Clinical Trials Register

Summary
EudraCT Number:	2012-001497-29
Sponsor's Protocol Code Number:	MEA115575
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-07-12
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2012-001497-29

A.3

Full title of the trial

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

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A study of mepolizumab (study medication) as add-on therapy in subjects who require daily oral corticosteroids to treat their severe asthma

A.4.1

Sponsor's protocol code number

MEA115575

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/219/2011

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	GlaxoSmithKline Research and Development Ltd
B.1.3.4	Country	United Kingdom
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	GSK
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	GlaxoSmithKline
B.5.2	Functional name of contact point	Clinical Trials Helpdesk
B.5.3	Address:
B.5.3.1	Street Address	Iron Bridge Road
B.5.3.2	Town/ city	Uxbridge
B.5.3.3	Post code	UB11 1BU
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+44 02089904466
B.5.5	Fax number	+4402089901234
B.5.6	E-mail	GSKClinicalSupportHD@gsk.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Mepolizumab
D.3.2	Product code	SB-240563
D.3.4	Pharmaceutical form	Lyophilisate for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	MEPOLIZUMAB
D.3.9.1	CAS number	196078-29-2
D.3.9.2	Current sponsor code	SB-240563
D.3.9.3	Other descriptive name	MEPOLIZUMAB
D.3.9.4	EV Substance Code	SUB21650
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	250
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for injection
D.8.4	Route of administration of the placebo	Subcutaneous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Severe asthma

E.1.1.1

Medical condition in easily understood language

Severe asthma

E.1.1.2

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	PT
E.1.2	Classification code	10003553
E.1.2	Term	Asthma
E.1.2	System Organ Class	10038738 - Respiratory, thoracic and mediastinal disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To compare the effects of mepolizumab adjunctive therapy with placebo on reducing the use of maintenance oral corticosteroids (OCS) in systemic corticosteroid dependent subjects with severe refractory asthma with elevated eosinophils.

E.2.2

Secondary objectives of the trial

To compare the efficacy, safety, and tolerability of mepolizumab compared with placebo, in subjects with severe refractory asthma with elevated eosinophils including an evaluation of the effects of mepolizumab on markers of asthma impairment and risk
including, asthma symptoms, pulmonary function, exacerbation rate and quality of life as assessed by the St. George’s Respiratory Questionnaire.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

A sub-study will be conducted only at sites in Canada. The objective of this sub-study is to assess 1) eosinophil progenitor cells in blood and sputum samples at baseline and 2) to study the effect of anti-IL-5 treatment on these progenitor cells levels in sputum and blood. Refer to Section 11.7 in the protocol for further details.

E.3

Principal inclusion criteria

Subjects eligible for enrolment in the study must meet all of the following criteria:
1. 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 equirements and restrictions listed in the consent form. Subjects must be able to read, comprehend, and write at a level sufficient to complete study related materials.
2. Age: At least 12 years of age at Visit 1 and a minimum weight of 45kg [For those countries where local regulations permit enrolment of adults only, subject recruitment will be restricted to those who are >18 years of age]
3. Systemic Corticosteroids: Subjects with severe asthma and a well-documented 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 – 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.
4. Inhaled Corticosteroids: A documented requirement for regular treatment with high dose inhaled corticosteroid in the 6 months prior to Visit 1.
• For 18 years of age and older:
• ICS dose must be ≥880 mcg/day fluticasone propionate (FP) (ex-actuator) or equivalent daily.
• For ICS/LABA combination preparations, the highest approved maintenance dose in the local country will meet this ICS criterion.
• For ages 12-17
• ICS dose must be ≥440 μg/day fluticasone propionate (FP) (ex-actuator) or equivalent daily.
• For ICS/LABA combination preparations, the mid-strength approved maintenance dose in the local country will meet this ICS criterion.
5. 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., long-acting beta2-agonist (LABA), leukotriene receptor antagonist (LTRA), or theophylline].
6. Eosinophilic asthma: Prior documentation of eosinophilic asthma or high likelihood of eosinophilic asthma as per Randomisation Criteria 1 and 2.
7. Gender: Male or Eligible Female
To be eligible for entry into the study, 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 trial and for 4 months after the last study drug administration.
Subjects in France: 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.

E.4

Principal exclusion criteria

Subjects meeting any of the following criteria must not be enrolled in the study:
1. Smoking history: Current smokers or former smokers with a smoking history of ≥10 pack years. A former smoker is defined as a subject who quit smoking at least 6 months prior to Visit 1.
2. Concurrent Respiratory Disease: Presence of a clinically important lung condition other than asthma. This includes but is not limited to current infection, bronchiectasis, pulmonary fibrosis, bronchopulmonary aspergillosis, or diagnoses of emphysema or chronic bronchitis (chronic obstructive pulmonary disease other than asthma) or a history of lung cancer.
3. Malignancy: A current malignancy or previous history of cancer in remission for less than 12 months prior screening (Subjects that had localized carcinoma (ie, basal or squamous cell) of the skin which was resected for cure will not be excluded).
4. Liver Disease: Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, esophageal or gastric varices or persistent jaundice), cirrhosis, and known biliary abnormalities (with the exception of Gilbert’s syndrome or asymptomatic gallstones).
5. Cardiovascular: Subjects who have severe or clinically significant cardiovascular disease uncontrolled with standard treatment.
6. 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.
7. 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.
8. ECG: ECG assessment QTcF ≥ 450msec or QTcF ≥ 480 msec for subjects with Bundle Branch Block.
9. Immunodeficiency: A known immunodeficiency (e.g. human immunodeficiency virus – HIV), other than that explained by the use of corticosteroids taken as therapy for asthma.
10. Omalizumab Use: Subjects who have received omalizumab [Xolair] within 130 days of Visit 1.
11. Other Biologics: Subjects who have received any biological (other than Xolair) to treat inflammatory disease within 5 half-lives of Visit 1 12. 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).
13. Hypersensitivity: Subjects with a known allergy or intolerance to a monoclonal antibody or biologic.
14. Pregnancy: Subjects who are pregnant or breastfeeding. Patients should not be enrolled if they plan to become pregnant during the time of study participation.
15. Alcohol/Substance Abuse: A history (or suspected history) of alcohol misuse or substance abuse within 2 years prior to Visit 1.
16. Adherence: Subjects who have known evidence of lack of adherence to controller medications and/or ability to follow physician’s recommendations.
17. Previous participation: Subjects who have previously any study of mepolizumab and received Investigational Product.
Re-screening of subjects will be allowed only upon approval by the medical monitor.

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint is the percent reduction of oral corticosteroid (OCS) dose at week 24 compared to the baseline dose.

E.5.1.1

Timepoint(s) of evaluation of this end point

One timepoint, Week 24

E.5.2

Secondary end point(s)

• The proportion of subjects who achieve a reduction of 50% or greater in their daily OCS dose, compared to baseline dose, during weeks 20-24 while maintaining asthma control.
• The proportion of subjects who achieve a reduction of OCS dose to less than or equal to 5.0mg, while maintaining asthma control during weeks 20 – 24
• The proportion of subjects who achieve a total reduction of OCS dose while maintaining asthma control during weeks 20 - 24
• Median percentage reduction from baseline in daily OCS dose at week 24
• Proportion of eligible subject who achieve complete reduction of OCS
• Annualised rate of clinically significant exacerbations
• Annualised rate of exacerbations requiring hospitalization
• Annualised rate of exacerbations requiring hospitalization or ED visits
• Mean change from baseline in St. George’s Respiratory Questionnaire at week 24
• Mean change from baseline in clinic pre-bronchodilator FEV1 at week 24

E.5.2.1

Timepoint(s) of evaluation of this end point

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

Yes

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

Canada

Mexico

United States

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

Last Subject Last Visit

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

120

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

The investigator is responsible for ensuring that consideration has been given to the poststudy
care of the patient’s medical condition whether or not GSK is providing specific
post study treatment. Subjects who complete 24 weeks treatment period, and return for the Exit Visit at week 24, may be recruited into a continuation protocol with open-label mepolizumab. However subjects may be prescribed appropriate alternative asthma therapy if needed and as determined by the study Investigator.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2012-08-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-09-13

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2013-12-12

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