Study to Assess Efficacy and Safety of Inhaled Interferon-β Therapy for COVID-19

COVID-19 Clinical Trial

— SPRINTER  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04732949
• Other study ID #: SG018
• Secondary ID: 2020-004743-83
• Status: Completed
• Phase: Phase 3
• Start date: January 12, 2021
• Est. completion date: February 10, 2022

Study information

• Verified date: January 2021
• Source: Synairgen Research Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 623
• Est. completion date: February 10, 2022
• Est. primary completion date: December 15, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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-ß (IFN-ß1a)/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-ß1a/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-ß or to any of the excipients in the drug preparation

• Females who are breast-feeding, lactating, pregnant or intending to become pregnant.

Related Conditions & MeSH terms

• Coronavirus Infections
• COVID-19
• Severe Acute Respiratory Syndrome
• Severe Acute Respiratory Syndrome Coronavirus 2

Intervention

Drug:
• SNG001
SNG001 nebuliser solution, 2 syringes each containing 0.65 mL once a day
• Placebo
Placebo nebuliser solution, 2 syringes each containing 0.65 mL solution containing excipients of the SNG001 solution

Locations

Country	Name	City	State
Argentina	Hospital Universitario Austral	Buenos Aires
Argentina	Hospital Militar Central Cirujano Mayor Dr. Cosme Argerich	Ciudad Autónoma De Buenos Air	Buenos Aires
Argentina	Hospital Papa Francisco - Hosp	Salta
Belgium	UZ Brussel - Campus Jette - In	Brussel
Belgium	Centre Hospitalier Universitai	Bruxelles
Belgium	AZ Groeninge	Kortrijk	West-Vlaanderen
Belgium	CHR de la Citadelle - Site Cit	Liège
Belgium	CHU de Liège - Domaine Univers	Liège
Brazil	Instituto de Pesquisa Clínica	Campinas	São Paulo
Brazil	Clínica SUPERA	Chapeco	Santa Catarina
Brazil	Sociedade Literaria e Caritativa Santo Agostinho	Criciúma	Santa Catarina
Brazil	Instituto Mederi de Pesquisa e Saúde	Passo Fundo	Rio Grande Do Sul
Brazil	Hospital Moinhos de Vento	Porto Alegre	Rio Grande Do Sul
Brazil	Fundacao Faculdade Regional de	São José do Rio Preto	São Paulo
Colombia	Clinica de la Costa	Barranquilla
Colombia	Clinica de la Mujer	Bogotá	Cundinamarca
Colombia	FOSCAL	Bucaramanga	Santander
France	CHU d'Angers	Angers	Pays-de-la-Loire
France	CHU de Grenoble - Hôpital Albe	La Tronche
France	CHU De Nantes - Infectious Dis	Nantes	Loire-Atlantique
France	CHU Saint Antoine - Infectious	Paris
France	Hopital Bichat - Infectious Di	Paris
France	Hôpital Européen Georges-Pompi	Paris
Germany	Universitätsklinikum Mannheim	Mannheim
Germany	RoMed Medical Center Rosenheim	Rosenheim	Bayern
Germany	Krankenhaus Bethanien gGmbH	Solingen
India	Oriion Citicare Super Speciality Hospital - Intern	Aurangabad	Maharashtra
India	Bangalore Medical College and Research Institute	Bangalore	Karnataka
India	MS Ramaiah Medical College and Hospital	Bangalore	Karnataka
India	Post Graduate Institute of Medical Education & Research, Chandigarh	Chandigarh	Punjab
India	Saveetha Medical College & Hospital	Chennai
India	Fortis Hospital Mulund - Inter	Mumbai	Maharashtra
India	Government Medical College Nag	Nagpur	Maharashtra
India	Suyog Hospital	Nashik	Maharashtra
India	Vishwa Raj Hospital	Pune	Maharashtra
India	Unity Hospital	Surat	Gujarat
India	Rhythm Heart Institute	Vadodara	Gujarat
India	King George Hospital	Visakhapatnam	Andhra Pradesh
India	Acharya Vinoba Bhave Rural Hos	Wardha	Maharashtra
Israel	Assuta Ashdod University Hospi	Ashdod	HaDarom
Israel	Rambam Health Care Campus	Haifa
Israel	Ziv Medical Center	Safed
Israel	The Chaim Sheba Medical Center	Tel Hashomer
Israel	Sourasky Tel Aviv Medical Cent	Tel-Aviv
Israel	Assaf Harofeh Medical Center	Zerifin
Italy	Azienda Ospedaliera Nazionale	Alessandria
Italy	PO A.Manzoni di Lecco, ASST Le	Lecco
Italy	Azienda Ospedaliera Ospedale N	Milano
Italy	Ospedale Luigi Sacco, AO-PU	Milano
Italy	Azienda Socio Sanitaria Territ	Monza	Lombardia
Italy	AOU Federico II - Malattie Inf	Napoli
Italy	IRCCS Policlinico San Matteo	Pavia
Italy	AOU Pisana	Pisa
Italy	Città della Salute e della Scienza	Torino
Mexico	Hospital General de Culiacan D	Culiacan	Sinaloa
Mexico	EME RED Hospitalaria - COVID-1	Merida	Yucatán
Mexico	Hospital General Regional O´Hu	Merida	Yucatán
Mexico	Fundación Santos y de la Garza Evia, I.B.P	Monterrey	Nuevo León
Mexico	Clínica Sociedad Española de Beneficencia	Veracruz
Netherlands	Ziekenhuis St Jansdal	Harderwijk	Gelderland
Netherlands	Gelre Ziekenhuis Zutphen	Zutphen	Gelderland
Netherlands	Isala Klinieken	Zwolle	Overijssel
Portugal	Hospital Garcia da Orta, E.P.E	Almada	Lisboa
Portugal	Hospital de Braga	Braga
Portugal	Hospital da Senhora de Oliveir	Guimarães
Portugal	Centro Hospitalar de Entre Dou	Rodrigues
Portugal	C.H. de Vila Nova de Gaia/Espi	Vila Nova de Gaia	Porto
Romania	Sp. Cl. de Boli Infectioase si	Bucuresti
Romania	Spitalul Universitar de Urgent	Bucuresti
Romania	Spitalul Clinic de Boli Infect	Craiova
Romania	Sp. Clinic Boli Infectioase si	Timisoara	Timis
Serbia	University Clinical Center of Serbia	Belgrade
Serbia	Clinical Center Kragujevac, Cl	Kragujevac
Serbia	Clinical Center Nis	Nis	Nišavski Okrug
Serbia	Clinical Center of Vojvodina	Novi Sad	Vojvodina
Serbia	The Institute for Pulmonary Di	Sremska Kamenica
Spain	Hospital Santa Creu i Sant Pau	Barcelona
Spain	CHU A Coruña	Madrid	A Coruña
Spain	H.Clinico San Carlos	Madrid
Spain	Hospital Universitario Infanta	Madrid
Spain	Hospital Universitario Ramón y	Madrid
Spain	Hospital Universitario Son Esp	Palma De Mallorca	Baleares
Spain	Hospital Universitario de Puer	Puerto Real	Cádiz
Spain	Hospital Universitario de Sala	Salamanca
Spain	H U Nuesta Señora de Valme - I	Sevilla
Spain	Hospital Universitario Mutua d	Terrassa	Barcelona
United Kingdom	Queen Elizabeth Hospital Birmingham	Birmingham
United Kingdom	The Royal Bournemouth & Christ	Bournemouth
United Kingdom	University Hospital of North D	Durham
United Kingdom	Royal Devon & Exeter Hospital	Exeter
United Kingdom	Frimley Park Hospital	Frimley	Surrey
United Kingdom	Glasgow Royal Infirmary	Glasgow
United Kingdom	Churchill Hospital	Headington	Oxfordshire
United Kingdom	Hull Royal Infirmary	Hull, North Humberside	East Riding Of Yorkshire
United Kingdom	Glenfield Hospital	Leicester
United Kingdom	Guy's Hospital	London
United Kingdom	University Hospital Lewisham	London
United Kingdom	North Manchester General Hospi	Manchester
United Kingdom	The James Cook University Hosp	Middlesbrough
United Kingdom	Newcastle University - Institute of Cellular Medicine (ICM)	Newcastle	England
United Kingdom	Nottingham University Hospital	Nottingham
United Kingdom	Plymouth Hospitals NHS Trust	Plymouth
United Kingdom	Wexham Park Hospital	Slough	Bracknell Forest
United Kingdom	Southampton General Hospital	Southampton	Hampshire
United Kingdom	Morriston Hospital Swansea NHS	Swansea
United Kingdom	University Hospital of Wales	Swansea
United States	PharmaTex Research, LLC	Amarillo	Texas
United States	Henry Ford Health System	Detroit	Michigan
United States	University of Minnesota	Minneapolis	Minnesota
United States	Icahn School of Medicine at Mo	New York	New York
United States	Professional Health Care of Pi	Saint Petersburg	Florida
United States	The University of Arizona Medi	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Synairgen Research Ltd.

