E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
moderate to severe chronic spontaneous urticaria with angioedema |
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E.1.1.1 | Medical condition in easily understood language |
moderate to severe chronic spontaneous urticaria with angioedema |
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E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10009159 |
E.1.2 | Term | Chronic urticaria |
E.1.2 | System Organ Class | 100000004858 |
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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 |
The primary objective is to demonstrate the superiority of omalizumab 300 mg versus placebo in patients with moderate to severe CSU regarding QoL measures. This will be done by evaluating the change of total CU-Q2oL scores in moderate to severe CSU patients with a history of angioedema and insufficient treatment response to a high dose of nsH1-antihistamines (second line treatment: up to 4x of the approved nsH1-Antihistamine dose). Scores will be calculated from baseline (visit 2) to week 28 (visit 9) with secondary objective(s). |
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E.2.2 | Secondary objectives of the trial |
Angioedema burdened days
Angioedema Activity Score (AAS)
AE-Q2oL (Angioedema Quality-of-Life Score)
Time to first angioedema episode following initiation of study therapy
Time interval between successive angioedema episodes following initiation of therapy
Time to first recurrence after discontinuation of omalizumab /placebo therapy within follow-up period
Need for sedating H1-antihistamine and corticosteroids based rescue medication (as specified under 6.6.4)
UAS7 (weekly Urticaria Activity Score)
DLQI (Dermatology Quality of Life Index)
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patient is informed about study procedures and medications and has given written informed consent before any assessment.
2. Patient is able to communicate with the investigator, understands and complies with the requirements of the study.
3. Male or Female of any race aged 18-75 years
4. Diagnosis of chronic spontaneous urticaria (CSU) refractory to H1 antihistamines at Baseline (Day -14) based on patient’s medical history, as defined by all of the following:
• The presence of itch and hives for > 6 weeks
• UAS7 score (range 0−42) ≥ 14
5. Patient has a history of insufficient response to 4x of the approved dose of nsH1-antihistamines.
6. Patients on high dose nsH1-antihistamine (2-4x of the approved dose) for at least 3 consecutive days immediately prior to the Day -14 screening visit (current use must be documented on the day of screening visit).
7. CU-Q2oL Score ≥ 30 at baseline
8. CSU diagnosis for ≥ 6 months
9. CSU with occurrence of angioedema at least 4x in the last 6 months
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E.4 | Principal exclusion criteria |
1. Patients with non urticaria associated angioedema
2. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of the compound, whichever is longer
3. History of hypersensitivity to any of the study drugs (omalizumab) or rescue medication or to drugs of similar chemical structures.
4. Evidence of parasitic infection.
5. Atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus or other skin disease associated with itch.
6. Previous treatment with omalizumab within 6 months prior to screening.
7. Treatment with defined comedications
8. History of anaphylactic shock.
9. Presence of clinically significant cardiovascular, bronchial, neurological, psychiatric, metabolic or other pathological conditions that could interfere with the interpretation of the study results and or compromise the safety of the patients.
10. Medical examination or laboratory findings that suggest the possibility of decompensation of co-existing conditions.
11. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
12. Women who are pregnant or breast feeding or capable of becoming pregnant and not practicing a medically approved method of contraception1.
15. Permanent severe diseases, especially those affecting the immune system, except CSU.
16. Presence of permanent gastrointestinal condition which may influence the oral therapy (chronic diarrhea diseases, congenital malformations or surgical mutilations of gastrointestinal tract).
17. History or presence of epilepsy, significant neurological disorders, cerebrovascular attacks or ischemia.
18. History or presence of myocardial infarction or cardiac arrhythmia which requires drug therapy.
19. Evidence of severe renal dysfunction.
20. Evidence of significant hepatic disease.
21. Patient considered potentially unreliable or where it is envisaged the patient may not consistently attend scheduled study visits.
22. Serious psychiatric and/or psychological disturbances.
23. History of drug or alcohol abuse.
24. Patient unable to complete a patient diary or complete questionnaires on paper.
25. Any other condition or prior/current treatment, which in the opinion of the investigator renders the patient ineligible for the study schedule.
12.26. Patients, who have already been randomized into this trial earlier must not be included a second time.
13.27. Study personnel or first degree relatives of investigator(s) must not be included in the study.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary variable is the change from baseline to week 28 of the CU-Q2oL questionnaire. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
The AAS, AE-Q2oL, UAS7 and DLQI will be analyzed analogous to the primary endpoint, as a mean difference from baseline (visit 2) to week 28 (visit 9). Time courses will be displayed descriptively and graphically. For these analyses, values of patients requiring rescue medication will not be used for 6 weeks (resp. 4 weeks for the DLQI) following the last corticosteroid intake. Other secondary or exploratory objectives (e.g. rescue medication use, angioedema burdened days) will be summarized descriptively by treatment group. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 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) | 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.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 26 |
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 | No |
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 | 8 |
E.8.9.1 | In the Member State concerned days | 0 |