A clinical trial to investigate the effect of mepolizumab on severe COPD patients who are suffering from frequent exacerbations (or COPD attacks) and raised blood eosinophils

Phase 3

Active, not recruiting

Conditions: Chronic obstructive pulmonary disease with (acute) exacerbation,

Registration Number: CTRI/2022/12/047957

Lead Sponsor: GlaxoSmithKline Research & Development Limited

Brief Summary: This is a multi-center, randomized, placebo-controlled,double-blind, parallel group study designed to confirm the benefits ofmepolizumab treatment on moderate or severe exacerbations in chronicobstructive pulmonary disease (COPD) participants given as an add on to theiroptimized maintenance COPD therapy. The maximum duration of participantparticipation is approximately 109 weeks, consisting of 2 screening visits (upto 3 weeks), a run-in period (up to 2 weeks), and an intervention period of atleast 52 weeks and up to 104 weeks. 800 participants will be randomized in a1:1 ratio to receive mepolizumab 100 milligrams (mg) or placebo every 4 weeksfor at least 13 doses (52 weeks treatment period) up to a maximum of 26 doses(104 weeks treatment period). The number of randomized participants mayincrease up to approximately 1400.

Detailed Description: Not available

Recruitment & Eligibility

Status: Closed to Recruitment of Participants

Sex: All

Target Recruitment: 800

Inclusion Criteria

Participant must be at least 40 years of age at Screening Visit 1.
Participants with a peripheral blood eosinophil count of more than or equal to 300 cells per microliter (Î¼L) from the hematology sample collected at Screening Visit 0 AND a documented historical blood eosinophil count of more than or equal to 150 cells per Î¼L 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 Screening 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 more than or equal to 150 cells per ÂµL must meet this threshold at the Screening Visit 1 assessment.
Participants with a clinically documented history of COPD for at least 1 year in accordance with the definition by the American Thoracic Society or European Respiratory Society.
Participants must present with a measured pre- and post-salbutamol Forced expiratory volume in one second (FEV1)/Forced vital capacity (FVC) ratio of <0.70 at Screening Visit 1 to confirm the diagnosis of COPD and with a measured post-salbutamol FEV1 less than 20% and less than or equals to 80% of predicted normal values calculated using NHANES III reference equations at Screening Visit 1.
Participants must have a well-documented history (for example, 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.
Participants must have a well-documented requirement for optimized standard of care background therapy that includes inhaled corticosteroids (ICS) plus 2 additional COPD medications (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 1) inhaled corticosteroid at a dose less than or equals to 500 microgram (mcg) per day fluticasone propionate dose equivalent plus 2) Long acting beta2-agonist (LABA) and 3) Long acting muscarinic antagonist (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); inhaled corticosteroid at a dose more than or equal to 500 mcg per day fluticasone propionate dose equivalent plus inhaled LABA or inhaled LAMA and Phosphodiesterase-4-inhibitors, methylxanthines, or scheduled daily use of short acting beta2-agonist (SABA) and/or short acting muscarinic antagonist (SAMA).
Current or former cigarette smokers with a history of cigarette smoking of more than or equal to 10 pack-years at Screening (Visit 1) calculated as (number of pack years equal to [number of cigarettes per day/20] multiplied by number of years smoked [For example, 20 cigarettes per day for 10 years or 10 cigarettes per day for 20 years]).
Contraceptive use for female participant should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: She is not a woman of childbearing potential (WOCBP) or she is a WOCBP and using a contraceptive method that is highly effective, with a failure rate of more than 1%, during the intervention period and for at least 16 weeks after the last dose of study intervention.
The principal investigator (PI) should evaluate the effectiveness of the contraceptive method in relation to the first dose of study intervention.
A WOCBP must have a negative highly sensitive pregnancy urine test within 24 hours before the first dose of study intervention.
If a urine test cannot be confirmed as negative (For example, an ambiguous result), a serum pregnancy test is required.
In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
Participants capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
Participants must meet following randomization inclusion criteria at Visit 2 to be randomized and commence the study intervention period: a) Participants that do not have documented historical blood eosinophil count of more than or equal to 150 cells/Î¼L prior to Screening Visit must meet this threshold based on the Screening Visit 1 assessment, b) Participants must have eosinophil count of more than 300 cells/Î¼L from the hematology sample collected at Screening Visit 0, c) Compliance with completion of the e-diary defined as completion of all questions on 5 or more days out of the 7 days immediately preceding Visit 2.

