E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
severe persistent non-atopic asthma |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003553 |
E.1.2 | Term | Asthma |
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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 study the change from baseline in the expression of FcεRI receptors of blood basophils and dendritic cells after 16 weeks of treatment with omalizumab as compared with placebo. |
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E.2.2 | Secondary objectives of the trial |
Efficacy : • To study the change in fractional exhaled nitric oxide (FeNO) after 4, 8, 12 and 16 weeks of treatment with omalizumab as compared with placebo (using the Niox Mino® device). • To study the change from baseline in induced sputum eosinophil count after 16 weeks of treatment with omalizumab as compared with placebo (in a subset of patients in selected centers). Safety : • To assess safety of omalizumab with regard to adverse events and weight.
See other objectives in the protocol page 12-13.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Outpatients who have been informed of the study procedures and medications and have given written informed consent prior to initiation of any study-related procedure. 2. Who are ≥ 18 and ≤ 70 years of age. 3. With a severe persistent asthma with the following characteristics: i. FEV1 < 80% of predicted. ii. Uncontrolled according to GINA 2007 guidelines (cf. Appendix 1) and at least 2 exacerbations having required systemic corticosteroid and/or at least 1 hospitalization or emergency room visit in the past year. iii. Treated with high-dose inhaled corticosteroid (i.e. > 1,000 µg beclometasone dipropionate equivalent per day) (cf. Appendix 2) plus inhaled long-acting β2 agonist (with or without maintenance oral corticosteroid). iv. Non-atopic as defined by the EGEA Cooperative Group, i.e. negative blood multiallergic testing (ImmunoCAP® Phadiatop) and negative skin prick tests to a battery of common aeroallergens [dust mites (Dermatophagoides pteronyssinus, Dermatophagoides farinae), cat and dog dander, cockroaches (Blatella germanica), molds (Alternaria, Cladosporium, Aspergillus), and pollens of ragweed, birch tree, olive tree, timothy grass and Parietaria], demonstrated at Visit 1. Prick tests are considered negative if 15-20 minutes after allergen injection the mean diameter of wheal is < 3 mm and the wheal index (mean diameter of wheal/mean diameter of positive control) is < 0.5. Detailed skin prick test procedures can be found in Appendix 3. 4. With a body weight ≥ 20 kg and ≤ 150 kg, and a serum total IgE level ≥ 30 and ≤ 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.
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E.4 | Principal exclusion criteria |
1. Current smokers or smoking history stopped for less than 3 years or > 10 pack years. 2. Patients who have been treated for an asthma exacerbation during the 4 weeks prior to randomization. 3. Patients with an active lung disease other than non-atopic asthma (e.g.: allergic bronchopulmonary aspergillosis, COPD). 4. Patients with an active cancer, a suspicion of cancer or any history of cancer with less than 5 disease free years. 5. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/mL). 6. Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and 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). 7. Patients who are receiving methotrexate, gold salts, cyclosporine, anti-TNF therapy or troleandomycin within 3 months of Visit 1 or anticipate their use during the study. 8. Patients treated with omalizumab (currently or in the past). 9. Patients with aspirin or non steroidal anti-inflammatory drug (NSAID) related asthma diagnosed from the patients history. Patients can be included if use of aspirin or NSAIDs will be avoided for the entire duration of the study. 10. Patients who have been treated with investigational drugs over the past 30 days or within 5 half-lives of the investigational drug prior to Visit 2, whichever comes first. 11. Patients who are considered potentially unreliable or where it is envisaged the patient may not consistently attend scheduled study visits. 12. Patients with any other condition or prior/current treatment, which in the opinion of the investigator renders the patient ineligible for the study schedule.
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E.5 End points |
E.5.1 | Primary end point(s) |
To study the change from baseline in the expression of FcεRI receptors of blood basophils and dendritic cells after 16 weeks of treatment with omalizumab as compared with placebo. |
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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 | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Effect of omalizumab on the expression of FcεRI receptors of blood basophils and dendritic cells |
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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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
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 | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | |