Chronic Obstructive Pulmonary Disease MedDRA version: 20.0 Level: PT Classification code 10009033 Term: Chronic obstructive pulmonary disease System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Sponsors
GlaxoSmithKline, S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Participants are eligible to be included in the study only if all of the following criteria apply: Age: 1. 40 to 80 years of age, inclusive, at Screening (Visit 1). 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 a common, preventable and treatable disease that is characterized by persistent respiratory symptoms and airflow limitation that is due to airway and/or alveolar abnormalities usually caused by significant exposure to noxious particles or gases.” 3. 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) 4. Current Acute Exacerbation of COPD: Acute exacerbation of COPD requiring an escalation in therapy to include oral/systemic corticosteroid(s) (prednisone 40 mg/day or equivalent) for 5 days and antibiotic(s) for 7 days; the dose and/or duration of prednisone (40 mg/day or equivalent) and/or the antibiotic can be modified according to the Investigator’s/medically qualified designee’s judgement or according to local country/institution practice. Acute exacerbation to be confirmed by an experienced physician and to represent a recent worsening of at least two major and one minor symptoms, one major and two minor symptoms, or all 3 major symptoms. i. Major symptoms: a. Subjective increase in dyspnea b. Increase in sputum volume c. Change in sputum colour ii. Minor symptoms: a. Increased cough b. Increased wheeze c. Sore throat d. Colds (nasal discharge and/or nasal congestion) e. Fever (oral temperature >37.5°C) without other cause Weight: 5. Body Mass Index: Body weight >=45 kg and body mass index (BMI) within the range 16-35 kg/m2 (inclusive) Sex: 6. Male and female subjects 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 the 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 the protocol OR ii. A WOCBP who agrees to follow the contraceptive guidance in Appendix 5 of the protocol during the 12-Week Double-Blind Treatment Period and for at least 5 halflives (10 days) after the last of double-blind study treatment. Informed Consent 7. Capable of giving signed informed consent as described in Appendix 3 of the protocol, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Are the trial subjects under 18? no Number of subje
Exclusion criteria
Exclusion criteria: Participants are excluded from the study if any of the following criteria apply: Medical Conditions 1. Asthma: Current diagnosis of asthma, according to the Global Initiative for Asthma [GINA, 2017]. Participants with a prior history of asthma are eligible if they have a current diagnosis of COPD. 2. Acute respiratory acidosis/invasive mechanical ventilation: pH 48 hours since diagnosis. 4. Chest X-ray (or CT scan): A 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). 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). 5. Pneumonia: Clinically significant pneumonia, identified by chest X-ray (CT scan) at Screening 6. Other respiratory disorders: A diagnosis of a1-antitrypsin deficiency as the underlying cause of COPD, active tuberculosis, lung cancer, clinically overt bronchiectasis (Note: focal bronchiectasis is not exclusionary), sarcoidosis, 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. 7. Other diseases/abnormalities: A history or current evidence of clinically significant and unstable disease 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 antigen (HBsAg) at Screening or within 3 months prior to first dose of study treatment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To characterize the dose response of nemiralisib administered in addition to SoC compared with placebo and SoC in participants diagnosed with an acute moderate or severe exacerbation of COPD; Secondary Objective: - To characterize the dose response and efficacy of nemiralisib administered in addition to SoC compared with placebo and SoC in participants diagnosed with an acute moderate or severe exacerbation of COPD. - To evaluate the treatment effect of nemiralisib in addition to SoC compared with placebo and SoC on symptoms indicative of an exacerbation and on health status using Patient-Reported Outcomes (PROs) in participants diagnosed with an acute moderate or severe exacerbation of COPD. - To evaluate the usage of rescue medication in patients diagnosed with an acute moderate or severe exacerbation of COPD. - To evaluate the population pharmacokinetics of nemiralisib in participants diagnosed with an acute moderate or severe exacerbation of COPD. - To assess the safety and tolerability of nemiralisib and placebo in participants diagnosed with an acute moderate or severe exacerbation of COPD. ; Primary end point(s): - Change from baseline in Clinic Visit trough forced expiratory volume in one second (FEV1) at Day 84 measured postbronchodilator. - Baseline is defined as the postbronchodilator FEV1 measured prior to the first dose of double-blind study treatment and post-bronchodilator on Day 1. ;Timepoint(s) of evaluation of this end point: Baseline and Day 84 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Rate of moderate and severe exacerbations over the 12-Week Treatment Period - Time to next moderate/severe exacerbation following index exacerbation - Change from baseline in Clinic Visit trough FEV1 measured pre and post-bronchodilator at Days 14, 28, 56, and 84 (Day 84: postbronchodilator is the primary endpoint; prebronchodilator is a secondary endpoint) and at hospital discharge (only for participants who are hospitalized for the index exacerbation) - Change from hospital discharge in clinic visit trough FEV1 measured pre- and postbronchodilator at Days, 14, 28, 56, and 84 (in participants hospitalized for index exacerbation only) EXAcerbations of Chronic Pulmonary Disease Tool (EXACT-PRO) - Proportion of participants achieving the EXACT definition of recovery from the index exacerbation by Days 14, 28, 56, and 84 - Time to recovery from index exacerbation - Severity of subsequent HCRU-defined exacerbation(s) defined by EXACT COPD Assessment Test (CAT) - Proportion of responders using the CAT at Treatment Days 28, 56, and 84, and following EXACT defined recovery from the index exacerbation - Change from baseline (Day 1) in CAT total score at Days 28, 56, and 84 and following EXACT defined recovery from the index exacerbation St. George’s Respiratory Questionnaire (SGRQ) Total Score - Proportion of responders on the St. SGRQ total score as measured by the SGRQ for COPD Patients (SGRQ-C) at Days 28, 56, and 84 - Change from baseline (Day 1) in SGRQ total score at Days 28, 56, and 84 - Rescue medication use (occasions/day), averaged over each week of treatment and over the 84-day treatment period - The percentage of rescue-free days (24- hour periods) during each week of treatment and over the 84-day tr | — |
Countries
Argentina, Australia, Canada, France, Germany, Italy, Korea, Republic of, Mexico, Netherlands, Poland, Romania, Russian Federation, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactCentro de Información
GlaxoSmithKline
Outcome results
None listed