Plain English Summary
Background and study aims
COVID-19 is a condition caused by the coronavirus (called SARS-CoV-2) that was first identified in late 2019. This virus can infect the respiratory (breathing) system. Some people do not have symptoms but can carry the virus and pass it on to others. People who have developed the condition may develop a fever and/or a continuous cough among other symptoms. This can develop into pneumonia. Pneumonia is a chest infection where the small air pockets of the lungs, called alveoli, fill with liquid and make it more difficult to breathe.
In 2020, the virus has spread to many countries around the world and neither a vaccine against the virus or specific treatment for COVID-19 has yet been developed. As of March 2020, it is advised that people minimize travel and social contact, and regularly wash their hands to reduce the spread of the virus.
Groups who are at a higher risk from infection with the virus, and therefore of developing COVID-19, include people aged over 70 years, people who have long-term health conditions (such as asthma or diabetes), people who have a weakened immune system and people who are pregnant. People in these groups, and people who might come into contact with them, can reduce this risk by following the up-to-date advice to reduce the spread of the virus.
There is currently no vaccine to prevent infection with SARS-CoV-2 and no therapeutic agent to treat COVID-19. This clinical trial is designed to evaluate the potential of brensocatib (INS1007) as a novel therapy for the treatment of adult patients hospitalized with COVID-19.
Who can participate?
Persons over 16 years who have been admitted to hospital as an inpatient, and have laboratory-confirmed SARS-CoV-2 infection.
What does the study involve?
Participants will be randomised to receive brensocatib or placebo 25mg orally once daily for 28 days.
What are the possible benefits and risks of participating?
Brensocatib is an un-licensed medicine but it’s already been used in clinical trials. Trials with healthy people and those with lung conditions (with over 250 people involved) showed that the medicine was generally well tolerated by people in the trial. The most common side effects reported were cough, increased phlegm, headache and breathlessness. These are common symptoms for people with lung conditions and they were also reported frequently by people taking the placebo tablets. Two side effects that we know are possible with this medicine are thickening of the skin and inflammation of the gums, both of which happen rarely. (added 21/05/2020)
Where is the study run from?
Ninewells Hospital and Medical School (UK)
When is the study starting and how long is it expected to run for?
March 2020 to December 2020
Who is funding the study?
Insmed Incorporated (USA)
Who is the main contact?
Unfortunately, this study is not recruiting public volunteers at this time. This is because the research isn’t ready for volunteers yet or the researchers are directly identifying volunteers in certain areas or hospitals. Please do not contact the research team as they will not be able to respond. For more information about COVID-19 research, visit the Be Part of Research homepage. (added 21/05/2020)
Trial website
Contact information
Type
Public
Primary contact
Mrs Margaret Band
ORCID ID
Contact details
Taydside Clinical Trials Unit
TASC
Level 3
Ninewells Hospital and Medical School
Dundee
DD1 9SY
United Kingdom
+44 (0)1382 383097
m.band@dundee.ac.uk
Type
Scientific
Additional contact
Prof James Chalmers
ORCID ID
Contact details
Division of Cardiovascular Medicine
Level 5
Ninewells Hospital and Medical School
Dundee
DD1 9SY
United Kingdom
+44 (0)1382 383642
j.chalmers@dundee.ac.uk
Additional identifiers
EudraCT number
2020-001643-13
ClinicalTrials.gov number
Nil known
Protocol/serial number
01.01.20, IRAS 281986, CPMS 45682
Study information
Scientific title
A randomised double-blind placebo-controlled trial of brensocatib (INS1007) in patients with severe COVID-19
Acronym
STOP-COVID19
Study hypothesis
Treatment with brensocatib in addition to standard care will be superior to standard care alone in achieving improved clinical status in patients initially hospitalised with COVID-19.
Ethics approval
Approved 20/05/2020, Scotland A Research Ethics Committee (Research Ethics Service, 2nd Floor Waverley Gate, 2-4 Waterloo Place, Edinburgh, EH1 3EG, UK; +44 (0131 465 5680; Manx.Neill@nhslothian.scot.nhs.uk), ref: 20/SS/0057
Study design
Multi-centre randomized double-blind placebo-controlled parallel-group trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Condition
COVID-19 (SARS-CoV-2 infection)
Intervention
Participants will be randomised to receive brensocatib or placebo 25 mg orally once daily for 28 days.
Randomisation performed using an interactive web-based randomisation system (added 21/05/2020).
