A randomised double-blind placebo-controlled trial of Brensocatib (INS1007) in patients with severe COVID-19

Phase 1

• Conditions: COVID-19; MedDRA version: 23.0Level: PTClassification code 10051905Term: Coronavirus infectionSystem Organ Class: 10021881 - Infections and infestations; Therapeutic area: Diseases [C] - Virus Diseases [C02]

• Registration Number: EUCTR2020-001643-13-GB
• Lead Sponsor: niversity of Dundee

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-04-29
• Last Update Posted: 21 September 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

•Male or female
•=16 years of age
•SARS-CoV-2infection (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:
oRadiographic infiltrates by imaging (e.g. chest x-ray, computed tomography (CT) scan)
OR
oEvidence of rales/crackles on physical examination
OR
oPeripheral capillary oxygen saturation (SpO2) =94% on room air prior to randomization
OR
oRequiring supplemental oxygen.
OR
oLymphocyte 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
^Where a patient has been admitted to hospital for a non COVID-19 reason and develops COVID-19 symptoms whilst an in-patient, randomisation my occur up to 96 hours from onset of symptoms.

Are the trial subjects under 18? yes
Number of subjects for this age range: 20
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 100
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 180

Exclusion Criteria

•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. eGFR < 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 treatment with 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 CI.
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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified