Phase 3
Completed N=406
STOP-COVID19: Superiority Trial Of Protease Inhibition in COVID-19
Source: ClinicalTrials.gov NCT04817332 ↗Enrolled (actual)
406
Serious AEs
18.5%
Results posted
Aug 2023
Primary outcomePrimary: Comparison of Participant Clinical Status Between Treatment Arms — 28; 40; 112; 129 participants — p=0.008
◆ Published Evidence
No publication linked
No peer-reviewed publication reporting this trial's results has been linked yet. This can indicate results are unpublished — a known publication-bias signal. We re-check periodically.
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Comparison of Participant Clinical Status Between Treatment Arms |
28; 40; 112; 129; 7; 11 | 0.008 sig |
| SECONDARY Improvement of One Category From Admission Using 7-point Ordinal Scale. |
159; 186 | 0.058 |
| SECONDARY Participant Clinical Status on 7-point Ordinal Scale |
22; 26; 103; 124; 12; 19 | — |
| SECONDARY Mean Change in the 7-point Ordinal Scale |
1.0; 1.3; 1.0; 1.2; 0.9; 1.1 | — |
| SECONDARY 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. |
172; 195 | — |
| SECONDARY Change From Baseline of National Early Warning Score (NEWS). |
1; 0; 2; 0; 0; 1 | — |
| SECONDARY Number of Oxygen Therapy Free Days |
24; 24.5 | — |
| SECONDARY Incidence and Duration of New Oxygen Therapy Use During the Trial |
0; 0 | — |
| SECONDARY Number of Mechanical Ventilator Free Days |
28; 28 | — |
| SECONDARY Incidence and Duration of New Mechanical Ventilation Use During the Trial. |
0; 0 | — |
| SECONDARY Duration of Hospitalisation (Days). |
8.4; 8.2 | — |
| SECONDARY 28-day Mortality |
29; 23 | — |
| SECONDARY Cumulative Incidence of Serious Adverse Events (SAEs) |
40; 35 | — |
| SECONDARY Discontinuation or Temporary Suspension of Treatment |
13; 12 | — |
| SECONDARY Changes in White Cell Count (x10^9/L) Over Time (Hospitalised Participants Only) |
8.9; 8.5 | — |
| SECONDARY Changes in Haemoglobin (g/L) Over Time (Hospitalised Participants Only) |
195.4; 105.5 | — |
| SECONDARY Changes in Platelets (x10^9/L) Over Time (Hospitalised Participants Only) |
270; 269 | — |
| SECONDARY Changes in Creatinine (Umol/L) Over Time (Hospitalised Participants Only) |
84.9; 84.1 | — |
| SECONDARY Changes in Total Bilirubin (Umol/L) Over Time (Hospitalised Participants Only) |
8.4; 9.3 | — |
| SECONDARY Changes in Alanine Aminotransferase (U/L) Over Time (Hospitalised Participants Only) |
62.8; 52.3 | — |
| SECONDARY Changes in Aspartate Aminotransferase U/L Over Time (Hospitalised Participants Only) |
22; 28.8 | — |
| SECONDARY Adverse Events of Special Interest- Hyperkeratosis, Infections and Dental Complications |
0; 0; 0; 1; 6; 7 | — |
Eligibility Criteria
Inclusion Criteria
6.1. Inclusion criteria
- 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 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.
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Data sourced from ClinicalTrials.gov (NCT04817332). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.