Acharya Vinoba Bhave Rural Hos
🇮🇳Wardha, Maharashtra, India
CHU d'Angers
🇫🇷Angers, Pays-de-la-Loire, France
Oriion Citicare Super Speciality Hospital - Intern
🇮🇳Aurangabad, Maharashtra, India
Centre Hospitalier Universitai
🇧🇪Bruxelles, Belgium
Clínica SUPERA
🇧🇷Chapeco, Santa Catarina, Brazil
MS Ramaiah Medical College and Hospital
🇮🇳Bangalore, Karnataka, India
Assuta Ashdod University Hospi
🇮🇱Ashdod, HaDarom, Israel
Clínica Sociedad Española de Beneficencia
🇲🇽Veracruz, Mexico
Hospital Garcia da Orta, E.P.E
🇵🇹Almada, Lisboa, Portugal
Sp. Clinic Boli Infectioase si
🇷🇴Timisoara, Timis, Romania
Fortis Hospital Mulund - Inter
🇮🇳Mumbai, Maharashtra, India
Clinical Center of Vojvodina
🇷🇸Novi Sad, Vojvodina, Serbia
Hospital de Braga
🇵🇹Braga, Portugal
Government Medical College Nag
🇮🇳Nagpur, Maharashtra, India
Ziekenhuis St Jansdal
🇳🇱Harderwijk, Gelderland, Netherlands
Gelre Ziekenhuis Zutphen
🇳🇱Zutphen, Gelderland, Netherlands
C.H. de Vila Nova de Gaia/Espi
🇵🇹Vila Nova de Gaia, Porto, Portugal
Sourasky Tel Aviv Medical Cent
🇮🇱Tel-Aviv, Israel
Clinical Center Nis
🇷🇸Nis, Nišavski Okrug, Serbia
CHU A Coruña
🇪🇸Madrid, A Coruña, Spain
Wexham Park Hospital
🇬🇧Slough, Bracknell Forest, United Kingdom
Vishwa Raj Hospital
🇮🇳Pune, Maharashtra, India
Assaf Harofeh Medical Center
🇮🇱Zerifin, Israel
Hospital da Senhora de Oliveir
🇵🇹Guimarães, Portugal
Spitalul Universitar de Urgent
🇷🇴Bucuresti, Romania
Sp. Cl. de Boli Infectioase si
🇷🇴Bucuresti, Romania
The Institute for Pulmonary Di
🇷🇸Sremska Kamenica, Serbia
Spitalul Clinic de Boli Infect
🇷🇴Craiova, Romania
Clinical Center Kragujevac, Cl
🇷🇸Kragujevac, Serbia
Southampton General Hospital
🇬🇧Southampton, Hampshire, United Kingdom
University Clinical Center of Serbia
🇷🇸Belgrade, Serbia
The Royal Bournemouth & Christ
🇬🇧Bournemouth, United Kingdom
University Hospital Lewisham
🇬🇧London, United Kingdom
Glasgow Royal Infirmary
🇬🇧Glasgow, United Kingdom
Glenfield Hospital
🇬🇧Leicester, United Kingdom
Nottingham University Hospital
🇬🇧Nottingham, United Kingdom
University Hospital of North D
🇬🇧Durham, United Kingdom
Plymouth Hospitals NHS Trust
🇬🇧Plymouth, United Kingdom
Morriston Hospital Swansea NHS
🇬🇧Swansea, United Kingdom
North Manchester General Hospi
🇬🇧Manchester, United Kingdom
Queen Elizabeth Hospital Birmingham
🇬🇧Birmingham, United Kingdom
Royal Devon & Exeter Hospital
🇬🇧Exeter, United Kingdom
Churchill Hospital
🇬🇧Headington, Oxfordshire, United Kingdom
Frimley Park Hospital
🇬🇧Frimley, Surrey, United Kingdom
The James Cook University Hosp
🇬🇧Middlesbrough, United Kingdom
University Hospital of Wales
🇬🇧Swansea, United Kingdom
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Isala Klinieken
🇳🇱Zwolle, Overijssel, Netherlands
Città della Salute e della Scienza
🇮🇹Torino, Italy
Hospital Universitario de Sala
🇪🇸Salamanca, Spain
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
The University of Arizona Medi
🇺🇸Tucson, Arizona, United States
Professional Health Care of Pi
🇺🇸Saint Petersburg, Florida, United States
PharmaTex Research, LLC
🇺🇸Amarillo, Texas, United States
Icahn School of Medicine at Mo
🇺🇸New York, New York, United States
Hospital Universitario Austral
🇦🇷Buenos Aires, Argentina
Hospital Papa Francisco - Hosp
🇦🇷Salta, Argentina
Fundacao Faculdade Regional de
🇧🇷São José do Rio Preto, São Paulo, Brazil
FOSCAL
🇨🇴Bucaramanga, Santander, Colombia
Clinica de la Costa
🇨🇴Barranquilla, Colombia
CHU de Grenoble - Hôpital Albe
🇫🇷La Tronche, France
CHU Saint Antoine - Infectious
🇫🇷Paris, France
Hôpital Européen Georges-Pompi
🇫🇷Paris, France
Hopital Bichat - Infectious Di
🇫🇷Paris, France
Universitätsklinikum Mannheim
🇩🇪Mannheim, Germany
Krankenhaus Bethanien gGmbH
🇩🇪Solingen, Germany
RoMed Medical Center Rosenheim
🇩🇪Rosenheim, Bayern, Germany
Suyog Hospital
🇮🇳Nashik, Maharashtra, India
Ziv Medical Center
🇮🇱Safed, Israel
Azienda Socio Sanitaria Territ
🇮🇹Monza, Lombardia, Italy
Azienda Ospedaliera Nazionale
🇮🇹Alessandria, Italy
PO A.Manzoni di Lecco, ASST Le
🇮🇹Lecco, Italy
Ospedale Luigi Sacco, AO-PU
🇮🇹Milano, Italy
Azienda Ospedaliera Ospedale N
🇮🇹Milano, Italy
AOU Federico II - Malattie Inf
🇮🇹Napoli, Italy
IRCCS Policlinico San Matteo
🇮🇹Pavia, Italy
AOU Pisana
🇮🇹Pisa, Italy
Fundación Santos y de la Garza Evia, I.B.P
🇲🇽Monterrey, Nuevo León, Mexico
Centro Hospitalar de Entre Dou
🇵🇹Rodrigues, Portugal
Hospital Universitario Son Esp
🇪🇸Palma De Mallorca, Baleares, Spain
Hospital Universitario Mutua d
🇪🇸Terrassa, Barcelona, Spain
Hospital Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Hospital Universitario Ramón y
🇪🇸Madrid, Spain
H.Clinico San Carlos
🇪🇸Madrid, Spain
H U Nuesta Señora de Valme - I
🇪🇸Sevilla, Spain
Hull Royal Infirmary
🇬🇧Hull, North Humberside, East Riding Of Yorkshire, United Kingdom
Newcastle University - Institute of Cellular Medicine (ICM)
🇬🇧Newcastle, England, United Kingdom
Hospital Universitario Infanta
🇪🇸Madrid, Spain
Hospital Universitario de Puer
🇪🇸Puerto Real, Cádiz, Spain
Guy's Hospital
🇬🇧London, United Kingdom