Clinical Trials Register

Summary
EudraCT Number:	2015-001868-19
Sponsor's Protocol Code Number:	2015-001
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2015-07-06
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

Germany - PEI

A.2

EudraCT number

2015-001868-19

A.3

Full title of the trial

A randomized, double-blind, placebo-controlled, mono-center study to evaluate the effects of mepolizumab on airway physiology in patients with eosinophilic asthma: the MEMORY study

Eine randomisierte, doppel-blinde, Placebo-kontrollierte monozentrische Studie zur Bewertung der Effekte von Mepolizumab auf die Atemwegsphysiologie bei Patienten mit eosinophilem Asthma: die MEMORY-Studie

A.3.1

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

Effects of mepolizumab compared to placebo on airway physiology in patients with eosinophilic asthma: MEMORY study

Effekte von Mepolizumab im Vergleich zu Placebo auf die Atemwegsphysiologie bei Patienten mit eosinophilem Asthma: die MEMORY-Studie

A.3.2

Name or abbreviated title of the trial where available

MEMORY

A.4.1

Sponsor's protocol code number

2015-001

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	University medical center of Johannes Gutenberg University Mainz
B.1.3.4	Country	Germany
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	GlaxoSmithKline
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	University Medical Center of the Johannes Gutenberg University Mainz
B.5.2	Functional name of contact point	Stephanie Korn
B.5.3	Address:
B.5.3.1	Street Address	Langenbeckstrasse 1
B.5.3.2	Town/ city	Mainz
B.5.3.3	Post code	D-55131
B.5.3.4	Country	Germany
B.5.4	Telephone number	00496131175785
B.5.5	Fax number	00496131175661
B.5.6	E-mail	Stephanie.Korn@unimedizin-mainz.de

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.3.11 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)	Yes
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 eosinophilic asthma

schweres eosinophiles Asthma

E.1.1.1

Medical condition in easily understood language

severe eosinophilic asthma

schweres eosinophiles 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	18.1
E.1.2	Level	LLT
E.1.2	Classification code	10068462
E.1.2	Term	Eosinophilic asthma
E.1.2	System Organ Class	100000004855

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of the trial is to investigate the effects of mepolizumab compared with placebo on parameters of airway physiology including bodyplethysmography and CO diffusion capacity

E.2.2

Secondary objectives of the trial

The secondary objectives of the trial are
• effects of mepolizumab compared with placebo on exercise tolerance in a subgroup of patients
• time to clinical response
• time to change of baseline parameters of clinical response
• effects of mepolizumab compared with placebo on clinical parameters of asthma control, including ACQ, AQLQ, SGRQ, BDI/TDI and fatigue
• baseline asthma parameters as potential predictors of clinical response

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Patients meeting all of the following criteria will be considered for admission to the trial:
1. Patients 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.
2. Male or female patients at least 18 years of age at date of informed consent
3. Females of childbearing potential must commit to consistent and correct use of an acceptable method of birth control. Female patients must be postmenopausal (for at least 12 months without an alternative medical cause), surgically sterile, or if sexually active, be practicing an effective method of birth control throughout the study. Reliable highly effective contraceptions with low failure rate are systemic contraceptives (oral, implants, injection), intrauterine device (IUD) and intrauterine hormone-releasing system (IUS).
A urine pregnancy test is required of all female patients. This test will be performed at the initial screening visit (visit 1). In addition, a urine pregnancy test will be performed prior to randomization and at each scheduled study visit prior to the injection of the investigational product and at the follow-up visit.
4.Physician-diagnosis of asthma and evidence of asthma as documented by reversibility of airflow obstruction (FEV1 12% or 200 ml) demonstrated at visit 1 or visit 2 or documented in the previous 24 month.
5. Inhaled corticosteroid (ICS) dose must be ≥ 1000 μg/day beclomethasone (BDP) or equivalent daily with or without maintenance oral corticosteroids.
6. Treatment in the past 12 months with an additional controller medication for at least 3 successive months, e.g., long-acting beta-2-agonist (LABA), leukotriene receptor antagonist (LTRA), or theophylline.
7. Persistent airflow obstruction as indicated by a pre-bronchodilator FEV1 < 80% predicted recorded at Visit 1 or < 90% for patients on oral corticosteroids.
8. An elevated peripheral blood eosinophil level of  300/L that is related to asthma or 150/L in patients treated with oral corticosteroids as maintenance therapy demonstrated at visit 1 or in the previous 12 months
9. Confirmed history of two or more exacerbations requiring treatment with systemic corticosteroids (intramuscular, intravenous, or oral), in the 12 months prior to visit 1, despite the use of high-dose inhaled corticosteroids. For patients receiving maintenance corticosteroids, the corticosteroid treatment for the exacerbations must have been a two-fold increase or greater in the dose.
10. Patients must be able to read, comprehend, and write at a level sufficient to complete study related materials

E.4

Principal exclusion criteria

Patients presenting with any of the following criteria will not be included in the trial:
1. Current smokers or former smokers with a smoking history of 10 pack years (number of pack years = (number of cigarettes per day / 20) x number of years smoked). Patients who have not smoked for ≥ 6 months before visit 1 and have < 10 pack years can be included into the study.
2. Presence of a clinically important lung condition other than asthma. This includes 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. Patients who experience an infection or exacerbation between screening and randomization can be re-screened four weeks after recovery of the infection or exacerbation with keeping it´s original screening number. The data of the re-screening visit should be documented in the eCRF.
3. Evidence of clinically significant abnormality in the haematological (except eosinophil level), biochemical or urinalysis screen at Visit 1, as judged by the investigator. Abnormalities based on known underlying diseases are not excluded.
4. Evidence of significant abnormality in the 12 lead ECG at Visit 1.
5. A current malignancy or previous history of cancer in remission for less than five years prior to screening (Patients that had localized carcinoma of the skin which was resected for cure will not be excluded).
6. Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices or persistent jaundice), cirrhosis, and known biliary abnormalities (with the exception of Gilbert’s syndrome or asymptomatic gallstones).
7. Patients who have received omalizumab [Xolair] within 130 days of Visit 1.
8. Patients who have received any biological to treat inflammatory disease within 5 half-lives of visit 1
9. Patients who have received methotrexate, troleandomycin, cyclosporin, azathioprine within 90 days of visit 1
10. Patients with allergy/intolerance to the excipients in the mepolizumab formulation.
11. Ongoing participation in other clinical trials or 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).
12. Patients who are pregnant or breastfeeding. Patients should not be enrolled if they plan to become pregnant during the time of study participation.
13. Patients who have clinically significant cardiovascular, endocrine, autoimmune, metabolic, neurological, renal, gastrointestinal, hepatic, hematological or any other system abnormalities that are uncontrolled with standard treatment.
14. A history (or suspected history) of alcohol misuse or substance abuse within 2 years prior to Visit 1.
15. A parasitic infestation within 6 months prior to Visit 1.
16. Patients who are not able or willing to comply with the provisions of controller medication and/or to follow trial physician’s recommendations.
17. Patients, who are legally institutionalized.

E.5 End points

E.5.1

Primary end point(s)

The primary outcome is the mean change from baseline in pre- and post-bronchodilator forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), residual volume (RV), total lung capacity (TLC), airway resistance, inspiratory capacity (IC), and CO diffusion capacity at visit 10 (week 24) and at time of response

E.5.1.1

Timepoint(s) of evaluation of this end point

week 24
time of response

E.5.2

Secondary end point(s)

• Mean change from baseline in pre- and post-bronchodilator forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), residual volume, total lung capacity, airway resistance, inspiratory capacity, and CO diffusion capacity over the 48-week treatment period at prespecified timepoints (1, 3, 6, 9 and 12 months)
• Exercise tolerance in a subgroup of patients
o Mean change from baseline in exercise endurance time during a sub-maximal constant-load cycle ergometry test after 1, 3, 6, 9 and 12 months of treatment.
o Mean change from baseline in inspiratory capacity (IC) at rest and at peak during sub-maximal constant-load cycle ergometry test after 1, 3, 6, 9 and 12 months of treatment.
o Mean change from baseline in exertional dyspnea and leg discomfort (Borg CR10 Scale®) during sub-maximal constant-load cycle ergometry test after 1, 3, 6, 9 and 12 months of treatment
• Time to clinical response and time to change of baseline parameters of clinical response (sense of smell and taste, lung volumes, CO diffusion capacity, FEV1 reversibility, exhaled NO (eNO), blood eosinophils, eosinophilic cationic protein (ECP), blood periostin).
• Mean change from baseline in clinical parameters of asthma control, including ACQ, AQLQ, SQRG, BDI/TDI and fatigue.
• Mean change from baseline in number of days off school/work over the 48-week treatment period
• Time to first clinically significant exacerbation requiring oral or systemic corticosteroids, hospitalization, and/or emergency department (ED) visits
• Frequency of clinically significant exacerbations
• Time to first exacerbation requiring hospitalization or emergency department (ED) visit
• Frequency of exacerbations requiring hospitalization (including intubation and admittance to an intensive care unit (ICU)) or ED visits
• GETE rating by physician and patient at time of response and over the 52-week treatment period at pre-specified timepoints (1, 3, 6, 9 and 12 months)
• Mean change in proportion of patients with nasal polyps, chronic sinusitis and loss of smell and taste
• Time to premature discontinuation

Exploratory Efficacy Endpoints
• Clinical response to mepolizumab in relation to asthma parameters which potentially predict clinical response (age at onset and duration of asthma, prior asthma medication, presence of nasal polyps, sense of smell and taste, allergic sensitization (skin prick test, total and specific IgE against aeroallergens and Staph. aureus enterotoxin), reversibility of airflow obstruction, eNO, blood eosinophils, eosinophilic cationic protein (ECP), blood periostin, ANA, ANCA, ECP

Safety Endpoints
• Routine safety assessments are incorporated throughout and/or at the end of treatment period including AE and SAE reporting, withdrawals, pregnancy, hematological and clinical chemistry parameters, ECG and vital signs (pulse rate and systolic and diastolic blood pressure).

E.5.2.1

Timepoint(s) of evaluation of this end point

1 month
3 month
6 month
9 month
12 month

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

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

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

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

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

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 the trial is LVLS

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

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

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)

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.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)

After the end of the treatment the study drug will be discontinued. After end of the trial the patients will be treated according to current guidelines. After the end of the study all patients can be treated with mepolizumab, if this medication is by then licensed by the approval authority.

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

2015-10-15

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-07-31

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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