Efficacy and Safety of Mepolizumab as an Add-on Treatment in Chronic Obstructive Pulmonary Disease (COPD)

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02105961
• Date of registration: 03/04/2014
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline
• Public title: Efficacy and Safety of Mepolizumab as an Add-on Treatment in Chronic Obstructive Pulmonary Disease (COPD)
• Scientific title: Study MEA117113: Mepolizumab vs. Placebo as Add-on Treatment for Frequently Exacerbating COPD Patients Characterized by Eosinophil Level
• Date of first enrolment: April 24, 2014
• Target sample size: 674
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02105961
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Investigator, Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

Argentina, Australia, Canada, Chile, Denmark, Germany, Japan, Korea, Republic of, Netherlands, Romania, Slovakia, Taiwan, Ukraine, United Kingdom, United States

Contacts

• Name: GSK Clinical Trials
• Affiliation: GlaxoSmithKline

Key inclusion & exclusion criteria

Inclusion Criteria:

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

- Severity of COPD: Subjects must present with the following: a measured pre and
post-salbutamol Forced expiratory volume in one second/ Forced vital capacity
(FEV1/FVC) ratio of <0.70 at Visit 1 to confirm the diagnosis of COPD; a measured
post-salbutamol FEV1> 20 percent and <=80 percent of predicted normal values
calculated using National Health and Nutrition Examination Survey (NHANES) III
reference equations at Visit 1

- 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. Note: At least one exacerbation must have occurred while the subject
was taking Inhaled corticosteroid (ICS) plus long acting beta2-agonist (LABA) plus
long acting muscarinic antagonist (LAMA). Prior use of antibiotics alone does not
qualify as a moderate exacerbation unless the use was specifically for the treatment
of worsening symptoms of COPD.

- Concomitant COPD therapy: A well documented requirement for optimized standard of care
background therapy that includes Inhaled corticosteroid (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;
Inhaled corticosteroid at a dose >= 500 micrograms (mcg)/day fluticasone propionate
dose equivalent plus; LABA and 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); inhaled corticosteroid at a dose >=500 mcg/day fluticasone propionate
dose equivalent plus; a LABA or a LAMA and; use of at least one other class of COPD
medication (i.e., phosphodiesterase-4-inhibitors, methylxanthines, or a combination of
short acting beta2-agonist and short acting muscarinic antagonist).

- 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.

- 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.

- Age: At least 40 years of age at Visit 1

- 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. Current smokers are defined as those with a
history of cigarette smoking of >=10 pack-years [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)]. Former smokers are defined as those
who meet the definition of a current smoker but have stopped smoking for at least 6
months prior to Visit 1. Never smokers are those that do not meet the definition of a
current or former smoker.

- French subjects: In France, a subject will be eligible for inclusion in this study
only if either affiliated to or a beneficiary of a social security category.

Exclusion Criteria:

- Subjects with 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.

- Other respiratory disorders: The investigator must judge that COPD is the primary
diagnosis accounting for the clinical manifestations of the lung disease. Subjects
with alpha1-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.

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

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

- 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.

- Oxygen: Subjects receiving treatment with oxygen more than 4.0 liters/minute (L/min).
While breathing supplemental oxygen, subjects should demonstrate an oxyhemoglobin
saturation greater than or equal to 89 percent.

- 12-lead Electrocardiography (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. 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.

- 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

- Other diseases/abnormalities: Subjects with (historical or) current evidence of
clinically significant, neurological, psychiatric, renal, hepatic, immunological,
endocrine (including uncontrolled diabetes or thyroid disease) or haematological
abnormalities that are uncontrolled. Significant is defined a


Age minimum: 40 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Pulmonary Disease, Chronic Obstructive

Intervention(s)

Drug: Mepolizumab

Drug: Placebo

Primary Outcome(s)

Rate of Moderate or Severe Exacerbations [Time Frame: From randomization to Week 52]

Secondary Outcome(s)

Change From Baseline in Mean COPD Assessment Test (CAT) Score [Time Frame: Baseline and Week 52]

Rate of COPD Exacerbations Requiring Emergency Department (ED) Visits and/or Hospitalizations (Hosp) [Time Frame: From randomization to Week 52]

Change From Baseline in Mean Total St. George's Respiratory Questionnaire (SGRQ) Score [Time Frame: Baseline and Week 52]

Time to First Moderate/Severe Exacerbation [Time Frame: From randomization to Week 52]

Secondary ID(s)

117113

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 06/04/2018
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02105961