A multi-center, randomized, double-blind, parallel-group, placebo controlled study of mepolizumab 100 mg SC as add-on treatment in participants with COPD experiencing frequent exacerbations and characterized by eosinophil levels (Study 208657)

Phase 3

Completed

Conditions: 10006436
Chronic inflammation in the airways and the lungs
COPD

Registration Number: NL-OMON54648

Lead Sponsor: GlaxoSmithKline

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 16

Inclusion Criteria

1.Participant must be at least 40 years of age at Screening Visit 1.
2. A peripheral blood eosinophil count of >=300 cells/µL from the hematology
sample collected at Screening Visit 0.
AND
A documented historical blood eosinophil count of >=150/µL in the 12 months
prior to Screening Visit 0 that meets the following: It must have been measured
between 12 months and 1 month prior to Visit 0, and it must not have been
measured within 14 days of a COPD exacerbation.
Participants with no documented historical blood eosinophil count of >=150
cells/µL must meet this threshold at the Screening Visit 1 assessment in order
to return for Randomization Visit 2.
3.Participants 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.
4.Participants must present with the following:
• A measured pre- and post-salbutamol FEV1/FVC ratio of <0.70 at Screening
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 equations at Screening Visit 1.
5. Participants must have a well-documented history (e.g., medical record
verification) in the 12 months prior to Screening Visit 1 of:
• Two or more moderate COPD exacerbations that were treated with systemic
corticosteroids (intramuscular (IM), intravenous, or oral) with or without
antibiotics.
OR
• At least one severe COPD exacerbation requiring hospitalization
Note: At least one exacerbation must have occurred while the participant was
taking inhaled triple therapy, ICS plus LABA plus LAMA unless documented
intolerance or safety risk with either of the two long-acting bronchodilators.
If intolerance is documented, ICS plus LABA or ICS plus LAMA would be allowable
after discussion with the Medical Monitor.
Note: COPD exacerbations related to COVID-19 infection must not be counted as
COPD exacerbations for inclusion in the study.
6. Participants must have a well-documented requirement for optimized standard
of care background therapy that includes ICS plus 2 additional COPD medications
(i.e., ICS-based triple therapy) for the 12 months prior to Screening Visit 1
and meets the following criteria:
• Immediately prior to Screening 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 unless documentation of safety or
intolerance issues related to LABA or LAMA.
• For participants who are not continually maintained on ICS plus LABA plus
LAMA for the entire 12 months prior to Visit 1 use of the 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.inhaled LABA or inhaled LAMA and
c.Phosphodiesterase-4-inhibitors, methylxanthines, or scheduled daily use of
short acting beta2-agonist (SABA) and/or short acting muscarinic
antagonist (SAMA).
Note: Where intolerance or safety risk is documented for either LAMA or LABA,
ICS-based inhaled dual maintenance therapy, either ICS plus LABA or ICS plus
LAMA, is allowed in the 12 months prior to Visit 1 and during the clinical
trial but must be discussed with the Medical Mo

Exclusion Criteria

1. Participants with a past history or concurrent diagnosis of asthma are
excluded regardless of whether they have active or inactive disease.
2. The Investigator must judge that COPD is the primarydiagnosis accounting for
the clinical manifestations of the lung disease. Participantswith a1-
antitrypsin deficiency as the underlying cause of COPD are excluded.
Also,excluded are participants with active tuberculosis, lung cancer,
bronchiectasis, sarcoidosis, lung fibrosis, primary pulmonary hypertension,
interstitial lung diseases
or other active pulmonary diseases.
3. Participants with pneumonia, COPD exacerbation, or lower respiratory tract
infection within the 4 weeks prior to Screening Visit 1.
4. Participants with lung volume reduction surgery within the 12 months prior
to Screening Visit 1.
5. Participation in the acute phase of a pulmonary rehabilitation program
within 4 weeks prior to Screening Visit 1. Participants who are in the
maintenance phase of a pulmonary rehabilitation program are not excluded.
6. Participants receiving treatment with oxygen more than 2 L/min at rest over
24 hrs. For participants receiving oxygen treatment, participants should
demonstrate an oxyhemoglobin saturation greater than or equal to 89% while
breathing supplemental oxygen.
7. Participants with a QT interval, from the ECG conducted at Screening Visit
1, corrected with Fridericia's formula (QTcF) >450 msec (or QTcF >480 msec in
participants with bundle branch block).
QTcF is the QT interval corrected for heart rate according to Fridericia*s
formula that is selected for this study. It is either machine-read or manually
over-read. when not automatically machine read. This specific formula must be
used to determine eligibility and discontinuation for an individual participant.
Participants are excluded if an abnormal ECG finding from the 12-lead ECG
conducted at Screening Visit 1 is considered to be clinically significant and
would impact the participant's participation during the study, based on the
evaluation of the Investigator.
Note: Where a single ECG demonstrates a prolonged QTcF interval, obtain two
more ECGs readings at a minimum of 2 min apart over a brief recording period
(e.g., 5-10 min), The average of the triplicate QTcF measurements should be
used to determine eligibility.
8. Participants with any of the following would be excluded:
• Myocardial infarction or unstable angina in the 6 months prior to Screening
Visit 1
• Unstable or life threatening cardiac arrhythmia requiring intervention in the
3 months prior to Screening Visit 1
• New York Heart Association (NYHA) Class IV Heart failure
9. Participants with (historical or) current evidence of clinically
significant, neurological, psychiatric, renal, hepatic, immunological,
endocrine (including uncontrolled diabetes or thyroid disease) or hematological
abnormalities that are uncontrolled. Significant is defined as any disease
that, in the
opinion of the Investigator, would put the safety of the participant at risk
through participation, or which could affect the efficacy or safety analysis if
the disease/condition exacerbated during the study.
10. Participants with other conditions that could lead to elevated eosinophils
such as Hypereosinophilic syndromes including Eosinophilic Granulomatosis with
P

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary objective:<br /><br>To evaluate the efficacy of mepolizumab 100 mg subcutaneous (SC) compared to<br /><br>placebo, given every 4 weeks in liquid formulation by safety syringe (SS) to<br /><br>COPD participants at high risk of exacerbations despite the use of optimized<br /><br>COPD maintenance therapy.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary objective:<br /><br>To evaluate mepolizumab 100 mg SC compared to placebo given every 4 weeks in<br /><br>liquid formulation by SS on additional efficacy assessments, health related<br /><br>quality of life (HRQoL), health care utilization, and symptoms</p><br>