Exclusion Criteria

Participants with a past history or concurrent diagnosis of asthma are excluded regardless of whether they have active or inactive disease.
The Investigator must judge that COPD is the primary diagnosis accounting for the clinical manifestations of the lung disease.
Participants with alpha1-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.
Participants with pneumonia, COPD exacerbation, or lower respiratory tract infection within the 4 weeks prior to Screening Visit 1.
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.
Participants receiving treatment with oxygen more than 2 liter (L) per minute at rest over 24 hours.
For participants receiving oxygen treatment, participants should demonstrate an oxyhemoglobin saturation greater than or equal to 89percent while breathing supplemental oxygen.
Participants with a QT interval, from the electrocardiogram (ECG) conducted at Screening Visit 1, corrected with Fridericias formula (QTcF) more than 450 millisecond (msec) (or QTcF more than 480 msec in participants with bundle branch block).
Fridericias 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 participants participation during the study, based on the evaluation of the Investigator.
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.
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 or condition exacerbated during the study.
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.
Participants with a known, pre-existing parasitic infestation within 6 months prior to Screening Visit 1.
A current malignancy or previous history of cancer in remission for less than 12 months prior to Screening Visit 1 (participants that had localized carcinoma of the skin or cervix which was resected for cure will not be excluded).
Participants with a known immunodeficiency (For example, human immunodeficiency virus), other than that explained by the use of corticosteroids taken for COPD.
Participants with cirrhosis or current unstable liver disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice.
Stable non-cirrhotic chronic liver disease (including Gilberts syndrome, asymptomatic gallstones, and chronic stable hepatitis B or C e.g., presence of hepatitis B surface antigen (HbsAg) or positive hepatitis C antibody test result) is acceptable if the participant otherwise meets entry criteria.
Participants who have received interventional product in previous mepolizumab studies are excluded.
Participants who have received any monoclonal antibody within 5 half-lives of Screening Visit 1.
Participants who have received an investigational drug within 30 days of Visit 1, or within 5 drug half-lives of the investigational drug, whichever is longer (this also includes investigational formulations of a marketed product).
Participants who have received short term use of oral corticosteroids within 30 days of Visit 1.
Participants with a known allergy or sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the Investigator or Medical Monitor, contraindicates participation in the study or intolerance to another monoclonal antibody or biologic including history of anaphylaxis to another biologic.
Participants at risk of non-compliance, or unable to comply with the study procedures.
Any infirmity, disability, or geographic location that would limit compliance for scheduled visits.
Participants with conditions that will limit the validity of informed consent to participate in the study, for example, uncontrolled psychiatric disease or intellectual deficiency.
Participants with a known or suspected history of alcohol or drug abuse within 2 years prior to Visit 1.
Participant is an Investigator, sub-Investigator, study coordinator, employee of a participating Investigator or study site, or immediate family member of the aforementioned that is involved in this study.
Participant will not be randomized if they meet any of the following randomization exclusion criteria at Visit 2 a) Participants who have pneumonia, exacerbation, lower respiratory infection during the Run-in period.
b) Evidence of clinically significant abnormality in the hematological or biochemical screen at Visit 1, as judged by the Investigator.
c) Participants who meet the following based on results from sample taken at Screening Visit 1 Alanine aminotransferase (ALT) more than 2x upper limit of normal (ULN), bilirubin more than 1.5 x ULN (isolated bilirubin more than 1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin less than 35percent), cirrhosis or current unstable liver or biliary disease per Investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, or persistent jaundice.
d) Participants who are pregnant or breastfeeding.
Participants should not be randomized if they plan to become pregnant during the time of study participation.
e) Participants that had an active COVID-19 infection during the Run-in period, either laboratory confirmed or according to the investigators medical judgment or known to be in contact with active COVID-19 positive individuals within the past 14 days.
f) Participants with a QT interval, from the ECG conducted at Visit 2, corrected with Fridericias formula (QTcF) more than 450 msec (or QTcF more than 480 msec in participants with bundle branch block).

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To evaluate the efficacy of mepolizumab 100 mg subcutaneous (SC) compared to placebo, given every 4 weeks in liquid formulation by safety syringe (SS) to COPD participants at high risk of exacerbations despite the use of optimized COPD maintenance therapy.	Annualized rate of moderate/severe exacerbations. \| Up to Week 104

Secondary Outcome Measures

Name	Time	Method
To evaluate mepolizumab 100 mg SC compared to placebo given every 4 weeks in liquid formulation by SS on additional efficacy assessments, health related quality of life (HRQoL), health care utilization, and symptoms	Time to first moderate/severe exacerbation. Up to Week 104

Trial Locations

Locations (14): Apollo Spectra Hospital
🇮🇳
Nagar, UTTAR PRADESH, India
Aster Prime Hospital
🇮🇳
Hyderabad, TELANGANA, India
Care Institute of Medical Sciences
🇮🇳
Ahmadabad, GUJARAT, India
Criticare Hospital and Research Institute
🇮🇳
Nagpur, MAHARASHTRA, India
Dr B L Kapur Memorial Hospital
🇮🇳
Delhi, DELHI, India
Getwell Hospital and Research Institute
🇮🇳
Nagpur, MAHARASHTRA, India
Jawaharlal Nehru Medical College
🇮🇳
Aligarh, UTTAR PRADESH, India
Jaydeep Hospital
🇮🇳
Ahmadabad, GUJARAT, India
M V Hospital and Research Center
🇮🇳
Lucknow, UTTAR PRADESH, India
Maharaja Agrasen Superspecialty Hospital
🇮🇳
Jaipur, RAJASTHAN, India
Scroll for more (4 remaining)
Apollo Spectra Hospital
🇮🇳Nagar, UTTAR PRADESH, India
Dr Sandeep Katiyar
Principal investigator
9889888181
skkatiyar_in@yahoo.com