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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01691508




Registration number
NCT01691508
Ethics application status
Date submitted
20/09/2012
Date registered
24/09/2012
Date last updated
23/03/2017

Titles & IDs
Public title
Mepolizumab Steroid-Sparing Study in Subjects With Severe Refractory Asthma
Scientific title
MEA115575: A Randomised, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study of Mepolizumab Adjunctive Therapy to Reduce Steroid Use in Subjects With Severe Refractory Asthma
Secondary ID [1] 0 0
115575
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Asthma 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Asthma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Mepolizumab
Treatment: Drugs - Placebo
Treatment: Drugs - OCS (prednisone/prednisolone)

Experimental: Mepolizumab - Mepolizumab 100 mg subcutaneous once every 4 weeks upto Week 20

Experimental: Placebo - Placebo subcutaneous once every 4 weeks upto Week 20


Treatment: Drugs: Mepolizumab
Mepolizumab is a fully humanised Immunoglobulin G antibody (IgG1, kappa) with human heavy and light chain frameworks.

Treatment: Drugs: Placebo
Will be available as an equivalent volume of 0.9% sodium chloride.

Treatment: Drugs: OCS (prednisone/prednisolone)
Oral Corticosteroid (prednisone/prednisolone)
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With the Indicated Percent Reduction From Baseline in Oral Corticosteroid (OCS) Dose During Weeks 20 to 24 While Maintaining Asthma Control
Timepoint [1] 0 0
Baseline; Weeks 20 to 24
Secondary outcome [1] 0 0
Number of Participants Who Achieved a Reduction of >=50% in Their Daily Oral Corticosteroid (OCS) Dose Compared With Baseline Dose, During Weeks 20 to 24 While Maintaining Asthma Control
Timepoint [1] 0 0
Baseline; Weeks 20 to 24
Secondary outcome [2] 0 0
Number of Participants Who Achieved a Reduction of Their Daily OCS Dose to <=5.0 mg During Weeks 20 to 24 While Maintaining Asthma Control
Timepoint [2] 0 0
Weeks 20 to 24
Secondary outcome [3] 0 0
Number of Participants Who Achieved a Total Reduction of OCS Dose During Weeks 20 to 24 While Maintaining Asthma Control
Timepoint [3] 0 0
Weeks 20 to 24
Secondary outcome [4] 0 0
Median Percentage Change From Baseline in Daily OCS Dose During Weeks 20 to 24 While Maintaining Asthma Control
Timepoint [4] 0 0
Baseline; Weeks 20 to 24

Eligibility
Key inclusion criteria
- Informed Consent and Study Compliance: Subjects must be able to give written informed
consent prior to participation in the study, which will include the ability to comply
with the requirements and restrictions listed in the consent form.

- Systemic Corticosteroids: Requirement for regular treatment with maintenance systemic
corticosteroids in the 6 months prior to Visit 1 and using a stable oral
corticosteroid dose for 4 weeks prior to Visit 1. Subjects must be taking 5.0 to 35
mg/day of prednisone or equivalent at Visit 1 and must agree to switch to study
required prednisone/prednisolone as their oral corticosteroid and use it per protocol
for the duration of the study.

- Inhaled Corticosteroids: Requirement for regular treatment with high dose inhaled
corticosteroid in the 6 months prior to Visit 1. For 18 years of age and older:
inhaled corticosteroid (ICS) dose must be >=880 microgram (µg)/day fluticasone
propionate (FP) (ex-actuator) or equivalent daily. For ICS/ long acting beta2 agonist
(LABA) combination preparations, the highest approved maintenance dose in the local
country will meet this ICS criterion. For ages 12 to 17: ICS dose must be >=440 µg/day
FP (ex-actuator) or equivalent daily.

- Controller Medication: Current treatment with an additional controller medication for
at least 3 months OR documentation of having used and failed an additional controller
medication for at least 3 successive months during the prior 12 months [e.g., LABA,
leukotriene receptor antagonist (LTRA), or theophylline].

- Eosinophilic Asthma: Prior documentation of eosinophilic asthma or high likelihood of
eosinophilic asthma.

- FEV1: Persistent airflow obstruction as indicated by a pre-bronchodilator FEV1 <80%
predicted.

- Asthma: Evidence of asthma indicated by airway reversibility, hyperresponsiveness or
airway variability.
Minimum age
12 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Smoking history: Current smokers or former smokers with a smoking history of >=10 pack
years.

- Concurrent Respiratory Disease: Presence of a clinically important lung condition
other than asthma.

- Malignancy: A current malignancy or previous history of cancer in remission for less
than 12 months prior screening

- Liver Disease: Unstable liver disease

- Cardiovascular: Subjects who have severe or clinically significant cardiovascular
disease uncontrolled with standard treatment.

- Other Concurrent Medical Conditions: Subjects who have known, pre-existing, clinically
significant endocrine, autoimmune, metabolic, neurological, renal, gastrointestinal,
hepatic, haematological or any other system abnormalities that are uncontrolled with
standard treatment.

- Eosinophilic Diseases: Subjects with other conditions that could lead to elevated
eosinophils such as Hypereosiniophilic Syndromes, including Churg-Strauss Syndrome, or
Eosinophilic Esophaghitis. Subjects with a known, pre-existing parasitic infestation
within 6 months prior to Visit 1 are also to be excluded.

- ECG: ECG assessment QTcF >=450 milliseconds (msec) or QTcF >= 480 msec for subjects
with Bundle Branch Block.

- Immunodeficiency: A known immunodeficiency (e.g. human immunodeficiency virus - HIV),
other than that explained by the use of corticosteroids taken as therapy for asthma.

- Omalizumab Use: Subjects who have received omalizumab [Xolair] within 130 days of
Visit 1.

- Other Monoclonal Antibodies: Subjects who have received any monoclonal antibody (other
than Xolair) to treat inflammatory disease within 5 half-lives of Visit 1.

- Investigational Medications: Subjects who have received treatment with an
investigational drug within the past 30 days or five terminal phase half-lives of the
drug whichever is longer, prior to Visit 1 (this also includes investigational
formulations of marketed products).

- Hypersensitivity: Subjects with a known allergy or intolerance to a monoclonal
antibody or biologic.

- Pregnancy: Subjects who are pregnant or breastfeeding. Patients should not be enrolled
if they plan to become pregnant during the time of study participation.

- Alcohol/Substance Abuse: A history (or suspected history) of alcohol misuse or
substance abuse within 2 years prior to Visit 1.

- Adherence: Subjects who have known evidence of lack of adherence to controller
medications and/or ability to follow physician's recommendations.

- Previous participation: Subjects who have previously any study of mepolizumab and
received Investigational Product.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/10/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/12/2013
Sample size
Target
Accrual to date
Final
135
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC,WA
Recruitment hospital [1] 0 0
GSK Investigational Site - New Lambton
Recruitment hospital [2] 0 0
GSK Investigational Site - Bedford Park
Recruitment hospital [3] 0 0
GSK Investigational Site - Parkville
Recruitment hospital [4] 0 0
GSK Investigational Site - Nedlands
Recruitment postcode(s) [1] 0 0
2305 - New Lambton
Recruitment postcode(s) [2] 0 0
5042 - Bedford Park
Recruitment postcode(s) [3] 0 0
3050 - Parkville
Recruitment postcode(s) [4] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Minnesota
Country [5] 0 0
United States of America
State/province [5] 0 0
Missouri
Country [6] 0 0
United States of America
State/province [6] 0 0
Ohio
Country [7] 0 0
United States of America
State/province [7] 0 0
Pennsylvania
Country [8] 0 0
United States of America
State/province [8] 0 0
South Carolina
Country [9] 0 0
Canada
State/province [9] 0 0
Ontario
Country [10] 0 0
Canada
State/province [10] 0 0
Quebec
Country [11] 0 0
Czech Republic
State/province [11] 0 0
Brno
Country [12] 0 0
Czech Republic
State/province [12] 0 0
Olomouc
Country [13] 0 0
Czech Republic
State/province [13] 0 0
Praha 4
Country [14] 0 0
Czech Republic
State/province [14] 0 0
Praha 8
Country [15] 0 0
France
State/province [15] 0 0
Gières
Country [16] 0 0
France
State/province [16] 0 0
Montpellier cedex 5
Country [17] 0 0
France
State/province [17] 0 0
Nantes cedex 1
Country [18] 0 0
France
State/province [18] 0 0
Paris Cedex 18
Country [19] 0 0
France
State/province [19] 0 0
Strasbourg
Country [20] 0 0
Germany
State/province [20] 0 0
Bayern
Country [21] 0 0
Germany
State/province [21] 0 0
Brandenburg
Country [22] 0 0
Germany
State/province [22] 0 0
Hessen
Country [23] 0 0
Germany
State/province [23] 0 0
Niedersachsen
Country [24] 0 0
Germany
State/province [24] 0 0
Rheinland-Pfalz
Country [25] 0 0
Germany
State/province [25] 0 0
Schleswig-Holstein
Country [26] 0 0
Mexico
State/province [26] 0 0
Jalisco
Country [27] 0 0
Netherlands
State/province [27] 0 0
Amsterdam
Country [28] 0 0
Netherlands
State/province [28] 0 0
Leeuwarden
Country [29] 0 0
Netherlands
State/province [29] 0 0
Rotterdam
Country [30] 0 0
Poland
State/province [30] 0 0
Bialystok
Country [31] 0 0
Poland
State/province [31] 0 0
Krakow
Country [32] 0 0
Poland
State/province [32] 0 0
Lodz
Country [33] 0 0
United Kingdom
State/province [33] 0 0
Leicestershire
Country [34] 0 0
United Kingdom
State/province [34] 0 0
Liverpool
Country [35] 0 0
United Kingdom
State/province [35] 0 0
Newcastle upon Tyne
Country [36] 0 0
United Kingdom
State/province [36] 0 0
Southampton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a randomised, double-blind, placebo-controlled, parallel-group, multicenter study of
mepolizumab in comparison with placebo in reducing Oral Corticosteroid (OCS) use in subjects
with severe refractory asthma. The study consists of four phases, OCS Optimisation Phase
(Week -8 to Week 0), and the double-blind treatment period divided into an Induction Phase
(Week 0 to Week 4), OCS Reduction Phase (Week 5 upto Week 20) followed by Maintenance Phase
(Week 20 to Week 24). During the Optimisation Phase the investigator will adjust the OCS
(prednisone/prednisolone) dose according to the Optimisation titration schedule based on a
review of Asthma Control Questionnaire (ACQ)-5 score and exacerbation. In the Induction Phase
subjects will be randomized 1:1 (approximately 60 per arm) to receive either mepolizumab (100
mg) administered subcutaneously (SC) or placebo every 4 weeks in addition to their existing
maintenance asthma therapy with the lowest dose of OCS from Optimisation Phase. The Induction
Phase will allow sufficient time for those subjects randomised to the mepolizumab arm to
achieve a decrease in the eosinophilic inflammation prior to the reduction in OCS. During the
Reduction Phase, subjects will continue receiving 100 mg mepolizumab/placebo every 4 weeks
and the OCS dose reduction will be done every 4 weeks using the reduction titration schedule
based on a review of eDiary parameters recorded by the subject, the subjects' exacerbation
history, and a review of the signs and symptoms of adrenal insufficiency. In the Maintenance
Phase subjects will be maintained without any further OCS dose adjustment. Subjects who
complete the 24 week double-blind period and meet the eligibility criteria, will be offered
the opportunity to participate in an open label extension (OLE) study otherwise they will
return for a Follow-up Visit 12 weeks after their last dose of double blind study treatment.
At each clinic visit, adverse events, safety labs, spirometery parameters and exacerbations
will be assessed. The pharmacokinetic samples will be collected in the beginning of the
treatment, prior to last dose, at the end of study (exit visit) and the follow up.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01691508
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01691508