E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Severe persistent allergic asthma |
|
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate persistency in treatment responder classification between assessments at 16 and 32 weeks after starting omalizumab therapy given as add on to optimized asthma therapy in patients who remain uncontrolled despite GINA step 4 therapy. Treatment response is defined by at least marked improvement of overall asthma control as assessed by physician global evaluation of treatment effectiveness. |
|
E.2.2 | Secondary objectives of the trial |
To evaluate persistency in treatment responder classification between assessments at 16 and 32 weeks after randomization to optimized asthma therapy alone in patients who remain uncontrolled despite GINA step 4 therapy.
To evaluate the effect of omalizumab as add-on to optimized asthma therapy compared to optimized asthma therapy alone : Global Evaluation of Treatment Effectiveness and FEV1 at weeks 16 and 32, rate of clinically significant exacerbations, Asthma Control Questionnaire and meaningful nighttime awakenings at week 16 and 32, rate of hospitalizations (...) for clinically significant and severe asthma exacerbations, reduction of oral corticosteroids dose in patients requiring OCS as maintenance therapy, Quality of life, Work Productivity, Activity Impairment.
Exploratory : Evaluation of response rate to omalizumab treatment compared to previous double blind trial, Fractional Exhaled Nitric Oxide as non-invasive measure of airway inflammation in a subgroup of patients |
|
E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
- males or females of any race who are 12-75 years of age - body weight 20 to 150 kg and total serum IgE level 30 to 700 IU/ml - diagnosis of allergic asthma ≥1 year duration according to ATS criteria and at screening a history consistent with GINA step 3 or 4 clinical features - positive skin prick test to at least one perennial allergen documented within the past 2 years or taken at Visit 1. Patients with a total IgE level of ≤ 76 IU require an unequivocal positive RAST test to be eligible - demonstrating at least 12% increase in FEV1 within 30 minutes of taking salbutamol - FEV1 between 40 and 80% of the predicted normal value for the patient at screening and randomization - receiving high dose inhaled corticosteroid ≥ 800μg BDP or equivalent and a regular inhaled long acting beta-2 agonist for at least 3 months prior to screening and > 1000 µg BDP and a LABA for at least 4 weeks during the run-in and at randomization - who have suffered at least two independent documented severe asthma exacerbations while receiving high doses of ICS (≥ 800 µg BDP or equivalent) plus regular inhaled LABA requiring treatment with systemic (oral or IV) corticosteroids. Qualifying exacerbations must have taken place in the 3 years prior to screening, and at least one severe exacerbation must have occurred within the previous 12 months - with evidence of poor asthma control at screening and for at least 4 weeks immediately prior to randomization |
|
E.4 | Principal exclusion criteria |
- pregnant or nursing women, and women of childbearing potential unless they meet the definition of post-menopausal or use one or more acceptable methods of contraception Patients : - who, for reasons other than asthma, have received systemic corticosteroids within 4 weeks of Visit 1 or are likely to require it during the study for reasons other than asthma - not adhering to the antihistamine washout prior to the skin prick tests at Visit 1 - taking ß adrenergic antagonist medication or anticipate use during the study - taking methotrexate, gold salts, cyclosporin or troleandomycin within 3 months of Visit 11 (or anticipated their use during the study) - currently receiving desensitization therapy with less than 3 months of stable maintenance doses prior to the screening visit (Visit 1) - foreseen to require additional asthma medication during the last 4 weeks of the run-in period - being treated for an asthma exacerbation during the 4 weeks immediately prior to randomization - with a smoking history > 10 pack years or an active lung disease other than allergic asthma, e.g. COPD - with elevated serum IgE levels for reasons other than allergy - with significant underlying medical conditions that could impact interpretation of results should be excluded (e.g.: infection, hematological disease, malignancy, renal, hepatic, coronary heart disease or other cardiovascular disease, endocrinologic or gastrointestinal disease) within the previous 3 months - who have previously been randomized into this or any other omalizumab study or who have received omalizumab (prescribed)
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary variable, persistency rate (%) of response, is based on the investigator’s global evaluation of treatment effectiveness, dichotomized to responders (excellent or good) and non-responders (moderate, poor or worsening) for patients receiving omalizumab as add on to optimal asthma therapy, assessed at week 16 and week 32. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
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.8.6 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 | Information not present in EudraCT |
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
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
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 | 3 |