Chronic Obstructive Pulmonary Disease (COPD)/chronic bronchitis and emphysema MedDRA version: 20.0 Level: LLT Classification code 10010953 Term: COPD exacerbation System Organ Class: 100000004855
Conditions
Sponsors
GlaxoSmithKline Research and Development Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Participants are eligible to be included in the study only if all the following criteria apply: Age 1. =40 and = 80 years of age inclusive, at the time of signing the informed consent. Type of Participant and Disease Characteristics 2. Diagnosis: An established clinical history of COPD in accordance with the definition by the American Thoracic Society/European Respiratory Society [GOLD, 2017] as follows: “Chronic obstructive pulmonary disease is common, preventable, and treatable disease that is characterized by persistent respiratory symptoms and airflowlimitation that is due to airway and/or alveolar abnormalities usually caused by significant exposure to noxious particles or gases.” 3. Documented history of COPD exacerbation (s): = 2 moderate exacerbations (prescription for antibiotics and/or oral corticosteroids) or = 1 severe exacerbation (hospitalisation or visit to the emergency room) in the 12 months prior to study participation Screening (Visit 1) 4. Smoking History: Current or former cigarette smoker with a history of cigarette smoking of = 10 pack-years. Former smokers are defined as those who have stopped smoking for at least 6 months prior to Screening (Visit 1). Number of pack years = (number of cigarettes per day/20) x number of years smoked) (e.g. 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years both equal 10 pack-years 5. Symptomatic COPD: A score of = 10 on the COPD Assessment Test (CAT) at Screening (Visit 1). Existing prescribed inhaled COPD maintenance therapy: Must be receiving a stable daily inhaled COPD maintenance therapy for their COPD for at least 3 months prior to Screening (Visit 1). Participants may continue their prescribed inhaled maintenance COPD therapy throughout the study (Run-in and Treatment Periods). Note: Participants receiving only PRN COPD medications are not eligible. 6. Must have a post-bronchodilator (albuterol/salbutamol) FEV1/ (forced vital capacity) (FVC) ratio = 0.70 and post-bronchodilator FEV1 = 80% of predicted [Quanjer, 2012] documented in the last 5 years. 7. Must not be taking antibiotics and/or oral corticosteroids for a COPD exacerbation within 6 weeks prior to Screening (Visit 1). 8. Able to perform lung function tests reliably.9. Must have the ability to use an electronic diary on a daily basis. Weight 10. Body weight = 45 kg and body mass index (BMI) within the range of 16-35 kg/m2 (inclusive). Sex 11. Male and female participants are eligible to participate in the study: a. Female participants: A female participant is eligible to participate if she is not pregnant (see Appendix 5 of protocol), not breastfeeding, and at least one of the following conditions applies: (i) Not a woman of childbearing potential (WOCBP) as defined in Appendix 5 of protocol OR (ii) A WOCBP who agrees to follow the contraceptive guidance inAppendix 5 of protocol during the 12-Month Double-Blind Treatment Period and for at least 5 half- lives (10 days) after the last dose of double-blind study treatment. C
Exclusion criteria
Exclusion criteria: Participants are excluded from the study if any of the following criteria apply: Medical Conditions 1. Current diagnosis of asthma, according to the Global Initiative for Asthma [GINA, 2017]. 2. Less than 6 weeks elapsed from completion of a course of antibiotics or oral corticosteroids for a recent COPD exacerbation. 3. Chest X-ray (or CT scan) that reveals evidence of clinically significant abnormalities not believed to be due to the presence of COPD. A chest X-ray (or CT scan) must be taken at Screening (Visit 1) (or historic radiograph or CT scan obtained within 3 months prior to screening). For sites in Germany: if a chest X-ray (or CT scan) within 1 year of Screening (Visit 1) is not available, approval to conduct a diagnostic chest X-ray (CT scan) will need to be obtained from the Federal Office for Radiation Protection (BfS). 