CClinicalTrials.gg
CompletedNCT03298061Updated Mar 12, 2024Results posted

Long-term Access Program (LAP) of Mepolizumab for Subjects Who Participated in Study MEA115921

A Phase 3 interventional study of Mepolizumab and Prednisolone in Churg-Strauss Syndrome and Eosinophilic Granulomatosis With Polyangiitis, sponsored by GlaxoSmithKline. Completed at 32 sites in 7 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-03-12.

Sponsored by GlaxoSmithKline · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
100
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study summary

Eosinophilic Granulomatosis with Polyangiitis (EGPA), also referred to as Churg-Strauss syndrome, is a rare hyper-eosinophilic syndrome. Eosinophilia is central to the pathophysiology of EGPA and interleukin-5 (IL-5) is a key cytokine regulating the life-cycle of the eosinophil. Neutralization of IL-5 with mepolizumab, an anti-IL5 monoclonal antibody, therefore offers a potential therapeutic option for EGPA. The objective of study MEA115921 was to investigate the efficacy and safety of mepolizumab compared with placebo wherein the subjects were randomized to receive either: 300 milligram (mg) mepolizumab or Placebo subcutaneous (SC) injection every 4 weeks in addition to their background standard-of-care therapy. Subjects were treated for a period of 52 weeks and then followed up for a further 8 weeks to study completion at Week 60. This is a LAP to support provision of open-label mepolizumab on an individual basis to eligible subjects who participated in clinical study MEA115921 and who require a dose of prednisolone (or equivalent) of >=5 milligrams per day (mg/day) for adequate control of their EGPA. Eligible subjects can initiate mepolizumab under this LAP within a 6-month period starting from completion of study MEA115921 (that is, at Week 60) or, in case of premature discontinuation from study MEA115921, the subjects will initiate mepolizumab at the time point that would have been Week 60 if the subject had completed the study. Eligible subjects will receive subcutaneously administered mepolizumab at a dose of 300 mg SC every 4 weeks. Eligible subjects will continue to receive mepolizumab under this LAP until mepolizumab is commercially licensed for the treatment of EGPA in the relevant country or until GlaxoSmithKline (GSK) discontinues the program or until the subject meets any of the withdrawal/stopping criteria.

02

Conditions studied

  • Churg-Strauss Syndrome
  • Eosinophilic Granulomatosis With Polyangiitis

Keywords

  • Eosinophilic Granulomatosis
  • MEA115921
  • Polyangiitis
  • Long-term access program
  • mepolizumab
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Subject participated in study MEA115921.
  • Subject has either: a) completed study MEA115921 to Week 60, that is, completion of follow up period, or b) if the subject was withdrawn prematurely from study MEA115921, the subject has reached the date of what would have been the Week 60 if the subject had completed the study, that is, 60 weeks from Baseline (Visit 2).
  • At or up to 6 months after the MEA115921 Week 60 time- point the subject requires a dose of prednisolone (or equivalent) of >=5 mg/day for adequate control of their EGPA.
  • The treating physician requesting mepolizumab under this LAP considers the benefits of treatment with mepolizumab outweigh the risks for the individual subject.
  • To be eligible for mepolizumab treatment under this LAP, females of childbearing potential (FCBP) must commit to consistent and correct use of an acceptable method of birth control, beginning with consent, for the duration of the treatment with mepolizumab and for 4 months after the last mepolizumab administration.
  • The subject consents to receiving treatment with mepolizumab under this LAP.

Exclusion criteria

Exclusion Criteria:

  • A current malignancy or history of cancer in remission for less than 12 months (Subjects who had localized carcinoma (that is, basal or squamous cell) of the skin which was resected for cure will not be excluded).
  • Subject has other clinically significant medical conditions uncontrolled with standard of care therapy not associated with EGPA, example, unstable liver disease, uncontrolled cardiovascular disease, ongoing active infectious disease requiring systemic treatment.
  • Subject is pregnant or breastfeeding. Subjects should not be considered for continued treatment if they plan to become pregnant during the course of treatment with mepolizumab.
  • Subject has a known allergy or intolerance to a monoclonal antibody or biologic therapy including mepolizumab.
  • Subject had an adverse event (serious or non-serious) considered related to study treatment whilst participating in study MEA115921 which resulted in permanent withdrawal of study treatment.
  • Subject is receiving treatment with another biological therapy such as a monoclonal antibody therapy or intravenous (IV) immunoglobulin therapy without prior agreement from the GSK Medical Monitor.
  • Subjects who have received treatment with an investigational drug within the past 30 days or 5 terminal phase half-lives of the drug whichever is longer, prior to initiation of mepolizumab treatment under this LAP (this also includes investigational formulations of marketed products).
  • Subject is currently participating in any other interventional clinical study.
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
100 participants (actual)

