A Study to Determine Long-term Safety of Mepolizumab in Asthmatic Subjects

This study is currently recruiting participants.
Verified December 2013 by GlaxoSmithKline
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01842607
First received: April 25, 2013
Last updated: January 2, 2014
Last verified: December 2013
  Purpose

This is a multi-centre, open-label long-term safety study of 100 milligram (mg) mepolizumab administered subcutaneously (SC) every 4 weeks for 12 months in addition to standard of care in subjects who have severe, refractory asthma and a history of eosinophilic inflammation. Subjects who completed either MEA115588 or MEA115575 will be offered the opportunity to consent for this study.


Condition Intervention Phase
Asthma
Biological: Mepolizumab
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: MEA115661: A Multi-centre, Open-label, Long-term Safety Study of Mepolizumab in Asthmatic Subjects Who Participated in the MEA115588 or MEA115575 Trials

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of subjects with Adverse Events (AEs) [ Time Frame: Up to 64 weeks ] [ Designated as safety issue: No ]
    AEs including non- serious and serious adverse events (SAEs). An AE is any untoward medical occurrence temporally associated with the use of the medicinal product, whether or not considered associated with the product. A serious AE is any medical occurrence that results in death, is life-threatening, require hospitalization or prolongation of an existing hospital stay, results in disability or incapacity, congenital anomaly, or is an "Hy's Law event (type of drug-induced liver injury)

  • Frequency of adverse events both systemic (i.e., allergic and non-allergic) and local site reactions [ Time Frame: Up to 64 weeks ] [ Designated as safety issue: No ]
    Safety monitoring including allergic, non-allergic and local site reactions are reported after the first 3 doses.

  • Number of subject withdrawals due to AEs [ Time Frame: Up to 64 weeks ] [ Designated as safety issue: No ]
  • Number of subjects hospitalized due to AEs including asthma exacerbations [ Time Frame: Up to 64 weeks ] [ Designated as safety issue: No ]
    Exacerbations is defined as worsening of asthma which requires use of systemic corticosteroids and/or hospitalisation and/or emergency department visits

  • 12-Lead ECG measurements to assess safety [ Time Frame: Up to 64 weeks ] [ Designated as safety issue: No ]
    Electrocardiogram (ECG) measurements include QT and QTc interval, it will be made after the subject has rested in the supine position for 5 minutes. Mean change from baseline in the QTc(F) (QT interval corrected by Friderica's method) Mean change from baseline in QTc(B) (QT interval corrected by Bazett's method), Maximum change from baseline for QTc(F) and QTc(B) will be measured.

  • Vital signs measurements to assess safety [ Time Frame: Up to 64 weeks ] [ Designated as safety issue: No ]
    Vital signs including sitting pulse rate and blood pressure measurements

  • Clinical laboratory measurements to assess safety [ Time Frame: Up to 64 weeks ] [ Designated as safety issue: No ]
    Clinical laboratory tests as measured by abnormal parameters for hematology and clinical chemistry


Secondary Outcome Measures:
  • Frequency of positive anti-mepolizumab binding antibodies and neutralizing antibodies [ Time Frame: Up to 64 weeks ] [ Designated as safety issue: No ]
    Blood samples will be collected for the determination of anti-mepolizumab antibodies, just prior to administration of mepolizumab. Samples testing positive for anti-mepolizumab antibodies will be further tested for neutralising antibody

  • Annualized rate of exacerbations [ Time Frame: Up to 64 weeks ] [ Designated as safety issue: No ]
    Exacerbations are defined as worsening of asthma which requires use of systemic corticosteroids and/or hospitalisation and/or emergency department visits

  • Asthma Control Questionnaire score (ACQ) [ Time Frame: Up to 64 weeks ] [ Designated as safety issue: No ]
    The ACQ-5 is a five-item questionnaire. Five questions are scored on a six point scale. (0= no impairment/limitation, 6= total impairment/ limitation). Total score range from 0 to 30. Higher score indicates greater impairment

