Efficacy and Safety of Omalizumab in Adults (18-70 Years) With Moderate to Severe Chronic Urticaria

Study Overview
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Brief Summary
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This study evaluated the safety and efficacy of omalizumab in adult patients with moderate to severe chronic urticaria who exhibit IgE against thyroperoxidase.

Official Title
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A Randomized, 24 Weeks, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Assess the Efficacy and Safety of Omalizumab in Adult Patients With Chronic Urticaria Who Exhibit IgE Against Thyroperoxidase

Conditions
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Chronic Urticaria

Intervention / Treatment
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* Drug: Omalizumab 75-375 mg
* Drug: Placebo to omalizumab
* Drug: Loratadine
* Drug: Clemastine


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Males or females from 18-70 years of age Body weight ≥ 20 kg and ≤ 150 kg and with a total serum IgE level ≥ 30 IU/mL and ≤ 700 IU/mL Specific serum IgE anti-TPO level ≥ 8.0 IU/mL, documented within 3 months prior to randomization or time of pre-screening Diagnosis of moderate to severe chronic urticaria Subject's current episode of chronic urticaria according to the European Academy of Allergology and Clinical Immunology/Global Allergy and Asthma European Network/European Dermatology Forum (EAACI/GA2LEN/EDF) guideline at the time of screening Current episode of chronic urticaria has not responded to the approved marketed dose of antihistamine for 2 weeks or longer Urticaria activity score (UAS) ≥ 0 at any of the 7 days of the first section of the screening period UAS7 ≥ 10 at the time of randomization Exclusion criteria: Females of child-bearing potential or breast feeding Present or past medical conditions that could have interfered with the study results Randomized into any other omalizumab study or who had received omalizumab Received investigational drugs within 30 days of enrollment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Omalizumab 75-375 mg<br>Omalizumab was dosed at 75 to 375 mg according to baseline IgE and body weight as described in dosing tables in the study protocol. Dosing occurred subcutaneously every 2 or 4 weeks depending on dose. | Drug: Omalizumab 75-375 mg<br>* Omalizumab was supplied as lyophilized, sterile powder in a single-use, 5 ml vial designed to deliver 150 mg of omalizumab upon reconstitution with 1.4 ml sterile water for injection.<br>* Other names: Xolair;Drug: Loratadine<br>* All participants received antihistamines on demand (loratadine and clemastine), as the trial was designed to investigate the effect of omalizumab as an add-on to antihistamines in people with chronic urticaria (CU). Administration of antihistamines is the current gold standard treatment of CU. A significant proportion of people with CU is not well controlled by this standard or by using high doses of antihistamines.<br>* Other names: Lorano®;|
| Placebo Comparator: Placebo to omalizumab<br>Placebo to omalizumab was dosed at 75 to 375 mg according to baseline IgE and body weight as described in dosing tables in the study protocol. Dosing occurred subcutaneously every 2 or 4 weeks depending on dose. | Drug: Placebo to omalizumab<br>* Placebo to omalizumab was supplied as lyophilized, sterile powder in a single-use, 5 ml vial designed to deliver 150 mg placebo to omalizumab upon reconstitution with 1.4 ml sterile water for injection.<br>Drug: Loratadine<br>* All participants received antihistamines on demand (loratadine and clemastine), as the trial was designed to investigate the effect of omalizumab as an add-on to antihistamines in people with chronic urticaria (CU). Administration of antihistamines is the current gold standard treatment of CU. A significant proportion of people with CU is not well controlled by this standard or by using high doses of antihistamines.<br>* Other names: Lorano®;Drug: Clemastine<br>* All participants received antihistamines on demand (loratadine and clemastine), as the trial was designed to investigate the effect of omalizumab as an add-on to antihistamines in people with chronic urticaria (CU). Administration of antihistamines is the current gold standard treatment of CU. A significant proportion of people with CU is not well controlled by this standard or by using high doses of antihistamines.<br>* Other names: Tavegil®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Weekly Urticaria Activity Score (UAS7) From Baseline to the End of the Study (Week 24) | The UAS is a composite diary-recorded score with numeric severity ratings (0=none to 3=intense) for the number of wheals per 24 hours and the intensity of the pruritus. The total daily score (sum of the wheal and pruritus scores) ranges from 0 to 6. Because of variations in chronic urticaria disease intensity, assessment of disease activity was based on a weekly (7 days) UAS score called UAS7, that is, the sum of the daily UASs, ranging from 0 to 42 per week. A higher score indicates worse disease. A negative change score (Week 24 score minus Baseline score) indicates improvement. | Baseline to end of the study (Week 24) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Wheals, Erythemas, Pruritus, and Angioedemas at the End of the Study | Patients kept a daily diary of the number of wheals and erythema and the severity of pruritus and angioedemas during the study. | At the end of the study (Week 24) | 
| Standardized (With Respect to Length of Time) Area Under the Curve (AUC) for the Urticaria Activity Score (UAS) From Baseline to the End of the Study (Week 24) | The UAS is a composite diary-recorded score with numeric severity ratings (0=none to 3=intense) for the number of wheals per 24 hours and the intensity of the pruritus. The total daily score (sum of the wheal and pruritus scores) ranges from 0 to 6. A higher score indicates worse disease. AUC was calculated from daily UASs where no urticaria medication was taken using the trapezoidal rule. The standardized AUC UAS was calculated as the sum of trapezoids divided by the length of time. | Baseline to the end of the study (Week 24) | 
| Use of Concomitant and Rescue Medications | Data was collected from the patients' diaries about the number of clemastine and loratadine pills taken during the last 7 days of each month of the study. | At Weeks 4, 8, 12, 16, 20, and 24 | 
| Change in the Dermatology Life Quality Index (DLQI) Score From Baseline to the End of the Study (Week 24) | The DLQI is a dermatology-specific quality of life (QoL) questionnaire designed for use in patients over 16 years of age. Patients are asked to respond to each of 10 questions on a 4-point Likert scale in regard to how much their skin problem has affected their life over the last week (0=not at all, 1=a little, 2=a lot, 3=very much). The overall (total) DLQI score (range=0 to 30) is calculated by summing the scores of all 10 questions. The higher the score, the more QoL is impaired. A negative change score (Week 24 score minus Baseline score) indicates improvement. | Baseline to the end of the study (Week 24) | 
| Change in the Skindex Score From Baseline to the End of the Study (Week 24) | Skindex is a 30-item questionnaire with 3 scores (functioning, emotions,symptoms) and a composite score (average scale score) that assesses the effects of skin disease on patients' quality of life (QoL). Item responses are standardized on a scale from 0 to 100. The mean of all 61 items was calculated. A higher score indicates a lower QoL. A negative change score (Week 24 score minus Baseline score) indicates improvement. | Baseline to the end of the study (Week 24) | 
| Change in Chronic Urticaria Quality of Life (CU-Q2oL) Scores From Baseline to the End of the Study (Week 24) | The CU-Q2oL (German version) is a questionnaire that measures the relative burden of chronic urticaria on subjective well-being. It has 23 questions in 3 domains (symptoms, general impairment, difficulties and problems due to urticaria). Patients are asked to respond how much they are troubled by each problem on a 5-point Likert scale (1=not at all to 5=very much). Each domain and the overall (total) scores are normalized to a scale of 1 to 100. A higher score indicates lower QoL. A negative change score (Week 24 score minus Baseline score) indicates improvement. | Baseline to the end of the study (Week 24) | 
| Patient's Global Assessment of Their Chronic Urticaria Symptoms | Patients made a global assessment of their chronic urticaria symptoms on a 4-point Likert scale (none, mild moderate, severe) at Baseline and again at the end of the study. The number of patients in each category is reported. | At Baseline and at the end of the study (Week 24) | 
| Investigator's Global Assessment of the Patient's Chronic Urticaria Symptoms | The investigator made a global assessment of the patient's chronic urticaria symptoms on a 4-point Likert scale (none, mild, moderate, severe) at Baseline and again at the end of the study. The number of patients in each category is reported. | At Baseline and at the end of the study (Week 24) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic urticaria, omalizumab, thyroperoxidase, IgE