STOP-COVID19: Superiority Trial Of Protease Inhibition in COVID-19

NCT04817332 | Completed Phase 3 Results DMC FDA Drug

• 3 other identifiers: 01.01.202020-001643-13281986
• Study Type: interventional
• Target: 406
• Locations: 1 country
• Sites: 16

Brief Summary

COVID-19 is a respiratory disease caused by a novel coronavirus (SARS-CoV-2) and causes substantial morbidity and mortality. 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 host directed therapy for the treatment of adult patients hospitalized with COVID-19. The investigators hypothesise that Brensocatib, by blocking damaging neutrophil proteases, will reduce the incidence of acute lung injury and acute respiratory distress syndrome (ARDS) in patients with COVID-19, thereby resulting in improved clinical outcomes at day 15 and day 29, fewer days dependent on oxygen or mechanical ventilation, and shorter length of hospital stay. High rates of patients requiring mechanical ventilation and overwhelming intensive care unit capacity has been the major issue contributing to excess deaths in Italy and Spain during the pandemic and is likely to be a major issue in other countries such as the United Kingdom in the coming weeks. Treatments that could prevent the requirement for mechanical ventilation or shorten the duration of ICU stay by reducing the severity of ARDS are therefore the number 1 target for COVID19 therapy. The investigators recently conducted a large phase 2 study of Brensocatib in patients with bronchiectasis designed to test if treatment with Brensocatib could reduce infective exacerbations and reduce neutrophil elastase activity in the lung in bronchiectasis patients. The study met its primary endpoint of time to first exacerbation and key secondary endpoint of the frequency of exacerbations as well as showing marked reductions in neutrophil elastase concentrations in sputum. Participants will be randomised to receive Brensocatib or placebo 25mg orally once daily for 28 days.

Conditions

Covid19

Outcome Measures

Primary Outcomes (1)

• Comparison of Participant Clinical Status Between Treatment Arms

  To determine the participant clinical status on a 7-point ordinal scale, minimum value 1, maximum value 7. Higher values indicate a worse outcome: 1. Not hospitalised, no limitations on activities 2. Not hospitalised, limitation on activities; 3. Hospitalised, not requiring supplemental oxygen; 4. Hospitalised, requiring supplemental oxygen; 5. Hospitalised, on non-invasive ventilation or high flow oxygen devices; 6. Hospitalised, on invasive mechanical ventilation or Extracorporeal membrane oxygenation (ECMO) 7. Death.

  Up to 29 days

Secondary Outcomes (21)

• Improvement of One Category From Admission Using 7-point Ordinal Scale.

  Day 29

• Participant Clinical Status on 7-point Ordinal Scale

  Day 15

• Mean Change in the 7-point Ordinal Scale

  Baseline to days 3, 5, 8, 11 and 29

• Number of Participants Discharged or to a National Early Warning Score (NEWS) of Equal or Less Than 2 and Maintained for 24 Hours, Whichever Occurs First.

  Up to 29 days

• Change From Baseline of National Early Warning Score (NEWS).

  Baseline to day 15

Other Outcomes (8)

• Percent of Participants With SARS-CoV-2 Detectable in Nasopharyngeal Sample

  Day 15 and day 29

• Quantitative SARS-CoV-2 Virus in Nasopharyngeal Samples.

  Day 15 and day 29

• Neutrophil Elastase and Heparin Binding Protein Measurement in Blood

  Days 1, 8, 15, 29

Study Arms (2)

