A study of mepolizumab (study medicine) as an add-on therapy in subjects with severe uncontrolled asthma

• Register: EUCTR
• Last refreshed on: 8 August 2016
• Main ID: EUCTR2014-002513-27-NL
• Date of registration: 05/11/2014
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline Research & Development Ltd
• Public title: A study of mepolizumab (study medicine) as an add-on therapy in subjects with severe uncontrolled asthma
• Scientific title: A randomised, double-blind, placebo-controlled, parallel-group, multi-centre 24-week study to evaluate the efficacy and safety of mepolizumab adjunctive therapy in subjects with severe eosinophilic asthma on markers of asthma control
• Date of first enrolment: 22/12/2014
• Target sample size: 544
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-002513-27
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Belgium, Canada, Czech Republic, Estonia, Germany, Greece, Italy, Netherlands, Russian Federation, Slovakia, Spain, Ukraine, United States

Contacts

• Name: Clinical Trials Helpdesk
• Affiliation: GlaxoSmithKline Research & Development Ltd

• Name: Clinical Trials Helpdesk
• Affiliation: GlaxoSmithKline Research & Development Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
A subject will be eligible for inclusion in the study only if all of the following criteria
apply:
1. Age: At least 12 years of age at the time of signing the informed consent/assent.
[For those countries where local regulations permit enrolment of adults only, subject recruitment will be restricted to those who are = 18 years of age]
2. Inhaled Corticosteroid: A well-documented requirement for regular treatment with high dose inhaled corticosteroid (ICS) in the 12 months prior to Visit 1 with or without maintenance oral corticosteroids (OCS).
For subjects = 18 years old:
- ICS dose must be =880 mcg/day fluticasone propionate (FP) (exactuator) or equivalent daily.
- For ICS/LABA combination preparations, the highest approved
maintenance dose in the local country will meet this ICS criterion.
For subjects = 12 to = 17 years old:
- ICS dose must be =440 µg/day 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.
3. Controller Medication: Current treatment with an additional controller medication, besides ICS, for at least 3 months or a documented failure in the past 12 months of an additional controller medication for at least 3 successive months. [e.g., long-acting beta-2-agonist (LABA), leukotriene receptor antagonist (LTRA), or theophylline.]
4. Eosinophilic asthma: Prior documentation of eosinophilic asthma or high likelihood of eosinophilic asthma as per Randomisation Criteria 1 and 2 (see Section 5.3 of study protocol).
5. FEV1: Persistent airflow obstruction as indicated by :
- For subjects = 18 years of age at visit 1, a pre-bronchodilator FEV1 <80% predicted (NHANES III) recorded at Visit 1
- For subjects 12-17 years of age at Visit 1:
- A pre-bronchodilator FEV1 <90% predicted (NHANES III) recorded
at Visit 1 OR
- FEV1:FVC ratio < 0.8 recorded at Visit 1
6. Exacerbation history: Previously confirmed history of two or more
exacerbations requiring treatment with systemic CS (intramuscular (IM), intravenous, or oral), in the 12 months prior to visit 1, despite the use of high-dose ICS. For subjects receiving maintenance CS, the CS treatment for the exacerbations must have been a two-fold dose increase or greater.
7. Gender: Male or Eligible Female - To be eligible for entry into the study, females of childbearing potential must commit to consistent and correct use of an acceptable method of birth control (Refer to Appendix 5 of study Protocol) for the duration of the trial and for 4 months after the last study drug administration.
8. Informed Consent/Assent: Able to give written informed consent/assent prior to participation in the core study, which will include the ability to comply with the requirements and restrictions listed in the consent/assent form and in this protocol.
Subjects must be able to read, comprehend, and write at a level sufficient to complete study related materials.
Written informed consent must be obtained from ALL patients/legally authorized representative(s); for patients 12-17 years old, written informed assent must be obtained in addition to the legally authorized representative(s)’ consent.
French subjects: 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.
Inclusion Criteria for the Physical Activity Sub-Study and Physical Activity Sub-Study:
A subject will be eli
Exclusion criteria:
A subject will not be eligible for inclusion in the study if any of the following criteria apply:
1. Smoking history: 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). 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 known pre-existing, 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.
3. Malignancy: A current malignancy or previous history of cancer in remission for less than 12 months prior to screening (Subjects that had localized carcinoma of the skin which was resected for cure will not be excluded).
4. Liver Disease: Known, pre-existing, 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. Including but not limited to:
a. known ejection fraction of <30% OR
b. severe heart failure meeting New York Heart Association Class IV (see Appendix 8 of study Protocol) classification OR
c. hospitalised in the 12 months prior to Visit 1 for severe heart failure meeting New York Heart Association Class III (see Appendix 8 of study Protocol) OR
d. angina diagnosed less than 3 months prior to Visit 1 or at Visit 1
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 Hypereosinophilic Syndromes, including Churg-Strauss Syndrome (Eosinophilic Granulomatosis with Polyangiitis; EGPA), or Eosinophilic Esophagitis. Subjects with a known, pre-existing parasitic infestation within 6 months prior to Visit 1 are also to be excluded.
8. ECG Assessment:
QTc(F) =450msec or QTc(F) =480 msec for subjects with Bundle Branch Block at Visit 1.
9. Alcohol/Substance Abuse: A history (or suspected history) of alcohol misuse or substance abuse within 2 years prior to Visit 1.
10. Immunodeficiency: A known immunodeficiency (e.g. human immunodeficiency virus – HIV), other than that explained by the use of corticosteroids taken as therapy for asthma.
11. Xolair: Subjects who have received omalizumab (Xolair) within 130 days of Visit 1.
12. Other Monoclonal Antibodies: Subjects who have received any monoclonal antibody (other than Xolair) to treat inflammatory disease within 5 half-lives of Visit 1.
13. 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).
14. Hypersensitivity: Subjects with allergy/intolerance to a mon

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Subjects with severe asthma
MedDRA version: 17.1 Level: PT Classification code 10003553 Term: Asthma System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Intervention(s)

Product Name: Mepolizumab
Product Code: SB-240563
Pharmaceutical Form: Lyophilisate for solution for injection
INN or Proposed INN: Mepolizumab
CAS Number: 196078-29-2
Current Sponsor code: SB240563
Other descriptive name: MEPOLIZUMAB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Primary end point(s): ? Mean change from baseline in St. George’s Respiratory Questionnaire
(SGRQ) score at Week 24

Timepoint(s) of evaluation of this end point: Week 24

Secondary Objective: ? To assess the effects of mepolizumab compared to placebo on lung function.
? To assess the effects of mepolizumab compared to placebo on HR-QoL.
? To assess the effects of mepolizumab compared to placebo on asthma control.

Main Objective: ? To evaluate the efficacy of mepolizumab 100 mg subcutaneous (SC) every 4 weeks versus placebo on health-related quality of life (HR-QoL) in adult and adolescent subjects with severe eosinophilic asthma.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Week 24

Secondary end point(s): ? Mean change from baseline in clinic prebronchodilator FEV1 at Week 24
? Percentage of subjects achieving a 4 point or greater reduction from baseline in SGRQ score at Week 24
? Mean change from baseline in Asthma Control Questionnaire (ACQ-5) score at Week 24

Secondary ID(s)

200862

2014-002513-27-IT

Source(s) of Monetary Support

GlaxoSmithKline Research & Development Ltd