E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Spontaneous Urticaria |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10072757 |
E.1.2 | Term | Chronic spontaneous urticaria |
E.1.2 | System Organ Class | 10040785 - Skin and subcutaneous tissue disorders |
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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 demonstrate the superiority of omalizumab 300 mg and / or 150 mg injected subcutaneously every 4 weeks in patients with refractory CSU receiving concomitant H1AH therapy with respect to a reduction from baseline in the weekly itch severity score at Week 12, compared to placebo |
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E.2.2 | Secondary objectives of the trial |
•To demonstrate that patients with refractory CSU receiving concomitant H1AH who are treated by omalizumab 300 mg and / or 150 mg have a greater reduction from baseline in urticaria activity score 7 (UAS7), weekly number of hives score, weekly largest hive score, and Dermatology Life Quality Index (DLQI) at Week 12 relative to placebo-treated patients.
•To demonstrate that a greater proportion of patients with refractory CSU receiving concomitant H1AH who are treated by omalizumab 300 mg and / or 150 mg to have UAS7 ≤ 6 and to achieve itch severity score minimally important difference (MID) response and UAS7 = 0 at Week 12 relative placebo treated patients
•To evaluate the safety of omalizumab including incidence and severity of adverse events and serious adverse events, vital signs and clinical laboratory evaluation, and anti omalizumab antibody at the end of the study. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Diagnosis of chronic spontaneous urticaria refractory to H1 antihistamine at the time of randomization
- Chronic spontaneous urticaria diagnosis for 6 months
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E.4 | Principal exclusion criteria |
•Weight less than 20 kg
•Clearly defined underlying etiology for chronic urticaria other than chronic spontaneous urticaria
•Evidence of parasitic infection
•Any other skin diseases than chronic spontaneous urticaria with chronic itching
•Previous treatment with omalizumab
•Contraindications to diphenhydramine
•History of anaphylactic shock
•History or current diagnosis of ECG abnormalities indicating significant risk of safety for patients participating in the study
•History of hypersensitivity to omalizumab or to drugs of similar chemical classes
•Pregnant or nursing (lactating) women
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E.5 End points |
E.5.1 | Primary end point(s) |
Change From Baseline to Week 12 in the Weekly Itch Severity Score.
The weekly itch severity score is the sum of the daily itch severity scores over 7 days and ranges from 0 to 21. The daily itch severity score is the average of the morning and evening scores on a scale of 0 (none) to 3 (severe). The Baseline weekly itch severity score is the sum of the daily itch severity scores over the 7 days prior to the first treatment. A higher itch severity score indicates more severe itching. A negative change score indicates improvement. |
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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) |
1. Change From Baseline to Week 12 in the Urticaria Activity Score Over 7 Days (UAS7).
The UAS7 is the sum of the daily urticarial activity scores over 7 days and ranges from 0 to 42. The daily urticarial activity score is the average of the morning and evening urticarial activity scores and ranges from 0 to 6. The urticarial activity score is the sum of ratings on a scale of 0 to 3 (0=none to 3=intense/severe) for (1) the number of wheals (hives) and (2) itch intensity over the previous 12 hours, ranges from 0 to 6, and is measured twice daily (morning and evening). The Baseline score is the sum of the daily urticarial activity scores over the 7 days prior to the first treatment. A higher urticarial activity score indicates more urticaria activity. A negative change score indicates improvement.
2. Change From Baseline to Week 12 in the Weekly Number of Hives Score.
The weekly hives score is the sum of the daily hives scores over 7 days and ranges from 0 to 21. The number of hives is measured twice daily (morning and evening) on a scale of 0 (none) to 3 (> 12 hives per 12 hours). The daily hives score is the average of the morning and evening scores. The Baseline score is the sum of the daily hives scores over the 7 days prior to the first treatment. A higher score indicates more hives. A negative change score indicates improvement.
3. Percentage of Participants With a UAS7 Score ≤ 6 at Week 12.
4. Change From Baseline to Week 12 in the Weekly Size of the Largest Hive Score.
The weekly size of the largest hive score is the sum of the daily size of the largest hive scores over 7 days and ranges from 0 to 21. The daily size of the largest hive score is assessed twice daily (morning and evening) on a scale of 0 (none) to 3 (> 2.5 cm). The daily size of the largest hive score is the average of the morning and evening scores. The Baseline weekly size of the largest hive score is calculated over the 7 days prior to the first treatment. A higher score indicates larger hives. A negative change score indicates a reduction in hive size.
5. Percentage of Weekly Itch Severity Score Minimally Important Difference (MID) Responders at Week 12.
The MID response is defined as a reduction ≥ 5 points from Baseline in the weekly itch severity score.
6. Percentage of Complete Responders (UAS7 = 0) at Week 12.
7. Change From Baseline in the Overall Dermatology Life Quality Index (DLQI) Score at Week 12.
The DLQI is a 10-item dermatology-specific health-related quality of life measure. Patients rated their dermatology symptoms as well as the impact of their skin condition on various aspects of their lives on a scale of 0 (Not at all) to 3 (Very much). The overall DLQI is the sum of the responses to the 10 items and ranges from 0 to 30. A lower score indicates a better quality of life. A negative change score indicates improvement.
8. Percentage of Participants With Adverse Events.
The percentage of participants with serious adverse events and other adverse events is summarized by MedDRA preferred terms and organ classes in the Reported Adverse Events section.
9. Percentage of Participants with production of anti-omalizumab antibody.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Points 1,2, 4, 5, 7: Baseline to Week 12
Point 3, 6 : Week 12
Point 8: Up to Week 24
Point 9: Week 24 |
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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 | No |
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 | 3 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA 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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 1 |