Brensocatib

EXPERIMENTAL

Brensocatib oral tablet, 25mg once per day for 28 days

Drug: Brensocatib

Placebo

PLACEBO COMPARATOR

Placebo oral tablet, 25mg once per day for 28 days

Drug: Placebo

Interventions

Brensocatib DRUG

Selective, competitive, and reversible inhibitor of DPP1

Also known as: INS1007

Brensocatib

Placebo DRUG

Matched placebo

Placebo

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female
• ≥16 years of age
• SARS-CoV-2 infection (clinically suspected+ or laboratory confirmed\*).
• Admitted to hospital as in-patient less than 96 hours prior to randomisation\^
• Illness of any duration, and at least one of the following:
• Radiographic infiltrates by imaging (e.g. chest x-ray, computed tomography (CT) scan) OR
• Evidence of rales/crackles on physical examination OR
• Peripheral capillary oxygen saturation (SpO2) ≤94% on room air prior to randomization OR
• Requiring supplemental oxygen. OR
• Lymphocyte count \<1 x 109 cells per litre (L)
• Participant (or legally authorized representative) provides written informed consent
• Able to take oral medication
• Participant (or legally authorised representative) understands and agrees to comply with planned trial procedures.
• Laboratory-confirmed: SARS-CoV-2 infection as determined by polymerase chain reaction (PCR), or other commercial or public health assay in any specimen \< 96 hours prior to randomization.
• Clinically suspected: in general, SARS-CoV-2 infection should be suspected when a patient presents with (i) typical symptoms (e.g. influenza-like illness with fever and muscle pain, or respiratory illness with cough and shortness of breath); and (ii) compatible chest X-ray findings (consolidation or ground-glass shadowing); and (iii) alternative causes have been considered unlikely or excluded (e.g. heart failure, influenza). However, the diagnosis remains a clinical one based on the opinion of the managing doctor

You may not qualify if:

• Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) \> 5 times the upper limit of normal, result within 72 hours of randomization (the result closest to randomization should be used if several results are available).
• History of severe liver disease
• Stage 4 severe chronic kidney disease or requiring dialysis (i.e. estimated Glomerular Filtration Rate \< 30), result within 72 hours of randomization (the result closest to randomization should be used if several results are available)
• Absolute neutrophil count less than 1.0 x 109 cells per L within 72 hours of randomization (the result closest to randomization should be used if several results are available)
• Current treatments with potent Cyp3A4 inducers/inhibitors (e.g Itraconazole, Ketoconazole, diltiazem, verapamil, phenytoin or rifampicin)
• HIV treatments - current treatment with protease/integrase inhibitors or non-nucleoside reverse transcriptase inhibitors\*
• Pregnant or breast feeding.
• Anticipated transfer to another hospital which is not a trial site within 24 hours.
• Allergy to Brensocatib
• Use of any investigational drug within five times of the elimination half-life after the last trial dose or within 30 days, whichever is longer. Co-enrolment with COVID-19 trials is allowed as per co-enrolment agreements and/or individual decision by the Chief Investigator.
• Women of child-bearing potential must be willing to have pregnancy testing prior to trial entry.
• \*The Liverpool HIV checker (https://www.hiv-druginteractions.org/checker) should be used to check for any HIV drug interactions. Simvastatin could be used as a surrogate for Brensocatib as it metabolised similarly by CYP 3A4 pathway.

Sponsors & Collaborators

• University of Dundee: lead
• NHS Tayside: collaborator
• Insmed Incorporated: collaborator

Study Sites (16)

NHS Grampian

Aberdeen, United Kingdom

Location

Royal United Hospitals Bath NHS Foundation Trust

Bath, United Kingdom

Location

University Hospitals Birmingham NHS Foundation Trust

Birmingham, United Kingdom

Location

Cardiff & Vale University Health Board

Cardiff, United Kingdom

Location

NHS Tayside

Dundee, United Kingdom

Location

NHS Fife

Dunfermline, United Kingdom

Location

Frimley Health NHS Foundation Trust

Frimley, United Kingdom

Location

Princess Alexandra Hospital NHS Trust

Harlow, United Kingdom

Location

NHS Highland

Inverness, United Kingdom

Location

NHS Forth Valley

Larbert, United Kingdom

Location

University Hospitals of Leicester NHS Trust

Leicester, United Kingdom

Location

Liverpool University Hospitals NHS Foundation Trust

Liverpool, United Kingdom

Location

Portsmouth Hospitals NHS Trust

Portsmouth, United Kingdom

Location

Sheffield Teaching Hospitals NHS Foundation Trust

Sheffield, United Kingdom

Location

University Hospitals North Midlands NHS Trust

Stoke-on-Trent, United Kingdom

Location

NHS Lanarkshire

Wishaw, United Kingdom

Location

MeSH Terms

Conditions

COVID-19

Interventions

brensocatib

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Professor James D Chalmers
• Organization: University of Dundee, UK

jchalmers@dundee.ac.uk

01382660111

Study Officials

• James Chalmers

  University of Dundee

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Respiratory Research

Study Record Dates

• First Submitted: January 25, 2021
• First Posted: March 26, 2021
• Study Start: June 5, 2020
• Primary Completion: February 28, 2021
• Study Completion: February 28, 2021
• Last Updated: August 22, 2023
• Results First Posted: August 22, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

GB (16)