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 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 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.

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 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 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.

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.

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.