Trial record 1 of 187040 for:    ALL
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A Phase 3a, Repeat Dose, Open-label, Long-term Safety Study of Mepolizumab in Asthmatic Subjects

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2015 by GlaxoSmithKline
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT02135692
First received: May 8, 2014
Last updated: March 26, 2015
Last verified: March 2015
  Purpose

This is a multi-center, open-label, long-term study of subcutaneously (SC) administered mepolizumab 100mg in addition to standard of care (SOC), in subjects with severe eosinophilic asthma. This study will enroll a subset of subjects from Study MEA115661 who have demonstrated clear benefit from therapy and who without continuation of mepolizumab therapy are individuals at greatest risk of serious deterioration of their health status. In order to target individuals at greatest risk for serious deterioration of their health status, only subjects from the MEA115661 study with a history of life-threatening or seriously debilitating asthma, will be allowed to participate. Subjects meeting all of the eligibility criteria for the study will be offered the opportunity to consent for this study of up to 128 weeks in length (including the Follow-Up Visit). This study will give opportunity to extend the collection of clinical data for long-term use and further assess the sustainability of efficacy in a population likely to experience significant loss of asthma control and the need for higher doses of systemic steroids if returned to SOC only.


Condition Intervention Phase
Asthma
Biological: Mepolizumab
Drug: SOC
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Study 201312: A Multi-Centre, Open-Label, Study of Mepolizumab in a Subset of Subjects With a History of Life Threatening/Seriously Debilitating Asthma Who Participated in the MEA115661 Trial

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Annualized rate of exacerbations [ Time Frame: Up to Weeks 128 ] [ Designated as safety issue: No ]
    Exacerbations will be defined as worsening of asthma which requires use of systemic corticosteroids (CS) and/or hospitalisation and/or emergency department (ED) visits.

  • Frequency of all adverse events (AEs) [ Time Frame: Up to Weeks 128 ] [ Designated as safety issue: No ]
    Descriptive analysis of the safety profile of mepolizumab.


Secondary Outcome Measures:
  • Frequency of positive anti-mepolizumab binding antibodies/neutralizing antibodies [ Time Frame: Up to Weeks 128 ] [ 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.

  • Asthma Control Questionnaire-5 score [ Time Frame: Up to Weeks 128 ] [ Designated as safety issue: No ]
    The Asthma Control Questionnaire-5 (ACQ-5) is a five-item questionnaire used to measures a subject's asthma control.

  • Forced expiratory volume in 1 second (FEV1) [ Time Frame: Up to Weeks 128 ] [ Designated as safety issue: No ]
    FEV1 is a measure of lung function.

  • Number of withdrawals due to lack of efficacy [ Time Frame: Up to Weeks 128 ] [ Designated as safety issue: No ]
    The number of subject withdrawals due to lack of efficacy will be summarized.

  • Number of withdrawals due to AEs [ Time Frame: Up to Weeks 128 ] [ Designated as safety issue: No ]
    The number of subject withdrawals due to adverse events will be summarized.

  • Number of hospitalizations due to AEs including asthma exacerbations [ Time Frame: Up to Weeks 128 ] [ Designated as safety issue: No ]
    The number of subject hospitalizations due to adverse events or exacerbations will be summarized.

  • Frequency of both systemic (i.e., allergic and non-allergic) and local site reactions [ Time Frame: Up to Weeks 128 ] [ Designated as safety issue: No ]
    A summary of AEs of special interest.

  • 12 lead ECG parameters [ Time Frame: Up to Weeks 128 ] [ Designated as safety issue: No ]
    A summary of the mean changes in specific safety ECG parameters from baseline.

  • Safety as assessed by vital signs [ Time Frame: Up to Weeks 128 ] [ Designated as safety issue: No ]
    Vital signs including sitting pulse rate and blood pressure measurements.

  • Safety as assessed by clinical laboratory parameters [ Time Frame: Up to Weeks 128 ] [ Designated as safety issue: No ]
    Clinical laboratory tests as measured by parameters for hematology and clinical chemistry.


Estimated Enrollment: 375
Study Start Date: May 2014
Estimated Study Completion Date: September 2017
Estimated Primary Completion Date: September 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Mepolizumab 100 mg
All subjects will receive mepolizumab 100mg administered SC into the upper arm or thigh approximately every 4 weeks.
Biological: Mepolizumab
Mepolizumab is a fully humanised IgG antibody (IgG1, kappa) with human heavy and light chain frameworks. Mepolizumab will be supplied as a lyophilised cake in sterile vials for individual use.
Drug: SOC
Standard of Care (SOC) will differ by participant, however it will generally include oral corticosteroids and an inhaled controller medicine (an inhaled corticosteroid plus a long acting beta agonist) and/or short acting beta agonists

  Eligibility

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

Inclusion Criteria:

  • Informed Consent: Prior to commencing any study related activities, subjects must be able and willing to provide written informed consent.
  • Male or Eligible Female Subjects: To be eligible for the study, females of child-bearing potential must commit to consistent and correct use of an acceptable method of birth control and for 4 months after the last study drug administration. A urine pregnancy test is required of all females of childbearing potential at the initial Baseline Visit (Visit 1).
  • French Subjects Only: 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.
  • MEA115661 Participation: Subjects must have completed Visit 14 of MEA115661.
  • Current Anti-Asthma Therapy: The subject's asthma has been treated with an ICS controller medication for the last 8 months with fluticasone propionate (FP) >=500 mcg/day (or equivalent).
  • Disease Severity: Subjects must be assessed as having life-threatening /serious debilitating asthma in order to enroll, as defined by the following: Subjects enrolled in MEA115588 must meet one of the following criteria: a) Subject has a history of at least one intubation during their lifetime; b) >=3 asthma exacerbations in the 12 months prior to screening for MEA115588; c) >=1 or more hospitalization for asthma exacerbation in the 12 months prior to screening for MEA115588. Subjects enrolled in MEA115575 must meet one of the following criteria: d) Subject has a history of at least one intubation during their lifetime; e) Their optimized dose at randomization in MEA115575 was >=10mg of prednisone; f) >=1 or more hospitalization for asthma exacerbation in the 12 months prior to screening for MEA115575.
  • Clinical Benefit: Subjects must have experienced documented clinical benefit to enroll. Subjects must meet the following criteria demonstrating clinical benefit: Subjects enrolled in MEA115588 who received mepolizumab must meet all of the following criteria: a) Subject must have had a reduction in their exacerbation frequency by >=50% during MEA115588. The baseline for comparison is the total number of exacerbations reported in the 12 months prior to screening for MEA115588. b) The investigator response on the "Clinician-Rated Response to Therapy" questionnaire at Visit 10 was either: mildly improved, moderately improved or significantly improved. Subjects enrolled in MEA115588 who received placebo must meet all of the following criteria: c) Subject must have had a reduction in their exacerbation frequency by >=50% during the first 8 months of MEA115661. The baseline for comparison is the total number of exacerbations reported in the 12 months prior to screening for MEA115588; d) The investigator confirms that the subject demonstrated improvement during MEA115661. Subjects enrolled in MEA115575 who received mepolizumab must meet all of the following criteria: e) Subject must have reduced their oral corticosteroid dose by >=50% during MEA115575. The baseline for comparison is the subject's optimized oral corticosteroid (OCS) dose at randomization in MEA115575; f) The investigator response on the "Clinician-Rated Response to Therapy" questionnaire at Visit 9 was either: mildly improved, moderately improved or significantly improved. Subjects enrolled in MEA115575 who received placebo must meet all of the following criteria: g) Subject must have reduced their oral corticosteroid dose at randomization by >=50% in the first 6 months of MEA115661. The baseline for comparison is the subject's optimized OCS dose at randomization in MEA115575; h) The investigator confirms that the subject demonstrated improvement during MEA115661.

Exclusion Criteria

  • Health Status: Clinically significant change in health status during MEA115661 which in the opinion of the investigator would make the subject unsuitable for participation in this long-term study.
  • Pregnancy: Subjects who are pregnant or breastfeeding. Subjects should not be enrolled if they plan to become pregnanDeart during the time of study participation.
  • Exacerbation History: Subjects who received placebo in MEA115588 and had NO exacerbations during the study.
  • Oral Corticosteroid Use: Subjects who received placebo in MEA115575 and were able to discontinue oral corticosteroid therapy by the end of the study.
  • Smoking Status: Current smokers
  • Previous Significant Protocol Deviation: Subjects who were excluded from the per protocol analysis due to significant protocol deviations in either study MEA115575 or MEA115588.
  • Electrocardiogram (ECG) Assessment: A clinically significant ECG abnormality at the exit visit of MEA115661, as determined by the investigator.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02135692

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

  Show 109 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT02135692     History of Changes
Other Study ID Numbers: 201312
Study First Received: May 8, 2014
Last Updated: March 26, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
Extension study
Safety
Eosinophils
Mepolizumab
Expanded access
Severe eosinophilic asthma

ClinicalTrials.gov processed this record on March 26, 2015