| Eligibility |
Inclusion Criteria:
- Written informed consent must be obtained before any assessment is performed.
- Male or female patients aged =18 years at screening.
- Proven diagnosis of bronchiectasis by chest CT.
- Evidence of sputum bacterial load of =10^6 CFU/mL with at least one potentially
pathogenic microorganism at screening (H. Influenzae, M catarrhalis, S aureus, S
pneumoniae, Enterobacteriaceae, P aeruginosa, Stenotrophomonous maltophilia, or any
potential pathogenic non-fermenting Gram negative bacteria measured by
dilution/outgrowth).
- Documented history of at least one bronchiectasis exacerbation between January 2019 to
study screening.
- Patients with bronchial hypersecretion, defined as productive cough that occurs on
most days (defined as >50% days) for at least three consecutive months within 12
months prior to screening, as assessed by documentation of patient recollection
(anamnesis) or documented in patients' record.
- Patients are allowed to stay on fixed or free combinations of LABA/LAMA or LABA/ICS or
LABA/LAMA/ICS as maintenance therapy if they are treated with them at a stable dose
for the last 3 months prior to screening. Patients are also allowed to stay on
macrolides as maintenance therapy if they are treated with them at a stable dose 3
months before screening. If prescribed, patients are included in the study with
unchanged chest physiotherapy for at least 4 weeks prior to screening. Patients will
be allowed to use mucolytics or hyperosmolar agents if they were treated with them
before study start.
- Clinically stable pulmonary status in the opinion of the investigator and unlikely to
require any change in the standard regimen of care during the course of the study.
- Able to perform reliable, reproducible pulmonary function test maneuvers per American
Thoracic Society/European Respiratory Society (ATS/ERS) guidelines at screening. At
screening, patients who have failed to meet ATS/ERS requirements for acceptability and
reproducibility for spirometry will be allowed one additional repeat testing session
during the screening period.
Exclusion Criteria:
- Use of other investigational drugs at the time of enrollment, or within 5 half-lives
of enrollment, or within 30 days, whichever is longer; or longer if required by local
regulations. Current or planned participation to another clinical trial during this
study.
- History of hypersensitivity to the study drugs or to drugs of similar chemical classes
or excipients.
- Patients with a history of long-QT syndrome or the QTcF interval at Screening or
baseline is prolonged (QTcF >450 ms in males, >460 ms in females).
- Patients who have a clinically significant ECG abnormality before randomization Note:
Clinically significant abnormalities may include but are not limited to the following:
left bundle branch block, Wolff-Parkinson-White syndrome, clinically significant
arrhythmias (e.g. atrial fibrillation, ventricular tachycardia).
- Patients with a history or current treatment for hepatic disease including but not
limited to acute or chronic hepatitis, cirrhosis or hepatic failure. A history of
resolved Hepatitis A is not exclusionary. Patients with prothrombin time international
normalized ratio(PT/INR) of more than 1.5xULN at screening. Patients excluded for the
PT/INR of more than 1.5xULN can be re-screened when the values have returned to
normal.
- History of lung transplant or malignancy of any organ system (other than localized
basal cell carcinoma of the skin), treated or untreated, within the past 5 years,
regardless of whether there is evidence of local recurrence or metastases, with the
exception of localized basal cell carcinoma of the skin. Patients with segmentectomy
for other reasons than cancer are allowed to be included in the study. Patients with a
history of cancer and 5 years or more disease free survival time may be included in
the study by agreement with Novartis Medical Monitor on a case-by-case basis.
- Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a
female after conception and until the termination of gestation, confirmed by a
positive hCG laboratory blood test.
- Women of child-bearing potential, defined as all women physiologically capable of
becoming pregnant, unless they are using acceptable effective methods of contraception
during study participation.
- Use of prescription drugs prohibited as stated in the Section 6.2.2 within 1 week
prior to Day 1.
- Clinical significant laboratory values abnormalities (including G-GT, AST, ALT, total
bilirubin or creatinine) in the opinion of the investigator at screening. For
additional guidance on hepatic parameters refer to exclusion criterion #5.
- Patients requiring long-term oxygen therapy for chronic hypoxemia. This is typically
patients requiring oxygen therapy >12 h per day delivered by home oxygen cylinder or
concentrator. Note: Nocturnal oxygen therapy for transient oxygen desaturations during
sleep is allowed.
- Patients with bronchiectasis who have had a pulmonary exacerbation with a
deterioration in three or more of key symptoms for at least 48 h and a clinicians
determines that a change bronchiectasis treatment is required within 4 weeks prior to
screening.
- Hemoptysis, requiring medical intervention at any time within 4 weeks prior to
screening.
- Bronchiectasis predominantly characterized by isolated cavitary lung lesions.
- Patients with bronchiectasis requiring therapy that may interfere with the assessment
of QBW251 efficiency or that are unlikely to respond to QBW251
- Current or ex-smokers with severe emphysema.
- Patients with another concomitant pulmonary disease according to the definition of the
International ERS/ATS guidelines, including but not limited to COPD, asthma,
interstitial pulmonary fibrosis (IPF), sarcoidosis or other granulomatous or
infectious process. Concomitant COPD and asthma with characteristics of airway
hyperresponsiveness as well as COPD Asthma overlap syndrome are allowed as long as it
is not the main, primary diagnosis.
- Patients currently receiving treatment for nontuberculous mycobacterial (NTM)
pulmonary disease.
- Patients with a known history of non-compliance to medication or who are unable or
unwilling to complete an electronic patient diary or patient reported outcome
questionnaire.
- Recent (within three years of screening) and/or recurrent history of autonomic
dysfunction (e.g., recurrent episodes of fainting, palpitations, etc).
- Patients with a major vascular surgery in the 6 months prior to the screening visit.
- Patients who have clinically significant renal, cardiovascular (such as but not
limited to unstable ischemic heart disease, NYHA Class III/IV left ventricular
failure, myocardial infarction), neurological, endocrine, immunological, psychiatric,
gastrointestinal, or hematological abnormalities, which could interfere with the
assessment of the efficacy and safety of the study treatment, or patients with Type I
diabetes or uncontrolled Type II diabetes.
- Known or suspected history of ongoing, chronic or recurrent infectious disease of HIV,
Hepatitis B/C.
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