Study arms

  • Experimental
    Subjects from clinical study MEA115921

    Subjects who participated in clinical study MEA115921 and who require a dose of prednisolone (or equivalent) of 5 mg/day for adequate control of their EGPA will be included. Eligible subjects will receive subcutaneously administered mepolizumab at a dose of 300 mg SC every 4 weeks.

    Drug: Mepolizumab · Drug: Prednisolone

Interventions

  • DrugMepolizumab

    Mepolizumab will be available as lyophilized powder for injection to be reconstituted with sterile water for injection, prior to use. Subjects will be dosed with mepolizumab at a dose of 300 mg which will be administered as three separate 100 mg SC injections every 4 weeks. The injections will be administered into any of the upper arm, thigh or anterior abdominal wall.

  • DrugPrednisolone

    Subjects who require a dose of prednisolone (or equivalent) of 5 mg/day for adequate control of their EGPA will be included.

05

What researchers measure

Primary outcomes

  1. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

    An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; is a congenital anomaly/birth defect; other important medical events based on medical or scientific judgment; and is associated with liver injury and impaired liver function. Additionally, systemic (that is, allergic/hypersensitivity and non-allergic) reactions and local injection site reactions were recorded throughout the treatment and follow-up period.

    Time frame: Up to approximately 89 Months

06

Results

Posted Mar 12, 2024

Participant flow

Participants who participated in clinical study MEA115921 and required a dose of prednisolone (or equivalent) of greater than or equal to (\>=) 5 milligrams per day (mg/day) for adequate control of their Eosinophilic Granulomatosis with Polyangiitis (EGPA) were included in this study based on their eligibility. Eligible participants received subcutaneous (SC) injection of mepolizumab 300 milligrams (mg) every 4 weeks.

Participant flow — Overall Study
MilestoneMepolizumab 300 mg
Started100
Completed73
Not completed27
Withdrew: Adverse event3
Withdrew: Lack of efficacy6
Withdrew: Protocol violation1
Withdrew: Physician decision7
Withdrew: Withdrawal by subject10

Outcome measures

PrimaryNumber of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; is a congenital anomaly/birth defect; other important medical events based on medical or scientific judgment; and is associated with liver injury and impaired liver function. Additionally, systemic (that is, allergic/hypersensitivity and non-allergic) reactions and local injection site reactions were recorded throughout the treatment and follow-up period.

Time frame:
Up to approximately 89 Months
Reported as:
Count of participants · Participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
ParticipantsMepolizumab 300 mg
AE98
SAE38

Adverse events

Collected over Up to approximately 89 Months. Non-serious events are listed at a 3% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Mepolizumab 300 mg1/100 (1%)38/100 (38%)97/100 (97%)
Most frequent serious events
Showing 10 of 64
Most frequent serious events
EventMepolizumab 300 mg
AsthmaRespiratory, thoracic and mediastinal disorders6/100
Eosinophilic granulomatosis with polyangiitisImmune system disorders3/100
PneumoniaInfections and infestations3/100
Atrial fibrillationCardiac disorders2/100
Myocardial infarctionCardiac disorders2/100
BronchitisInfections and infestations2/100
CellulitisInfections and infestations2/100
GastroenteritisInfections and infestations2/100
InfluenzaInfections and infestations2/100
SepsisInfections and infestations2/100
Most frequent other events
Showing 10 of 83
Most frequent other events
EventMepolizumab 300 mg
NasopharyngitisInfections and infestations33/100
Upper respiratory tract infectionInfections and infestations31/100
SinusitisInfections and infestations30/100
BronchitisInfections and infestations29/100
AsthmaRespiratory, thoracic and mediastinal disorders26/100
ArthralgiaMusculoskeletal and connective tissue disorders20/100
Back painMusculoskeletal and connective tissue disorders16/100
RashSkin and subcutaneous tissue disorders15/100
DiarrhoeaGastrointestinal disorders14/100
NauseaGastrointestinal disorders14/100

