E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 explore the effect of 78-weeks therapy with omalizumub compared to placebo on the number of sub-epithelial eosinophils, a marker of airway inflammation, in patients with resistent moderate to severe allergic asthma. |
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E.2.2 | Secondary objectives of the trial |
To explore the effect of 78 weeks therapy with omalizumab compared to placebo on sub-epithelial mast cells and CD4+ T-lymphocytes, as markers of airway inflammation and the thickness of the reticular basement membrane, as a marker or air modeling, assessed in bronchial biopsies. To assess the safety and tolerability of 78 weeks therapy with omalizumab, compared to placebo.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. patients who have been informed of the study procedures and medications and have given written informed consent 2. who are 18 - 75 years of age and are considered fit to undergo bronchoscopy by the investigator 3. with a body weight ≥ 20 kg and ≤ 150 kg and with a serum total IgE level ≥ 30 to ≤ 700 IU/ml. The combination of body weight and serum total IgE level must fall within the dosing cells of the approved European dosing tables (Table 6-1 and 6-2) 4. patients with moderate to severe allergic asthma, with persistent symptoms despite receiving an inhaled corticosteroid and long acting beta-agonist (i.e. Step 4 or 5 treatment as per 2006 GINA guidelines – Appendix 3) 5. with ≥ 2% eosinophilia in induced sputum at visits 1 and 2 6. with a positive skin prick test (diameter of wheal ≥ 3 mm) or RAST test to at least one perennial aero-allergen, excluding molds (eg. dust mite, cat/dog dander, cockroaches), documented within the past 2 years or demonstrated at Visit 1, to which the patient will be exposed on a regular basis (most days) for the duration of the study. 7. A RAST test may be performed for patients with a borderline skin prick test result. Patients with a total IgE level of ≤ 76 IU/mL require an unequivocal positive RAST test (>71 IU/mL; Class 2+) to be eligible. Skin prick test procedures can be found in Appendix 6 8. with a post-bronchodilator FEV1 ≥60% of the predicted normal value for the patient, demonstrable 15 minutes after the patient receives 400mcg of salbutamol (or equivalent) at Visit 1. FEV1 % predicted must be stable (within 10%) at the second screening visit (Visit 2) and the randomization visit (Visit 3) 9. receiving moderate to high dose inhaled corticosteroid ≥ 800μg per day BDP or equivalent, as monotherapy or fixed dose combination, and a regular inhaled long acting β-2 agonist at stable doses for at least 3 months prior to screening
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E.4 | Principal exclusion criteria |
1. Females of childbearing potential: - Pregnant or nursing (lactating) women as defined by the protocol. - Women of child-bearing potential (WOCBP), as defined by the protocol. - women whose partners have been sterilized by vasectomy or other means, unless they meet the following definition of post-menopausal: at least 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels >40 mIU/m or at least 6 weeks post surgical bilateral oophorectomy with or without hysterectomy or hysterectomy OR are using one or more of the following acceptable methods of contraception: surgical sterilization (e.g., bilateral tubal ligation, vasectomy), hormonal contraception (implantable, patch, oral), and double-barrier methods (any double combination of: IUD, male or female condom with spermicidal gel, diaphragm, sponge, cervical cap) 2. Other therapies/medication: - patients who do not adhere to the antihistamine washout prior to the skin prick tests at Visit 1 as described in the protocol. - patient taking short acting antihistamines, medium acting antihistamines as defined in the protocol. - patients receiving: ß-adrenergic antagonist medication (e.g.: propranolol) or anticipate use during the study, methotrexate, gold salts, cyclosporin or troleandomycin within 3 months of Visit 1 or anticipate their use during the study, desensitization therapy with less than 3 months of stable maintenance doses prior to the screening visit (Visit 1). - patients who have received omalizumab previously 3. Concurrent diseases/conditions and history of other diseases/conditions: - patients who have been treated for a clinically significant asthma exacerbation during the 4 weeks prior to randomization - with a history of: food or drug related severe anaphylactoid or anaphylactic reaction(s) - allergy to antibiotics. Patients may be included if the antibiotics to which they are allergic will be avoided for the duration of the study - with aspirin or non steroidal anti-inflammatory drug (NSAID) related asthma diagnosed from the patients history. Patients can be included if use of NSAIDs will be avoided for the entire duration of the study - who are current smokers, stopped smoking within the last 12 months, or have a smoking history > 10 pack years - with an active lung disease other than allergic asthma (e.g.: chronic bronchitis, COPD) - with elevated serum IgE levels for reasons other than allergy (e.g.: parasite infections, hyperimmunoglobulin E syndrome, Wiskott-Aldrich Syndrome or clinical allergic bronchopulmonary aspergillosis) - with active cancer or a history of cancer. Localized basal cell carcinoma (without metastases) of the skin is acceptable. - patients 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 - with a lower respiratory tract infection within 1 month of Visit 1 or an upper respiratory tract respiratory infection that does not resolve after 7-10 days. - with clinically significant abnormality on a 12-lead ECG recorded within one month prior to or at Visit 1 - with clinically significant laboratory abnormalities (not associated with the study indication) at Visit 1 4. Investigational drug/therapy use: - who have been treated with investigational drugs over the past 30 days or within 5 half-lives of the investigational drug, whichever comes first 5. Ingredient hypersensitivity: - with known hypersensitivity to any ingredients, including excipients of the study medication or drugs related to omalizumab - with hypersensitivity to the trial’s asthma rescue medication or related drugs 6. Compliance, reliability and investigator judgment: - who are considered potentially unreliable or where it is envisaged the patient may not consistently attend study visits - with a history of drug or alcohol abuse - who are unable to perform spirometry, peak flow measurements, complete patient diary or note book or complete questionnaires on paper and over the telephone. - involved in disease-related litigation 7. Exclusion criteria for flexible fiberoptic bronchoscopy - history of allergic reactions to local anesthetics to be used in the procedure • any clotting abnormality • acute myocardial infarction, unstable angina and other relevant medical conditions deemed appropriate by the investigator • history of chronic CO2 retention • a patient who, in the judgment of the investigator is considered to be unsuitable for bronchoscopy
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E.5 End points |
E.5.1 | Primary end point(s) |
The number of tissue sub-epithelial eosinophils following 78 weeks treatment. |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | Yes |
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 | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
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 |
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E.8.7 | Trial has a data monitoring committee | No |
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
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Last visit of the past patient |
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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 | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |