Clinical trial NCT04732949: Study to Assess Efficacy and Safety of Inhaled Interferon-β Therapy for COVID-19
Official title: A Randomised, Double-blind, Placebo-controlled, Phase III Trial to Determine the Efficacy and Safety of Inhaled SNG001 for the Treatment of Patients Hospitalised Due to Moderate COVID-19
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Severe Acute Respiratory Syndrome Coronavirus 2
COVID-19
Keywords: Coronavirus disease-2019 (COVID-19)
Interferon beta
Lead sponsor: Synairgen Research Ltd.
Sponsor class: INDUSTRY
First posted: 2021-02-01
Enrollment: 623
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

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