| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 8.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10009159 |
| E.1.2 | Term | Chronic urticaria |
|
| 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 demonstrate that omalizumab, compared to omalizumab-Placebo, has superior efficacy as for urticaria activity score (UAS7) after 24 weeks of treatment in adult patients with moderate to severe chronic urticaria who exhibit IgE against thyreoperoxidase. |
|
| E.2.2 | Secondary objectives of the trial |
To evaluate whether omalizumab is superior to omalizumab-Placebo on:
Daily scores for wheals, pruritus, erythemas, angioedemas, systemic symptoms
standardized UAS AUC over 24 weeks
Use of concomitant and rescue medication (loratadine, clemastine)
Quality of Life [DLQI and Skindex]
Chronic Urticaria Quality of Life Questionnaire [Cu-Q2oL]
Patient’s Global assessment of symptoms
Investigator’s Global Assessment of symptoms
|
|
| 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. males or females of any race
3. who are 18-70 years of age
4. with a body weight ≥ 20 kg and ≤ 150 kg and with a total serum IgE level ≥ 30 IU/mL and ≤ 700 IU/mL (suitable weight for dosing as provided in Tables 6-1 and 6-2) at the time of pre-screening
5. with a specific serum IgE anti-TPO level of ≥ 5.0 IU/mL, documented within the last 3 months prior to randomization or at the time of pre-screening
6. with the diagnose of moderate to severe chronic urticaria according to the EAACI/GA2LEN/EDF guideline (Zuberbier 2006a, Zuberbier 2006b) at the time of screening, i.e. recurrent wheal and flare type skin reactions and pruritus ≥ 6 consecutive weeks despite using antihistamines
7. Subject’s current episode of chronic urticaria has not responded to the approved marketed dose of antihistamine for two weeks or longer and is sufficiently symptomatic at the time of visit 1 to qualify for this study
8. with an urticaria activity score (UAS) > 0 at any of the 7 days of the first section of the screening period (week -3)
9. with an urticaria activity score (UAS7) ≥ 10 at the time of randomization (visit 2)
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|
| E.4 | Principal exclusion criteria |
Females of childbearing potential: pregnancy, birth control, breast-feeding
1. 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)
2. Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual ori-entation precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means, UNLESS they meet the following defini-tion of post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels >40 mIU/m or 6 weeks post surgi-cal bilateral oophorectomy with or without hysterectomy or hysterectomy OR are us-ing one or more of the following acceptable methods of contraception: surgical sterili-zation (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).
Other therapies/medication
3. who have taken oral or parenteral corticosteroids, methotrexate, cyclosporine, or other immunosuppressant medications during the 4 weeks prior to visit 1 or during the screening phase or who have taken intravenous immunoglobulin (IVIG) during the 3 months prior to Visit 1 or during the screening phase
4. concomitant treatment with substances interfering with the immune system.
Concurrent diseases/conditions and history of other diseases/conditions
5. with permanent severe diseases, especially those affecting the immune system, except CU and stable thyroid disease
6. presence of acute urticaria, angioedema, or larynx edema
7. with a history of food or drug related severe anaphylactoid or anaphylactic reaction(s)
8. the presence of permanent gastrointestinal condition which may influence the oral therapy (chronic diarrhoea diseases, congenital malformations or surgical mutilations of gastrointestinal tract)
9. with a history or presence of epilepsy, significant neurological disorders, cerebrovascular attacks or ischemia
10. with a history or presence of myocardial infarction or cardiac arrhythmia which requires drug therapy
11. with elevated serum IgE levels for reasons other than allergy and/or urticaria (e.g.: parasite infections, hyperimmunoglobulin E syndrome, Wiskott-Aldrich Syndrome or clinical allergic bronchopulmonary aspergillosis).
12. evidence of severe renal dysfunction
13. evidence of significant hepatic disease
14. history of malignancy of any organ system, treated or untreated, whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin
15. with clinically significant laboratory abnormalities (not associated with the study indi-cation) at Visit 1
Investigational drug/therapy use
16. who have previously been randomized into this or any other omalizumab study or who have received omalizumab (prescribed).
17. Use of other investigational drugs at the time of enrolment, or within 30 days or 5 half lifes of enrolment, whichever is longer.
Ingredient hypersensitivity
18. with known hypersensitivity to any ingredients, including excipients (sucrose, histidine, polysorbate 20) of the study medication or drugs related to omalizumab (e.g.: monoclonal antibodies, polyclonal gammaglobulin) or with known hypersensitivity to the trial’s rescue- or escalation-medication or related drugs (e.g.: loratadine, clemastine).
Compliance, reliability and investigator judgment
19. who are considered potentially unreliable or where it is envisaged the patient may not consistently attend scheduled study visits
20. with serious psychiatric and/or psychological disturbances.
21. with a history of drug or alcohol abuse.
22. who are unable to complete a patient diary or complete questionnaires on paper
23. with any other condition or prior/current treatment, which in the opinion of the inves-tigator renders the patient ineligible for the study schedule.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| UAS7 at study end; Urticaria activity score (UAS),a composite diary-recorded score. |
|
| 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 | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| 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 | 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.8.5 | 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
|
|
| 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 | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| 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 |
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