Global amendment 1 part 1 - The following main changes were introduced: 1) the “rate of pulmonary exacerbations up to 48 weeks”, which had been a secondary endpoint in the initial protocol, was defined as key secondary endpoint. Section 7 was partially re-structured to reflect this change. 2) In the initial protocol, Quality of Life Questionnaire – Bronchiectasis (QOL-B) was a further endpoint. It was changed to ‘QOL-B respiratory symptoms domain score’ as a secondary endpoint, and ‘QOL-B scores except respiratory symptoms domain score’ as further endpoint. 3) Second sampling time point was added for P. aeruginosa at End of treatment (EOT). 4) Updates to the flow chart were made for clarification. 5) Bone metabolism markers were removed from safety parameters and added as biomarkers. It was clarified that sampling was to take place fasting and at the same time of the day, if possible. Sampling frequency was increased and a new additional bone metabolism marker (Tartrate resistant acid phosphatase 5b -TRAP5B) was added. 6) Clarification that chronic treatment with concomitant strong Cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp) inhibitors and inducers was restricted. Examples for such medications were provided. 7) Safety monitoring committee was replaced by Data Monitoring Committee (DMC). No Sponsor-internal personnel was involved in interim analyses. 8) Changes were made in contraception requirements: a) footnote on definition of postmenopausal status: statement added that Follicle stimulating hormone (FSH) level could be used for confirmation in questionable cases; b) Contraception was extended from 30 days to 75 days after last drug intake for both Women of childbearing potential (WOCBP) and male participants with WOCBP partners. 9) For Korea, legal age of 19 was added and Korea was namely mentioned as a country where WOCBP were not allowed to participate.

Global amendment 1 part 2 - 10) Exclusion criterion #1 was changed to: Aspartate aminotransferase (AST) and / or Alanine aminotransferase (ALT) >3.0 x Upper limit of normal (ULN) at Visit 1, or moderate or severe liver disease (defined by Child-Pugh score B or C hepatic impairment). 11) Exclusion criterion #4: it was clarified that patients who may be at risk by participating in the trial were not to be included, and it was added that this judgement was to be made by the investigator based on laboratory and medical examinations. 12) Exclusion criterion #6: it was added that patients with allergic bronchopulmonary aspergillosis being treated or requiring treatment were to be excluded, and clarified that patients with fungal infection and not responsive to treatment should be excluded. 13) Exclusion criterion #7: it was clarified that patients with acute infections in the need of treatment were not to be randomised. 14) Exclusion criterion #17 was changed to: currently enrolled in another investigational device or drug trial, or less than 30 days or 5 half-lives, whichever was longer, prior to Visit 2 since ending another investigational device or drug trial(s). 15) New exclusion criterion #20: Contraindications to the class of drugs under study including known hypersensitivity to the drug or its excipients. 16) Additional discontinuation criterion: The investigator considered that treatment continuation was negatively impacting the well-being of the patient, and that treatment discontinuation was in the best interest of the patient.

Global amendment 3 - The following main changes were introduced: 1) addition of new data on embryofoetal developmental toxicology outcomes. 2) The Pharmacokinetic (PK) safety evaluation of brensocatib was referenced. 3) New data from the Phase I trial 1397-0003 were added. 4) The Leicester Cough Questionnaire (LCQ) and Cough and Sputum Assessment Questionnaire (CASA-Q) were removed, and the Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) was included. 5) A new section was added on Salbutamol/Albuterol as an Auxiliary medicinal product (AxMP). 6) Medications were added that needed to be stable prior to randomisation to reduce variability of bone turnover biomarkers. 7) A new major metabolite was added. 8) Information on Adverse events (AEs) was updated. 9) The wording regarding male and female contraception was revised. 10) Exclusion criteria: ‘acute Severe acute respiratory syndrome coronavirus (SARS CoV) 2 infection’ was deleted as an individual criterion and added into exclusion criterion #7 instead. 11) The contraception requirement after last trial drug intake was prolonged from 75 days to 9 months for WOCBP, and to 6 months for male participants with WOCBP partners. 12) It was added that for Hepatitis C virus (HCV) a Ribonucleic acid (RNA) test was to be performed if Hepatitis C antibodies result was positive, to confirm if the infection was active. Global amendment 3 includes the changes made in the global amendement 2, which was an internal version and never submitted to any Competent Authority (CA)/Institutional Review Board (IRB)/Independent Ethics Committee (IEC).

Global amendment 4 - The following main changes were introduced: 1) It was clarified that an interim pharmacodynamic analysis was not planned. 2) The implementation of an adjudication committee was introduced, and a further endpoint ‘rate of adjudicated pulmonary exacerbation’ was added. 3) Periodontal discontinuation criteria were corrected, and assessment procedures clarified. 4) The subgroups with history of pulmonary exacerbations at baseline were changed from ‘0-2, ≥ 3’ to ‘0-1, ≥ 2’. 5) Pre-dose PK time window for trough samples at Visits 3, 5 and 7 was extended from -1 h to -2 h.