A phase 3 study of mepolizumab as an add-on treatment in COPD participants.
- Conditions
- Chronic Obstructive Pulmonary Disease (COPD)MedDRA version: 21.1Level: LLTClassification code 10010952Term: COPDSystem Organ Class: 100000004855Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
- Registration Number
- EUCTR2018-001540-56-PL
- Lead Sponsor
- GlaxoSmithKline Research & Development Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 1400
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 historical count of =150 cells/µL not older than 12 months not within 14 days of COPD exacerbation OR meeting threshold of =150 cells/µL at Screening Visit 1.
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 Visit 1 of:
• two or more moderate COPD exacerbations that were treated with systemic corticosteroids (intramuscular (IM), intravenous, or oral) and/or treatment with antibiotics.
• at least one severe COPD exacerbation requiring hospitalization
Note: At least one exacerbation must have occurred while participant was taking inhaled triple therapy.
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 Monitor.
7. Current or former cigarette smokers with a history of cigarette smoking of =10 pack-years at 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)]. Former smokers are defined as those who have stopped smoking for at least 6 months prior to Screening Visit 1.
Note: Pipe and/or cigar use cannot be used to calculate pack-year history.
8. Contraceptive use for women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
Female Participants:
A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least on
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 lowerrespiratory tract infection within the 4 weeks prior to Visit 1.
4.Participants with lung volume reduction surgery within the 12 months prior to Visit 1.
5.Participation in the acute phase of a pulmonary rehabilitation program within 4 weeks prior to 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).
Participants are excluded if an abnormal ECG finding from the 12-lead ECG conducted at 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.
8.Participants with any of the following would be excluded:
• Myocardial infarction or unstable angina in the 6 months prior to Visit 1
• Unstable or life threatening cardiac arrhythmia requiring intervention in the 3 months prior to 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 Polyangiitis (EGPA, also known as Churg-Strauss Syndrome), or Eosinophilic Esophagitis.
11.Participants with a known, pre-existing parasitic infestation within 6 months prior to Visit 1.
12.A current malignancy or previous history of cancer in remission for less than 12 months prior to Visit 1 (Participants that had localized carcinoma of the skin or cervix which was resected for cure will not be excluded).
Note: for South Korea: Korean participants with a diagnosis of malignancy within 5 years of Visit 1 are excluded.
13.A known immunodeficiency (e.g. human immunodeficiency virus – HIV), other than that explained by the use of corticosteroids taken for COPD.
14.Cirrhosis or current unstable liver disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, esophagea
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