A 12 Month Proof of Concept Phase IIa Study of Nemiralisib (GSK2269557) in Symptomatic COPD Participants with a History of Exacerbations

Phase 1

Conditions: 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
Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Registration Number: EUCTR2017-004564-35-ES

Lead Sponsor: GlaxoSmithKline, S.A.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Not specified

Target Recruitment: 400

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. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participa

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 <30%) neurological, psychiatric, renal, hepatic, immunological, endocrine (including uncontrolled diabetes or thyroid disease), peptic ulcer disease, or hematological abnormalities. Significant is defined as anydisease that, in the opinion of the investigator, would put the safety of the subject at risk through participation, or which would affect the efficacy or safety analysis if the disease/condition exacerbated during the study. (Note: Participants with adequately treated and well controlled concurrent medical conditions (e.g. hypertension or noninsulin-dependent diabetes mellitus[NIDDM]) are permitted to be entered into the study).
7. Lung resection: Having undergone lung volume reduction surgery or lung resection for any other reason (e.g. lung carcinoma)
8. Liver disease
a. ALT >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
e. Positive hepatitis C antibody test result at Screening orwithin 3 months

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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