  • FEV1 measured by clinic spirometry [ Time Frame: Up to 52 weeks ] [ Designated as safety issue: No ]
    Forced Expiratory Volume in 1 second (FEV1) is the maximal amount of air that can be forcefully exhaled in one second

  • Number of subject withdrawals due to lack of efficacy [ Time Frame: Up to 64 weeks ] [ Designated as safety issue: No ]
    Number of subject withdrawals due to lack of efficacy are summarized


Estimated Enrollment: 660
Study Start Date: May 2013
Estimated Study Completion Date: April 2016
Estimated Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Mepolizumab Arm
Subjects will receive 100 mg of Mepolizumab (in polypropylene syringe) injected subcutaneously (SC) once every 4 weeks for 12 months
Biological: Mepolizumab
Mepolizumab (a fully humanised IgG antibody) 100 mg injected SC once every 4 weeks for 12 months. Mepolizumab will be provided as a lyophilised cake in sterile vials

  Eligibility

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.
  • Informed Consent: Prior to commencing any study related activities, subjects must be able and willing to provide written informed consent.
  • MEA115588 or MEA115575 study completion: Completion of the double-blind investigational product treatment during MEA115588 or MEA115575.
  • Current Anti-Asthma Therapy: Asthma is currently being treated with a controller medication (i.e., inhaled corticosteroids [ICS] or other asthma controlled medication) and the subject has been on a controller medication for the past 12 weeks. Subjects will be expected to continue controller therapy for the duration of the study.
  • Male or eligible female subjects:
  • To be eligible for entry into the study, females of childbearing potential must commit to consistent and correct use of an acceptable method of birth control for the duration of the trial and for 4 months after the last study drug administration.
  • A serum pregnancy test is required of all females at the initial Baseline Visit (Visit 1). In addition, a urine pregnancy test will be performed for all females prior to enrollment, during each scheduled study visit prior to the injection of investigational product, and during the Follow-up Visit.

Exclusion Criteria:

  • Hypersensitivity: Hypersensitivity reaction related to study medication during the MEA115588 or MEA115575 that led to patient withdrawal. Subjects who experienced a localized injection site reaction do not need to be excluded.
  • Health Status: Clinically significant change in health status during MEA115588 or MEA115575 which in the opinion of the investigator would make the subject unsuitable for participation in this long-term study.
  • Malignancy: A current malignancy or malignancy that developed during MEA115588 or MEA115575 (subjects that had localized carcinoma of the skin which was resected for cure will not be excluded). [Note for South Korea: Korean subjects with a diagnosis of malignancy within 5 years are excluded]
  • Prior SAE: A study related SAE in MEA115588 or MEA115575 that was assessed as possibly related to study medication by the investigator.
  • Pregnancy: Subjects who are pregnant or breastfeeding. Subjects should not be enrolled if they plan to become pregnant during the time of study participation.
  • ECG: Baseline ECG which has a clinically significant abnormality or which shows corrected QT interval with Fridericia (QTcF) >=450 millisecond (msec) or QTcF >=480 msec for subjects with Bundle Branch Block.
  • Smoking status: Current smokers
  • Liver Function: Liver function tests that meet any of the following during one of the last treatment visits in MEA115588 or MEA115575 : alanine transaminase (ALT) >=2 x upper limit of normal (ULN); aspartate transaminase (AST) >=2 x ULN; alkaline phosphatase >=2 x ULN; Bilirubin >1.5 x ULN (isolated bilirubin >1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin is <35%
  • Hepatitis Status: Positive Hepatitis B Surface Antigen (HBsAg) screen at Visit 1
  • ECG Over-read: Clinically significant abnormality identified during the central over-read during one of the last treatment visits in MEA115588 or MEA115575
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01842607

Contacts
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com

  Show 135 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01842607     History of Changes
Other Study ID Numbers: 115661
Study First Received: April 25, 2013
Last Updated: January 2, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
eosinophils
mepolizumab
SB-240563
safety
extension study
Severe refractory asthma

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases

ClinicalTrials.gov processed this record on April 22, 2014