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Brazil,  Colombia,  France,  Germany,  India,  Israel,  Italy,  Mexico,  Netherlands,  Portugal,  Romania,  Serbia,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to Hospital Discharge	The time to hospital discharge in patients with moderate COVID-19 after administration of SNG001 compared to placebo was evaluated.	Day 28
Primary	Time to Recovery	Recovery in patients with moderate COVID-19 after administration of SNG001 compared to placebo by time to recovery was evaluated.	Day 28
Secondary	Number of Patients Who Progressed to Severe Disease or Death	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.	Until Day 35
Secondary	Number of Patients Who Were Intubated or Who Died	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.	Until Day 35
Secondary	Number of Patients Who Died Within 35 Days of First Dose	Patients who died within 35 days of first dose of study intervention were calculated.	Until Day 35 of first dose
Secondary	Cumulative Number of Patients Who Were Discharged From Hospital	The efficacy of SNG001 compared to placebo in patients with moderate COVID-19 was assessed by hospital discharge on given days.	Days 7, 14, 21 and 28
Secondary	Cumulative Number of Patients With Recovery	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.	Days 7, 14, 21 and 28
Secondary	Improvement Based on Entire WHO OSCI Score	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.	Until Day 35
Secondary	Change From Baseline in Total Score According to the Breathlessness, Cough and Sputum Scale (BCSS)	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.	Baseline to Day 15
Secondary	Change From Baseline in National Early Warning Score (NEWS2) During the Hospitalisation Period	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.	Day 1 until Day 28
Secondary	Number of Patients With Presence of COVID-19 Symptoms Based on Daily Assessment	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.	Day 1 until Day 90
Secondary	Number of Patients With Limitations of Usual Activities Based on Daily Assessment	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).	Day 1 until Day 35
Secondary	Quality of Life Measured Using EuroQol 5-dimension 5-level (EQ-5D-5L)	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.	Day 0, Day 7, Day 15, Day 28, Day 60 and Day 90
Secondary	General Anxiety Disorder 7 Questionnaire (GAD-7) Total Score	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.	Day 15, Day 28, Day 60 and Day 90
Secondary	Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-FS [Version 4]) Total Score	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.	Day 15, Day 28, Day 60 and Day 90
Secondary	Patient Health Questionnaire-9 (PHQ-9) Total Score	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.	Day 15, Day 28, Day 60 and Day 90
Secondary	Overall Pain Severity as Measured by Brief Pain Inventory Composite Scores	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".	Day 15, Day 28, Day 60 and Day 90
Secondary	Number of Patients With Adverse Events (AEs) and Serious Adverse Events (SAEs)	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.	From the day informed consent is obtained until 28 days after the last administration of the study medication (Day 90)