Chronic obstructive pulmonary disease Respiratory Other chronic obstructive pulmonary disease
Conditions
Interventions
All participants will be centrally assigned to randomized study treatment using an IxRS system. Randomization will be stratified by smoking status (current/former) to obtain an approximately 1:1 ratio
Sponsors
Roche (Switzerland)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 14/06/2022: 1. Between 35 and 75 years of age (inclusive) 2. Participants with >=12-month diagnosis of COPD 3. Radiologic evidence of air trapping at screening based on chest HRCT conducted per imaging acquisition protocol and reviewed by the imaging central reader 4. Extent of emphysema on HRCT at screening is =30% and == 2 or >= 1 leading to hospitalization within the last 12 months 6. COPD assessment test (CAT) score >=10 and with a clinical diagnosis of chronic bronchitis, characterized by cough and sputum production on most days for a minimum of 3 months during the last year 7. Participant must have a body mass index (BMI) between 18 and 35 kg/m² 8. Abnormal laboratory values high sensitivity CRP (hs-CRP) >= 3 mg/L at screening and absolute neutrophil count >= 6.0 x 109/L in whole blood at screening 9. Vital signs (body temperature, systolic and diastolic blood pressure, pulse rate, and respiratory rate) will be assessed in the sitting position after the subject has rested for at least 3 minutes 10. Unchanged standard regimen of care for >= 4 weeks prior to screening 11. Ex-smokers with at least a 10-pack year smoking history or current smokers with at least a 10 pack-year smoking history who smoke ==12-month diagnosis of COPD 3. Radiologic evidence of air trapping at screening based on chest HRCT conducted per imaging acquisition protocol and reviewed by the imaging central reader 4. Extent of emphysema on HRCT at baseline is = 30% and == 2 or >= 1 leading to hospitalization within the last 12 months 6. COPD assessment test (CAT) score >=10 and with a clinical diagnosis of chronic bronchitis, characterized by cough and sputum production on most days for a minimum of 3 months during the last year 7. Participant must have a body mass index (BMI) between 18 and 35 kg/m² 8. Abnormal laboratory values 9. Vital signs (body temperature, systolic and diastolic blood pressure, pulse rate, and respiratory rate) will be assessed in the sitting position after the subject has rested for at least 3 minutes 10. Unchanged standard regimen of care for >= 4 weeks prior to screening 11. Ex-smokers with at least a 10-
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 14/06/2022: 1. Any condition or disease detected during the medical interview/physical examination that would render the patient unsuitable for the study, place the patient at undue risk, or interfere with the ability of the patient to complete the study 2. Known active or uncontrolled bacterial, viral, fungal, mycobacterial, or other infection, excluding fungal infection of nail beds, including participants exhibiting symptoms consistent with SARS-CoV-2 within 2 weeks prior to screening 3. Positive polymerase chain reaction (PCR) test for SARS-CoV-2 within 6 weeks prior to Day 1 4. Diagnosis of severe bronchiectasis in chart or history 5. Participants with another concomitant pulmonary disease, including but not exclusive of, interstitial pulmonary fibrosis, sarcoidosis, or other granulomatous or infectious process 6. Participants treated for active asthma within 2 years prior to the screening visit 7. Any COPD exacerbation or upper or lower respiratory tract infection requiring antibiotics, oral steroids, or hospitalization within 2 weeks prior to screening, during the screening period, or during the run-in period 8. Participants requiring long-term oxygen therapy for daytime hypoxemia 9. Participants with a diagnosis of alpha-1 antitrypsin deficiency 10. History of lung transplant or malignancy of any organ system (other than localized basal cell carcinoma of the skin) within the past 5 years 11. Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardize the subject in case of participation in the study 12. History of clinically significant ECG abnormalities, or ECG abnormalities at screening 13. Known family history or known presence of long QT syndrome 14. Participant with a history of acute coronary syndrome in 3 months prior to the screening visit 15. Participants with a history of coronary artery bypass surgery or other major vascular surgery within 6 months prior to the screening visit 16. Evidence of urinary obstruction or difficulty in voiding 17. History of any clinically significant hepatic disease or cirrhosis 18. Significant illness not resolved within 2 weeks prior to screening 19. Use of systemic steroids, ICS, theophylline, and phosphodiesterase 4 (PDE4) inhibitors within 4 weeks of screening 20. Vaccines within 4 weeks prior to the first dose 21. Current treatment with medications that are well known to prolong the QT interval 22. Donation or loss of 450 mL or more of blood within 8 weeks prior to initial dosing, or longer if required by local regulation 23. Plasma donation > 150 mL within 7 days prior to first dosing 24. 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 25. History of hypersensitivity to the study drugs or to drugs of similar chemical classes or excipients 26. QTcF > 450 ms in male participants and > 470 ms in female participants 27. Liver function test abnormalities at screening. Re-testing during the screening period is possible once. This laboratory assessment may be repeated once during the screening period, if necessary 28. Anemia (hemoglobin levels >10.0 g/dl at screening). This laboratory assessment may be repeated once during the screening period, if necessary 29. Clinical evidence of impaired renal function as indicated by clinically
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Incidence and severity of adverse events (AEs) and serious AEs (SAEs) determined according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v5.0) and causal relationship of AEs, incidence of SAEs and AEs leading to treatment discontinuation, recorded throughout the study up to 12 weeks 2. Incidence of abnormal laboratory findings 3. Incidence of abnormal vital signs and electrocardiogram (ECG) parameters Timepoint(s) for 1-3: up to 12 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Pre-bronchodilator (pre-BD) forced expiratory volume in 1 second (FEV1), measured by spirometry 2. Post-bronchodilator (post-BD) FEV1 measured by spirometry 3. Pre-BD FEV1 percentage of predicted measured by spirometry 4. Post-BD FEV1 percentage of predicted measured by spirometry 5. Pre-BD total lung capacity (TLC) measured by body plethysmography 6. Pre-BD residual volume (RV) measured by body plethysmography 7. Pre-BD functional residual capacity (FRC) measured by body plethysmography 8. RV/TLC ratio measured by body plethysmography 9. Pre-BD forced expiratory flow over the middle one half of the FVC (FEF25-75) measured by spirometry 10. Post-BD FEF25-75 measured by spirometry 11. Pharmacokinetic (PK) parameters of selnoflast in blood by PK population analysis Timepoints for 1-10: Screening (Day-42 to Day -15), Day -14, Day 1, Day 14, Day 28, Day 42, at unscheduled visit, at early termination visit Timepoints for 11: Day 1, Day 7, Day 14, Day 21, Day 28, at unscheduled visit | — |
Countries
Germany, Israel, Netherlands, Spain, United Kingdom, United States of America
Contacts
Public ContactClinical Trials
Outcome results
None listed