Baseline characteristics

Age, Continuous
Age, Continuous(YEARS)Mepolizumab 300 mg
Mean49.6 ± 13.90
Sex: Female, Male
Sex: Female, Male(Participants)Mepolizumab 300 mg
Female57
Male43
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Mepolizumab 300 mg
AMERICAN INDIAN OR ALASKA NATIVE1
ASIAN - JAPANESE HERITAGE6
ASIAN - SOUTH EAST ASIAN HERITAGE2
WHITE - ARABIC/NORTH AFRICAN HERITAGE1
WHITE - WHITE/CAUCASIAN/EUROPEAN HERITAGE90
07

Study locations

32 sites
  • GSK Investigational Site
    Denver, Colorado 80206, United States
  • GSK Investigational Site
    Bethesda, Maryland 20892, United States
  • GSK Investigational Site
    Boston, Massachusetts 02118-2307, United States
  • GSK Investigational Site
    Boston, Massachusetts 02215, United States
  • GSK Investigational Site
    Saint Louis, Missouri 63110, United States
  • GSK Investigational Site
    New York, New York 10021, United States
  • GSK Investigational Site
    Cleveland, Ohio 44195, United States
  • GSK Investigational Site
    Oklahoma City, Oklahoma 73131, United States
  • GSK Investigational Site
    Philadelphia, Pennsylvania 19104, United States
  • GSK Investigational Site
    Mempis, Tennessee 38119, United States
  • GSK Investigational Site
    Murray, Utah 84107, United States
  • GSK Investigational Site
    Saint George, Utah 84770, United States
  • GSK Investigational Site
    Abingdon, Virginia 24210, United States
  • GSK Investigational Site
    Bellevue, Washington 98004, United States
  • GSK Investigational Site
    Bruxelles, 1070, Belgium
  • GSK Investigational Site
    Hamilton, Ontario L8N 4A6, Canada
  • GSK Investigational Site
    Bron Cedex, 69677, France
  • GSK Investigational Site
    Marseille Cedex 20, 13915, France
  • GSK Investigational Site
    Montpellier cedex 5, 34295, France
  • GSK Investigational Site
    Paris, 75014, France
  • GSK Investigational Site
    Saint-Priest en Jarez, 42270, France
  • GSK Investigational Site
    Suresnes, 92151, France
  • GSK Investigational Site
    Freiburg, Baden-Wuerttemberg 79106, Germany
  • GSK Investigational Site
    Kirchheim -Teck, Baden-Wuerttemberg 73230, Germany
  • GSK Investigational Site
    Fulda, Hessen 36043, Germany
  • GSK Investigational Site
    Bad Bramstedt, Schleswig-Holstein 24576, Germany
  • GSK Investigational Site
    Jena, Thueringen 07740, Germany
  • GSK Investigational Site
    Kanagawa, 252-0392, Japan
  • GSK Investigational Site
    Miyagi, 980-8574, Japan
  • GSK Investigational Site
    Portsmouth, Hampshire PO6 3LY, United Kingdom
  • GSK Investigational Site
    Cambridge, CB2 0QQ, United Kingdom
  • GSK Investigational Site
    Leicester, LE3 9QP, United Kingdom
08

References and documents

Study documents

  • Study protocol · Jun 30, 2021
  • Statistical analysis plan · Aug 1, 2019

Documents are hosted by the registry — open the source record to download them.

09

Registry details

Key details

Study ID
NCT03298061
Lead sponsor
GlaxoSmithKline
Responsible party
Sponsor
First posted
Sep 29, 2017
Start date
Apr 14, 2015
Primary completion
Feb 16, 2023
Completion
Feb 16, 2023
Results posted
Mar 12, 2024
Last update
Mar 12, 2024

Study contacts

GSK Clinical Trials
study director · GlaxoSmithKline

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
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