English Study evaluating safety and efficacy of mepolizumab in the treatment of COPD patients with frequent exacerbations.

Phase 1

• Conditions: Treatment of severe Chronic Obstructive Pulmonary Disease (COPD) in patients presenting frequent exacerbations; MedDRA version: 19.0Level: PTClassification code 10009033Term: Chronic obstructive pulmonary diseaseSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders; Therapeutic area: Diseases [C] - Immune System Diseases [C20]

• Registration Number: EUCTR2013-004297-98-DE
• Lead Sponsor: GlaxoSmithKline Research & Development Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-04-03
• Last Update Posted: 3 April 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 660

Inclusion Criteria

1.COPD diagnosis: Subjects with a clinically documented history of COPD for at least 1 year in accordance with the definition by the American Thoracic Society/European Respiratory Society

2.Severity of COPD: Subjects must present with the following:
- A measured pre and post-salbutamol FEV1/FVC ratio of <0.70 at Visit 1 to confirm the diagnosis of COPD
- A measured post-salbutamol FEV1> 20% and =80% of predicted normal values calculated using NHANES III reference equationsat Visit 1

3.History of exacerbations: A well documented history (e.g., medical record verification) in the 12 months prior to Visit 1 of:
-at least two moderate COPD exacerbations. Moderate is defined as the use of systemic corticosteroids (intramuscular (IM), intravenous, or oral) and/or treatment with antibiotics.
OR
- at least one severe COPD exacerbation. Severe is defined as having required hospitalization

4.Concomitant COPD therapy: A well documented requirement for optimized standard of care (SoC) background therapy that includes ICS plus 2 additional COPD medications (i.e., triple therapy) for the 12 months prior to Visit 1 and meets the following criteria:
Immediately prior to Visit 1, minimum of 3 months of use of an a) inhaled corticosteroid at a dose =500 mcg/day fluticasone propionate dose equivalent plus b) LABA and c) LAMA.
For subjects who are not continually maintained on ICS plus LABA plus LAMA for the entire 12 months prior to Visit 1 use of following is allowed (but not in the 3 months immediately prior to Visit 1):
a.inhaled corticosteroid at a dose =500 mcg/day fluticasone propionate dose equivalent plus
b.a LABA or a LAMA and
c.use of at least one other class of COPD medication suggested by the 2013 GOLD guidelines for patients who are prone to exacerbation (i.e., phosphodiesterase-4-inhibitors, methylxanthines, or a combination of short acting beta2-agonist and short acting muscarinic antagonist).

5.Informed Consent: Able to give written informed consent prior to participation in the study, which will include the ability to comply with the requirements and restrictions listed in the consent form. Subjects must be able to read, comprehend, and write at a level sufficient to complete study related materials.

6.Gender: Male or Eligible Female
To be eligible for entry into the study females of child bearing potential must commit to consistent and correct use of an acceptable method of birth control from the time of consent, for the duration of the trial, and for 4 months after last study drug administration. See Appendix 1 for a listing of acceptable methods of birth control.

7.Age: At least 40 years of age at Visit 1

8.Smoking status: Subject with confirmed COPD are eligible to participate independent of their smoking status and smoking history, i.e. current smokers, never smokers or ex-smokers can be enrolled into the study.

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 330
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 330

Exclusion Criteria

1.Asthma:
•Current and Former Smokers: Subjects with a current diagnosis of asthma (those with a prior history are eligible if they meet inclusion criteria for a current diagnosis of COPD)
•Never-Smokers: Subjects with any history of asthma

2.Other respiratory disorders: The investigator must judge that COPD is the primary diagnosis accounting for the clinical manifestations of the lung disease. Subjects with a1-antitrypsin deficiency as the underlying cause of COPD are excluded. Also, excluded are subjects with active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, primary pulmonary hypertension, interstitial lung diseases or other active pulmonary diseases. Subjects are also excluded if maintenance use of bi-level positive airway pressure is required for the treatment of respiratory disorder.

3.COPD stability: Subjects with pneumonia, exacerbation, lower respiratory infection within the 4 weeks prior to Visit 1.

4.Lung resection: Subjects with lung volume reduction surgery within the 12 months prior to Visit 1.

5.Pulmonary rehabilitation program: Participation in the acute phase of a pulmonary rehabilitation program within 4 weeks prior to Visit 1. Subjects who are in the maintenance phase of a pulmonary rehabilitation program are not excluded.

6.Oxygen: Subjects receiving treatment with oxygen more than 4.0L/min. While breathing supplemental oxygen, subjects should demonstrate an oxyhemoglobin saturation greater than or equal to 89%.

7.12-lead ECG finding: An abnormal and significant ECG finding from the 12-lead ECG conducted at Visit 1 if considered to be clinically significant by the Investigator. Specific ECG findings that preclude subject enrolment are found in Appendix 2. 12-lead ECGs will be over-read by a centralized independent cardiologist to assist in consistent evaluation of subject eligibility. Results from the 12-lead ECG over-read must be received prior to assessing eligibility at Visit 2.

8.Unstable or life threatening cardiac disease: Subjects with any of the following would be excluded:
•Myocardial infarction or unstable angina in the last 6 months
•Unstable or life threatening cardiac arrhythmia requiring intervention in the last 3 months
•New York Heart Association (NYHA) Class IV Heart failure

9.Other diseases/abnormalities: Subjects with (historical or) current evidence of clinically significant, neurological, psychiatric, renal, hepatic, immunological, endocrine or haematological abnormalities that are uncontrolled.

10.Eosinophilic disease: Subjects with other conditions that could lead to elevated eosinophils such as Hypereosinophilic syndromes including Eosinophilic Granulomatosis with Polyangiitis or Eosinophilic Esophagitis.

11.Parasitic infection: Subjects with a known, pre-existing parasitic infestation within 6 months prior to Visit 1 are also excluded.

12.Malignancy: A current malignancy or previous history of cancer in remission for less than 12 months prior to Visit 1.

13.Immunodeficiency: A known immunodeficiency (e.g human immunodeficiency virus – HIV), other than that explained by the use of corticosteroids taken for COPD.

14.Liver disease: Unstable liver disease, cirrhosis, and known bilary abnormalities (with the exception of Gilbert’s syndrome or asymptomatic gallstones). Chronic stable hepatitis B and C are acceptable if subject otherwise meets entry criteria

15.Monoclonal antibodies: Subjects who have received a

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the efficacy and safety of mepolizumab 100 mg and 300 mg subcutaneous (SC) given every 4 weeks compared to placebo on the frequency of moderate and severe exacerbations in COPD subjects at high risk of exacerbations despite the use of optimized standard of care background therapy.;Secondary Objective: To evaluate other efficacy assessments of mepolizumab 100 mg and 300 mg subcutaneous (SC) compared to placebo on changes in quality of life, health care utilization, and symptoms.;Primary end point(s): Frequency of moderate and severe exacerbations. <br><br><br>Moderate exacerbations are defined as COPD exacerbations that require either systemic corticosteroids (intramuscular (IM), intravenous, or oral) and/or antibiotics. <br><br>Severe exacerbations are defined as COPD exacerbations requiring hospitalization or result in death.<br>;Timepoint(s) of evaluation of this end point: Over the 52 week treatment period

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): •Time to first moderate/severe exacerbation<br>•Frequency of COPD exacerbations requiring emergency department (ED) visits and/or hospitalizations<br>•Change from baseline mean total St. George’s Respiratory Questionnaire-COPD (SGRQ-C) score<br>•Change from baseline COPD assessment test (CAT) score<br>;Timepoint(s) of evaluation of this end point: As specified in the endpoint.