4. Diagnosis of Pneumonia (chest X-ray or CT confirmed) within the last 3 months prior to Screening (Visit 1). 5. Other respiratory disorders: A diagnosis of a1-antitrypsin deficiency as the underlying cause of COPD, active tuberculosis, lung cancer, bronchiectasis (Note: focal bronchiectasis is not exclusionary), sarcoidosis, active tuberculosis, lung cancer, clinically overt bronchiectasis (Note: focal bronchiectasis is not exclusionary), pulmonary fibrosis (Note: focal fibrotic pulmonary lesions are not exclusionary), primary pulmonary hypertension, interstitial lung diseases, or any other respiratory condition that might, in the opinion of the investigator, compromise the safety of the subject or affect the interpretation of the results. 6. Other diseases/abnormalities: A history or current evidence of clinically significant and unstabledisease such as cardiovascular (e.g., patients requiring implanted cardioverter defibrillator [ICD], pacemaker requiring a rate set>60bpm, uncontrolled hypertension, New Your Heart Association Class IV [NYHA, 1994], known left ventricular ejection fraction 2xULN b. Total Bilirubin > 1.5xULN i. Isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35% c. Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert’s syndrome or asymptomatic gallstones d. Presence of hepatitis B surface a
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the clinical efficacy of nemiralisib compared with placebo to reduce the annual rate of moderate and severe exacerbations in participants with COPD. ; Secondary Objective: -To evaluate the effect of nemiralisib compared to placebo on further efficacy parameters pertaining to exacerbations and aligned with the primary objective -To evaluate the effect of nemiralisib compared with placebo on respiratory symptoms and Health related quality of life (HRQoL) using Patient Reported Outcomes (PROs) -To evaluate the effect of nemiralisib compared to placebo on lung function - To evaluate the effect of nemiralisib compared to placebo on rescue medication use -To evaluate the population pharmacokinetics of nemiralisib -To evaluate the safety and tolerability of nemiralisib compared with placebo ;Primary end point(s): Annualised rate of on-treatment moderate and severe exacerbations as defined by Health Care Resources Utilization (HCRU);Timepoint(s) of evaluation of this end point: Evaluated at 8 clinic visits over a 52-week treatment period | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Annualised rate of on-treatment HCRU/EXACT defined mile, moderate, and severe exacerbations Time to first on treatment HCRU/EXACT defined moderate/severe exacerbation Time to first on treatment HCRU/EXACT defined mild/moderate/severe exacerbation Evaluating Respiratory Symptoms (E-RS) in COPD (E-RS: COPD) Change from baseline in monthly weighted mean of E-RS: COPD (Total score and sub domains) - Proportion of responders according to ERS: COPD (Total score and sub domains) COPD Assessment Test (CAT) - Proportion of responders according to CAT at Weeks 4, 12, 28, 52 - Change from baseline in CAT total score at Weeks 4, 12, 28, 52 St. George’s Respiratory Questionnaire total score (measuring using SGRQ for COPD Patients (SGRQ-C)) - Proportion of responders SGRQ-C total score at Weeks 4, 12, 28, 52 - Change from baseline SGRQ-C total score at Weeks 4, 12, 28, 52 Exacerbations of Chronic Pulmonary Disease Tool (EXACT) - Annualised rate of HCRU/EXACT events - Time to first HCRU/EXACT event - Severity and duration of each HCRU/EXACT event - Change from baseline in clinic visit trough pre-and post-bronchodilator Inspiratory Capacity (IC), FEV1, and FVC, at Weeks, 4, 12, 28, 52 Rescue Medication Use (occasions/day) - The percentage of rescue-free days (24- hour periods) during each month of treatment and over the 12 Month Treatment Period PK concentrations and parameters - Incidence of Adverse Events (AEs; including serious AEs and AE of Special Interest (AESI)) - Vital Signs (pulse rate, systolic and diastolic blood pressure) measured at each | — |
Countries
Argentina, Germany, Mexico, Netherlands, Poland, Spain, Sweden, United States
Contacts
Public ContactClinical Trials Helpdesk
GlaxoSmithKline Research & Development Ltd
Outcome results
None listed