Chronic obstructive pulmonary disease MedDRA version: 21.1 Level: LLT Classification code 10029972 Term: Obstructive airways disease (chronic) System Organ Class: 100000004855
Conditions
Sponsors
Novartis Pharma AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Patients who have signed an Informed Consent Form prior to initiation of any study-related procedure. •Male and female adults aged =40 years at screening. •Patients with stable COPD, stages GOLD 2-3, according to the current GOLD strategy (GOLD 2019) at screening. •Patients with a post-bronchodilator FEV1/FVC 0 CFU) for at least one strain of potentially pathogenic microorganism at screening (H influenzae, H parainfluenzae, P aeruginosa, S pneumoniae, S aureus, Moraxella catarrhalis, Enterobacteriaceae, Stenotrophomonas maltophilia, Burkholderia species, and Achromobacter species or any potential pathogenic bacteria measured by dilution/outgrowth. Any organism that is to be included and that is not included in the list of the protocol defined pathogens will be discussed case by case). Sputum samples may be re-collected and re-tested once during the screening period. •Patients who have been treated with a combination of LABA/LAMA or LABA/ICS or LABA/LAMA/ICS at a stable dose for the last 3 months prior to screening. COPD patients are allowed to stay on macrolides as background therapy if they have bronchiectasis as a secondary diagnosis and if they are treated with them at a stable dose 3 months before screening. •Patients with plasma fibrinogen level =320 mg/dL at screening. Fibrinogen may be re-tested once during the screening period. •A COPD Assessment Test (CAT) score of at least 10 at screening. •Current or ex-smokers who have a smoking history of at least 10 pack years at screening. (e.g. 10 pack years = 1 pack/day x 10 years, or 0.5 pack/day x 20 years) at screening. •Patients featuring chronic bronchitis, defined as productive cough that occurs on most days (defined as >50% of days) during at least 3 consecutive months in the year prior to screening, as assessed by documentation of patient recollection(anamnesis) or documented in patients' records. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 50 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: •Patients with a history of long-QT syndrome or whose QTcF interval at screening (Fridericia method) is prolonged (QTcF >450 ms in males, >460 ms in females). •Patients who have a clinically significant ECG abnormality before randomization. •Clinical laboratory values abnormalities (including Gamma GT, AST, ALT, total bilirubin or creatinine) considered as clinically significant in the opinion of the Investigator at screening. •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 uncontrolled Type II diabetes. •Patients with a history or current treatment for hepatic disease including but not limited to acute hepatitis, cirrhosis or hepatic failure. -Patients with stable chronic hepatitis may be included in the study by agreement with Novartis Medical Expert on a case-by-case basis. -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. •Patients with a history of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin. 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 Expert on a case-by-case basis. •Patients who develop a COPD exacerbation that required treatment with antibiotics and/or oral corticosteroids and/or hospitalization during screening. Re-screening is permitted after a minimum of 2 weeks after the resolution of the COPD exacerbation (i.e. 2 weeks after the stop of SOC therapy for exacerbation). •Patients who have had a respiratory tract infection within 4 weeks prior to screening. If a respiratory tract infection occurs during screening, patients can be re-screened after a minimum of 2 weeks after resolution of the respiratory tract infection. •Patients with history of asthma or any other clinically relevant lung diseases. •Patients with suspected active pulmonary tuberculosis or currently being treatment for active pulmonary tuberculosis. Note: Patients with a history of pulmonary tuberculosis can be enrolled if they meet the following requirements: history of appropriate drug treatment followed by negative imaging results within 12 months prior to screening suggesting low probability of recurrent active tuberculosis. •Patients with pulmonary lobectomy, lung volume reduction surgery, bronchoscopic lung volume reductions, or lung transplantation. •Patients participating in or planning to participate in the active phase of a supervised pulmonary rehabilitation program during the trial. Participation in a maintenance program is permitted. Note: the supervised pulmonary rehabilitation program as a maintenance program has to be ongoing for at least 3 months at the time of enrollment. •Patients with a body mass index (BMI) of more than 40 kg/m2. •Pregnant or nursing (lactating) women where pregnancy was defined as the
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the effect of QBW251 compared to placebo after 12 weeks of treatment on fibrinogen plasma concentration.;Secondary Objective: •To assess the effect of QBW251 compared to placebo after 12 weeks of treatment on: a)sputum bacterial load b)airway structure and function c)COPD subjects patients symptom burden changes d)health status e)changes in health-related quality of life f)COPD exacerbations g)clinical symptoms, cough and sputum h)pharmacokinetics i)spirometry •To assess the safety and tolerability of QBW251 in subjects with COPD;Primary end point(s): Change from baseline in fibrinogen plasma concentration.;Timepoint(s) of evaluation of this end point: 12 weeks of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Change from baseline in total bacteria load of colony forming units (CFU/mL) of potentially pathogenic microorganisms in sputum. •Change from baseline in airway wall and lumen parameters along with extent of global and regional air trapping, as measured by HRCT. •Change from baseline in COPD Assessment Test (CAT) questionnaire. •Changes from baseline in the Euro Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) questionnaire. •Change from baseline in St. George's Respiratory Questionnaire (SGRQ) total and domain scores. •Time to first COPD exacerbation, Proportion of subjects with exacerbations and Annualized rate of exacerbations as defined by EXACT-PRO questionnaire. •Change from baseline in Cough and Sputum Assessment Questionnaire (CASA-Q) domain scores. •Assessment of safety and tolerability (ECG intervals, vital signs, standard clinical laboratory Evaluations, adverse Events) •Assessment of drug exposure (Ctrough collected at pre-dose and Cmax at post-dose +3hr) on Day 1, Day 28, Day 56 and Day 84. Cmax and AUC post-dose (+1hr, +2hr, +3hr, +4hr, +6hr, +8hr) on Day 1 and Day 28 in a subset of subject population •Change from baseline in trough FEV1, FVC, and FEV1/FVC.;Timepoint(s) of evaluation of this end point: 12 weeks of treatment | — |
Countries
Austria, Germany, Switzerland, United Kingdom
Contacts
Public ContactMedizinischer Infoservice (MCC)
Novartis Pharma GmbH
Outcome results
None listed