Intervention type
Drug
Phase
Phase III
Drug names
Brensocatib (INS1007)
Primary outcome measure
Participant clinical status (on a 7-point ordinal scale); up to day 29
Secondary outcome measures
1. Clinical Severity: Time to an improvement of one category from admission using 7-point ordinal scale; daily whilst in hospital
2. Participant clinical status on 7-point ordinal scale; Days 3, 5, 8, 11, 15 and 29
3. Mean change in the 7-point ordinal scale;Baseline to days 3, 5, 8, 11, 15 and 29
4. National Early Warning Score (NEWS): Time to discharge or to a NEWS of ≤ 2 and maintained for 24 hours, whichever occurs first; Daily whilst hospitalised. Change from baseline; Days 8, 15, 29
5. Oxygenation: Oxygen free days; 0-29 days. Incidence and duration of new oxygen use during the trial; 0 - 29 days
6. Mechanical Ventilation: Ventilator free days; 0-29 days. Incidence and duration of new mechanical ventilation use during the trial; 0-29 days
7. Hospitalisation: Duration of hospitalisation (days); Date of admission and discharge
8. Mortality: 28-day mortality; date of death
9. Safety:
9.1. Cumulative incidence of SAEs; 0-29 days
9.2. Discontinuation or temporary suspension of treatment; 0 - 29 days
9.3. Changes in white cell count, haemoglobin, platelets, creatinine, total bilirubin, ALT, and AST over time (hospitalised participants only); Days 0, 3, 5, 8, 11, 15, 29
9.4. Adverse events of special interest- hyperkeratosis, infections and dental complications; 0-29 days
10. Virologic efficacy (Tayside participants only):
10.1. Percent of participants with SARS-CoV-2 detectable in nasopharyngeal (NP) sample; Day 15 and day 29
10.2. Quantitative SARS-CoV-2 virus in NP samples; Day 15 and day 29
10.3. Neutrophil elastase and heparin binding protein measurement in blood; Days 0, 8, 15, 29
10.4. Neutrophil functional studies (NET formation, phagocytosis, elastase release, neutrophil proteomics; Days 0, 15, 29
11. Quality of life: EQ-5D-5L administered via telephone (if at home) or in person if still in hospital; day 29
Overall trial start date
30/03/2020
Overall trial end date
31/12/2020
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Aged ≥16 years
2. Laboratory-confirmed SARS-CoV-2 infection as determined by polymerase chain reaction (PCR), or other commercial or public health assay in any specimen < 96 h prior to randomization
3. Admitted to hospital as in-patient
4. Illness of any duration, and at least one of the following:
4.1. Radiographic infiltrates by imaging (e.g. chest x-ray, computed tomography (CT) scan) OR
4.2. Evidence of rales/crackles on physical examination OR
4.3. Peripheral capillary oxygen saturation (SpO2) ≤94% on room air prior to randomization OR
4.4. Requiring supplemental oxygen OR
4.5. Lymphocyte count <1 x 10(9) cells/l
5. Participant (or legally authorized representative) provides written informed consent
6. Able to take oral medication
7. Participant (or legally authorised representative) understands and agrees to comply with planned trial procedures
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
300
Participant exclusion criteria
1. Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >5x the upper limit of normal, result within 72 h of randomization (the result closest to randomization should be used if several results are available)
2. History of severe liver disease
3. Stage 4 severe chronic kidney disease or requiring dialysis (i.e. eGFR <30), result within 72 h of randomization (the result closest to randomization should be used if several results are available)
4. Absolute neutrophil count less than 1.0 x 10(9) cells/l within 72 h of randomization (the result closest to randomization should be used if several results are available)
5. Current treatment with itraconazole, ketoconazole, diltiazem or verapamil
6. Pregnant or breast feeding
7. Anticipated transfer to another hospital which is not a trial site within 24 hours
8. Allergy to brensocatib
9. Use of any investigational drug within 5 times the elimination half-life after the last trial dose or within 30 days, whichever is longer
Recruitment start date
20/05/2020
Recruitment end date
30/11/2020
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Ninewells Hospital and Medical School
NHS Tayside
Dundee
DD1 9SY
United Kingdom
Trial participating centre
Wishaw Hosptial
NHS Lanarkshire
Wishaw
ML2 0PD
United Kingdom
Trial participating centre
Raigmore Hospital
NHS Highland
Inverness
IV2 3UJ
United Kingdom
Sponsor information
Organisation
University of Dundee
Sponsor details
TASC
Level 3
Ninewells Hospital and Medical School
Dundee
DD1 9SY
United Kingdom
+44 (0)1382 383900
TASCgovernance@dundee.ac.uk
Sponsor type
University/education
Website
Organisation
NHS Tayside
Sponsor details
TASC
Level 3
Ninewells Hospital and Medical School
Dundee
DD1 9SY
United Kingdom
+44 (0)1382 383900
TASCgovernance@dundee.ac.uk
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Industry
Funder name
Insmed Incorporated
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Publication will include:
Peer reviewed scientific journals
Conference presentations
Publication on website
Dissemination to participants and public
IPD sharing statement:
All data generated or analysed during this study will be included in the subsequent results publication.
Intention to publish date
30/04/2021
Participant level data
Other
Basic results (scientific)
Publication list