Clinical Trials Register

Summary
EudraCT Number:	2007-000838-39
Sponsor's Protocol Code Number:	MHE104317
National Competent Authority:	Norway - NOMA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2010-03-30
Trial 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

Norway - NOMA

A.2

EudraCT number

2007-000838-39

A.3

Full title of the trial

Expanded access program for mepolizumab in subjects with HES

A.3.1

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

Expanded access program for mepolizumab in subjects with HES

A.4.1

Sponsor's protocol code number

MHE104317

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	GlaxoSmithKline Research & 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	GlaxoSmithKline Research & Development Ltd
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 Research & Development Ltd
B.5.2	Functional name of contact point	GSK Clinical Support Help Desk
B.5.3	Address:
B.5.3.1	Street Address	1-3 Iron Bridge Road, Stockley Park West
B.5.3.2	Town/ city	Uxbridge, Middlesex
B.5.3.3	Post code	UB11 - 1BT
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+440800 783 9733
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	Yes
D.2.1.1.1	Trade name	Nucala
D.2.1.1.2	Name of the Marketing Authorisation holder	GlaxoSmithKline Trading Services Limited
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/04/213
D.3 Description of the IMP
D.3.1	Product name	Nucala
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	Intravenous drip use (Noncurrent) 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.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
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	Yes
D.3.11.13.1	Other medicinal product type	Mepolizumab (SB-240563) is a fully humanised IgG antibody (IgG1, kappa) with human heavy and light chain frameworks.

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Subjects with life-threatening HES

E.1.1.1

Medical condition in easily understood language

Subjects with HES

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	20.0
E.1.2	Level	PT
E.1.2	Classification code	10048643
E.1.2	Term	Hypereosinophilic syndrome
E.1.2	System Organ Class	10005329 - Blood and lymphatic system disorders

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

Safety:
To assess the long-term AE profile
associated with mepolizumab therapy.

Efficacy:
To characterize individual dosing
requirements for control of disease.

E.2.2

Secondary objectives of the trial

Not Applicable

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. In accordance with local procedures, written informed consent/assent can be obtained from the subject or legally authorized representative
2. ≥ 12 years of age at the time of signing the informed consent/assent
3. Meets the diagnostic criteria for HES as defined by:
- Eosinophilia >1500 cells/μl for at least 6 months with evidence of symptoms and
signs of organ system involvement or dysfunction that can be directly related to
eosinophilia (with no evidence of parasitic, allergic or other recognised causes of
eosinophilia such as connective tissues disease, malignancy)
or
- Eosinophilia of >1500 cells/μl for less than 6 months and meet the other criteria
for HES accompanied by clear evidence of eosinophil tissue infiltration and with
exclusion of secondary causes of eosinophilia as above.

4. Subjects meeting all three of the following criteria will be eligible:
- The indication, HES, is a seriously debilitating or life-threatening disease;
- There is no satisfactory alternative treatment: documented failure (lack of
efficacy or a contra-indication) to at least 3 standard therapies (corticosteroids,
cytotoxic agents, immunomodulatory therapy, and Imatinib mesylate) at the
appropriate duration and dose or demonstrated clinical benefit from prior
treatment with mepolizumab; and
- There is reason to believe that the benefit:risk ratio for mepolizumab in the
indication is positive.

E.4

Principal exclusion criteria

1. Subjects without HES but with other conditions associated with eosinophilic
pathological processes such as Eosinophilic Granulomatosis with Polyangiitis
[EGPA], Wegener’s Granulomatosis, atopic disorders, parasitic infections,
eosinophilic gastroenteropathies.
2. Female subjects of childbearing potential who are not using a highly effective
method of contraception:
Consistent and correct use of an acceptable method of birth control for one month
prior to the start of the investigational product and until 16 weeks after the last
dose (see Section 12.2 of the protocol for a list of acceptable methods of contraception).
3. Pregnant or lactating females
4. Subjects with severe/life-threatening underlying disease unrelated to HES where life
expectancy is estimated to be less than 3 months
5. Subjects with a history of or current malignancy:
- Subjects with a history of or current lymphoma
- Subjects with current malignancy or previous history of cancer in remission for
less than 12 months prior to the first dose. Subjects that had localized carcinoma (i.e., basal or squamous cell) of the skin which was resected for cure will not be excluded.
6. Subjects with history of serious allergic reaction (hypersensitivity/anaphylaxis) to
anti-IL5 or other antibody therapy or known or suspected hypersensitivity to any component of mepolizumab, leading to treatment discontinuation
7. Subjects with current drug or alcohol abuse where uncertain compliance with the
protocol and/or with the medical management instruction of the investigator may cause safety risk.

8. Subjects who have received treatment with an investigational agent (biologic or nonbiologic,
excluding mepolizumab) within the past 30 days or 5 drug half-lives
whichever is longer, prior to the administration of mepolizumab under this protocol.The term “investigational” applies to any drug not approved for sale in the country in which it is being used or investigational formulations of marketed products.

E.5 End points

E.5.1

Primary end point(s)

Serious AEs (SAEs).
Non-serious AEs related to mepolizumab as
assessed by the investigator

E.5.1.1

Timepoint(s) of evaluation of this end point

Each clinic visit

E.5.2

Secondary end point(s)

-Mean 28-day SC dose (mg) for the last
3 administrations

E.5.2.1

Timepoint(s) of evaluation of this end point

Each clinic visit

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

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Compassionate Use

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

Yes

E.7.1.3.1

Other trial type description

Compassionate use study

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

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

E.8.2.3

Other

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.8.4.1

Number of sites anticipated in Member State concerned

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

Information not present in EudraCT

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

E.8.7

Trial has a data monitoring committee

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

End of trial is specified when last subject last patient has been reached.

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

Number of subjects for this age range:

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:

200

F.1.3

Elderly (>=65 years)

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

Yes

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

Yes

F.3.3.7.1

Details of other specific vulnerable populations

Adolescents sign assent form, the parent/guardian signs ICF prior to entry to study.

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

100

F.4.2.2

In the whole clinical trial

200

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)

Other treatments that are appropriate for managing the subject's condition.

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

2010-05-04

Ethics Committee Opinion of the trial application

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

P. End of Trial
P.	End of Trial Status	Completed

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