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Mepolizumab as Add-on Treatment IN Participants With COPD Characterized by Frequent Exacerbations and Eosinophil Level (MATINEE)

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ClinicalTrials.gov Identifier: NCT04133909
Recruitment Status : Recruiting
First Posted : October 21, 2019
Last Update Posted : November 18, 2019
Sponsor:
Collaborator:
PPD
Information provided by (Responsible Party):
GlaxoSmithKline

Tracking Information
First Submitted Date  ICMJE October 18, 2019
First Posted Date  ICMJE October 21, 2019
Last Update Posted Date November 18, 2019
Actual Study Start Date  ICMJE October 30, 2019
Estimated Primary Completion Date January 13, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 18, 2019)
Annualized rate of moderate or severe exacerbations [ Time Frame: Up to Week 52 ]
Moderate exacerbations are defined as clinically significant exacerbations that require treatment with oral or systemic corticosteroids and/or antibiotics. Severe exacerbations are defined as clinically significant exacerbations that require in-patient hospitalization (>=24 hours) or result in death. The frequency of moderate or severe exacerbations expressed as an annualized exacerbation rate will be evaluated.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT04133909 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 18, 2019)
  • Time to first moderate or severe exacerbation [ Time Frame: Up to Week 52 ]
    Moderate exacerbations are defined as clinically significant exacerbations that require treatment with oral or systemic corticosteroids and/or antibiotics. Severe exacerbations are defined as clinically significant exacerbations that require in-patient hospitalization (>=24 hours) or result in death.
  • Number of COPD assessment test (CAT) responders [ Time Frame: Week 52 ]
    The proportion of CAT score responders with reduction of >=2 units in CAT score from Baseline will be assessed.
  • Number of St. George's Respiratory Questionnaire (SGRQ) total score responders [ Time Frame: Week 52 ]
    The proportion of SGRQ total score responders with reduction of >=4 units in SGRQ total score from Baseline will be assessed. It will be calculated using St. George's Respiratory Questionnaire for COPD (SGRQ-C).
  • Number of Evaluating Respiratory Symptoms in COPD (E-RS: COPD) responders [ Time Frame: Week 52 ]
    The proportion of E-RS: COPD responders with reduction of >=2 units in E-RS: COPD total score from Baseline will be assessed.
  • Annualized rate of exacerbations requiring Emergency Department (ED) visit or hospitalization [ Time Frame: Up to Week 52 ]
    Annualized rate of exacerbations requiring ED visit or hospitalization will be evaluated.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Mepolizumab as Add-on Treatment IN Participants With COPD Characterized by Frequent Exacerbations and Eosinophil Level (MATINEE)
Official Title  ICMJE 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)
Brief Summary This is a multi-center, randomized, placebo-controlled, double-blind, parallel group study designed to confirm the benefits of mepolizumab treatment on moderate or severe exacerbations in COPD participants given as an add on to their optimized maintenance COPD therapy. The maximum duration of participant participation is approximately 57 weeks, consisting of 2 screening visits, run-in period, and a 52-week intervention period. 800-1000 participants will be randomized in 1:1 ratio to receive mepolizumab 100 milligram (mg) or placebo every 4 weeks for a total of 13 doses.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Pulmonary Disease, Chronic Obstructive
Intervention  ICMJE
  • Drug: Placebo
    Placebo is a 0.9% sodium chloride solution. It will be administered as a subcutaneous (SC) injection delivered once every 4 weeks using a pre-filled safety syringe.
  • Biological: Mepolizumab
    Mepolizumab is a sterile liquid formulation. It will be administered as a SC injection (100 mg/mL) delivered once every 4 weeks using a pre-filled safety syringe.
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    Participants will receive placebo subcutaneously once every 4 weeks over a treatment period of 52 weeks.
    Intervention: Drug: Placebo
  • Experimental: Mepolizumab
    Participants will receive mepolizumab subcutaneously once every 4 weeks over a treatment period of 52 weeks.
    Intervention: Biological: Mepolizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 18, 2019)
800
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 13, 2023
Estimated Primary Completion Date January 13, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Participant must be at least 40 years of age at Screening Visit 1.
  • Participants with a peripheral blood eosinophil count of >=300 cells per microliter (μL) from the hematology sample collected at Screening Visit 0. Participants with a documented historical blood eosinophil count of >=150 cells per 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 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 >=150 cells per µL 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>20% and <=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 >=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 >=500 microgram 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 >=10 pack-years at Screening (Visit 1) calculated as (number of pack years = [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 <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.

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.
  • 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 89% while breathing supplemental oxygen.
  • Participants with a QT interval, from the ECG conducted at Screening Visit 1, corrected with Fridericia's formula (QTcF) >450 millisecond (msec) (or QTcF >480 msec in participants with bundle branch block). Fridericia's 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.
  • 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/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 [HIV]), 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 Gilbert's 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 40 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 89904466 GSKClinicalSupportHD@gsk.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04133909
Other Study ID Numbers  ICMJE 208657
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
URL: http://clinicalstudydatarequest.com
Responsible Party GlaxoSmithKline
Study Sponsor  ICMJE GlaxoSmithKline
Collaborators  ICMJE PPD
Investigators  ICMJE
Study Director: GSK Clinical Trials GlaxoSmithKline
PRS Account GlaxoSmithKline
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP