severe eosinophilic asthma MedDRA version: 18.1 Level: LLT Classification code 10068462 Term: Eosinophilic asthma System Organ Class: 100000004855
Conditions
Interventions
Product Name: Mepolizumab
Product Code: SB-240563
Pharmaceutical Form: Lyophilisate for solution for injection
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the
Sponsors
University medical center of Johannes Gutenberg University Mainz
Eligibility
Sex/Gender
All
Inclusion criteria
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 =65 years) yes F.1.3.1 Number of subjects for this age range 18
Exclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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;Secondary Objective: 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 ;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;Timepoint(s) of evaluation of this end point: week 24 time of response | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 1 month 3 month 6 month 9 month 12 month;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 ov | — |
Countries
Germany
Contacts
Public ContactStephanie Korn
University Medical Center of the Johannes Gutenberg University Mainz
Outcome results
None listed