E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Disease to be investigated: 12 patients with severe chronic urticaria (CU) with or without angioedema which continously need medical treatment
As a control: 6 patients with atopy syndrome consisting of atopic dermatitis (AD) and/or allergic rhinoconjunctivits and allergic asthma which continously need medical treatment
As an additional control: 6 healthy volunteers (1 blood sample, 1 skin sample, no Xolair treatment) |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10009159 |
E.1.2 | Term | Chronic urticaria |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10021247 |
E.1.2 | Term | Idiopathic urticaria |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003639 |
E.1.2 | Term | Atopic dermatitis |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10031673 |
E.1.2 | Term | Other atopic dermatitis and related conditions |
|
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 |
Severe chronic urticaria (CU) or atopic dermatitis (AD) are burdening diseases. Continuous medication is required, quality of life is low. In the proposed trial we plan to treat 12 CU- and 6 AD-patients with Xolair which is an established drug for treatment of severe asthma, but not approved for CU/AD. However, multiple case reports and case series demonstrated a benefit for these patients. Omalizumab, therefore, is part of the EAACI/GA2LEN/EDF/WAO guidline for management of CU [Allergy 2009:64:1427-1443]. Protocol: Treatment with 4 x 300 mg Xolair at week 0, 4, 8, 12 s.c. (in the Xolair-range approved for asthma). Blood sampeling at week 0, 4, 8, 12, 16, skin punch biopsies (6 mm) from uninvolved / involved skin at week 0, 16 and after the first clinical effect. Clinical scores, quality of life, amount of co-medication and safety measures at week 0, 4, 8, 12, 16. Main objective: significant improvement of clinical symptoms and/or quality of life and/or amount of co-medication. |
|
E.2.2 | Secondary objectives of the trial |
In mast cells and basophilic granulocytes of patients with CU, for various stimuli the signal threshold which has to be reached to induce degranulation is lower as compared to healthy individuals, and hyperreleasability of granules is a well known phenomenon. To be clinically effective, Xolair has to normalize these alterations in the long run, i.e. has to directly or indirectly "calm down" the degranulation machinery. This hypothesis can be tested. Determination of degranulation thresholds before/during omalizumab-therapy will be the main scientific focus of the project: Analysis of intracellular composition of granules, changes before/during therapy and analysis of the signal transduction molecules governing degranulation, changes before/during therapy.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Persistent or intermittent symptoms of chronic urticaria and/or angioedema for at least 6 weeks despite treatment with antihistamines according to level 3 of the treatment algorithm of the international guidline for the management of urticaria [Zuberbier T. et al. (2009) EAACI/GA2LEN/EDF/WAO guideline: Management of urticaria. Allergy 2009: 64: 1427-1443]
- Persistent symptoms of atopic dermatitis with or without allergic asthma despite treatment with antihistamines and/or topical application of steroids
- The patient is able to understand the study, capable to give informed consent and available for 16 weeks of the trial
- Age > 18
- Written informed consent
|
|
E.4 | Principal exclusion criteria |
- Hypersensitivity against Omalizumab or one of the other contents of Xolair
- Acute exacerbation of asthma, acute bronchospasms, asthmatic status
- pregnancy or breast feeding
- Age below 18
- Systemic steroids or other immunosuppressants 4 weeks before Xolair-treatment
- Severe disease e.g. cancer, AIDS, Hepatitis B/C, severe autoimmune diseases, severe liver- and/or kidney-dysfunction, insulin dependent diabtes mellitus or parasite (worm) infections
- Treatment/pretreatment with Xolair
- non-compliance and/or unability to understand necessary information for the trial |
|
E.5 End points |
E.5.1 | Primary end point(s) |
There primary clinical end point is the clinical effect after 16 weeks of treatment.
The primary study parameter is the dynamics of degranulation of mast cells /and or basophilic granulocytes before/during/after treatment.
|
|
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 | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
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 |
investigate granule dynamics |
|
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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
|
The clinical part of the study will end after the last included individual has completed its last visit. The laboratory work will continue for approximately another 12 month. |
|
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 | 6 |
E.8.9.1 | In the Member State concerned days | 30 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |