Impact of Omalizumab on Quality of Life Measures and Angioedema Occurrence in Patients With CSU Refractory to Therapy

Study Overview
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Brief Summary
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This study will assess the impact of omalizumab on the quality of life improvement when added to the standard therapy in refractory patients suffering from chronic spontaneous urticaria and angioedema.

Detailed Description
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This study will be conducted using a double-blind, placebo-controlled, randomized, multicenter design to investigate the impact of omalizumab on Quality of Life (QoL) in Chronic Spontaneous Urticaria (CSU) and will assess its effectiveness in reducing and/or inhibiting the occurrence, time-course and severity of angioedema episodes. Omalizumab is administered subcutaneously every 4 weeks as an add-on therapy to the current approved treatment of adult CSU patients. The treatment period is 28 weeks which is followed by an 8-week follow-up. The study aims to enroll approximately 70 patients. The study is divided into a 2-week screening period, a 28-week double-blind treatment phase with omalizumab or placebo-omalizumab, and an 8-week follow-up phase.

Official Title
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A Randomized, Double-blind, Placebo-controlled, 28-week Treatment With a 8 Week Follow-up to Investigate the Impact of Omalizumab on Quality of Life Measures and the Incidence and Severity of Angioedema Despite H1-antihistamine Therapy.

Conditions
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Chronic Spontaneous Urticaria, Angioedema

Intervention / Treatment
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* Biological: Omalizumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of chronic spontaneous urticaria (CSU) refractory to H1-antihistamine treatment Presence of itch an hives for more than 6 weeks UAS7 score of more than 14 (range 0-42) Patient has history of insufficient response to 4x of the approved dose of H1-antihistamines CSU diagnosis for more than 6 months Angioedema at least 4x in the last 6 months Exclusion Criteria: Patients with non urticaria associated angioedema History of hypersensitivity to omalizumab or the rescue medication or to drugs of similar chemical structure Evidence of parasitic infection Previous treatment with omalizumab within the last 6 months prior to screening History of anaphylactic shock Woman who are pregnant or breast feeding Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1 Omalizumab<br>omalizumab once a month via subcutaneous injection. | Biological: Omalizumab<br>* Humanized monoclonal antibody against human IgE<br>* Other names: IGE025;|
| Placebo Comparator: 2 Placebo<br>placebo of omalizumab once a month via subcutaneous injection | Drug: Placebo<br>* Placebo to omalizumab<br>* Other names: Placebo for Omalizumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline Using Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) Total Scores During the Study: Unadjusted Analysis and ANCOVA (LOCF) (FAS) | The CU-Q2oL is a questionnaire that measures the relative burden of chronic urticaria on subjective well-being. It consists of 23 questions in 3 domains (symptoms, general impairment, difficulties and problems due to urticaria). Participants 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). An overall score is calculated and normalized to a scale of 1 to 100. | Baseline, 4, 12, 20, 28 and 36 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Angioedema Burdened Days by Study Phase (Observed Cases With Imputation) |  | Baseline, week 28; and the follow-up period (weeks 29-36) | 
| Mean Time Interval Between Successive Angioedema Episodes of the First 15 Episodes |  | Baseline to week 28 | 
| Change of Angioedema Activity Score (AAS) Total Week Sum Scores: Unadjusted Analysis and ANCOVA (Observed Cases With Imputation) | A cumulative activity score, evaluated in the screening period and throughout the study. The records each evening on a daily basis symptoms of itch and hives into a patient diary. min. score = 0 ; max. score= 100 | Baseline to week 28; and follow-up period (to week 36) | 
| Diameter: Acute Swelling Episodes Within the Screening Period (Week -2 to -1) | data points per group | week -2 to -1 | 
| Diameter: Acute Swelling Episodes at End of Treatment (Weeks 25 to 28) | data points per group | weeks 25 to 28 | 
| Diameter: Acute Swelling Episodes at End of Follow-up(Weeks 33 to 36) | data points per group | weeks 33 to 36 | 
| Shortness of Breath: Acute Swelling Episodes Within the Screening Period (Weeks -2 to -1) | data points per group | weeks -2 to -1 | 
| Shortness of Breath: Acute Swelling Episodes at End of Treatment Period (Weeks 25 to 28) | data points per group | weeks 25 to 28 | 
| Shortness of Breath: Acute Swelling Episodes at End of Follow-up Period (Weeks 33 to 36) | data points per group | weeks 33 to 36 | 
| Change of AE-Q2oL Scores From Baseline to Week 28: Unadjusted Analysis and ANCOVA (Observed Cases) | The AE-Q2oL is a questionnaire for patients suffering from angioedema. It consists of 29 questions relevant to angioedema and its specific impact on quality of life. Patients are asked to respond how much they are troubled be each problem on a 5-point Likert scale (1= does not apply to 5= very much). An overall score is calculated and a higher score indicates lower quality of life. A negative change score (week 28 score minus baseline score) indicates improvement. Each AE-QoL question has 5 answer options (scored 1-5), with lower and higher scores indicting less and more adverse impact, respectively. The total score is calculated, which is then transformed into a linear scale that ranges from 0 to 100, with a score of 100 indicating the worst possible impairment of HRQoL | baseline to week 28; and then follow-up to week 36 | 
| Rescue Medication During the Treatment Period |  | baseline to 28 weeks | 
| Days of Rescue Medication During the Treatment Period | data points per group | baseline to 28 weeks | 
| Days of Rescue Medication During the Follow-up Period | data points per group | weeks 33 to 36 | 
| Change of UAS7 Total Scores From Baseline to Week 28: Unadjusted Analysis and ANCOVA (Observed Cases) | The UAS7 is the sum of urticaria activity scores over a seven day period. The possible range of the weekly UAS7 score is 0-42. 0 means complete response and a better outcome and 42 means no response and a worse outcome. Complete UAS7 response is defined as UAS7=0. The UAS7 is the sum of the Hive Severity Score over seven days (HSS7) and the Itch Severity Score over seven days (ISS7) . The Hive Severity Score has a scale of 0 (none) to 3 (intense/severe). Complete hives response is defined as HSS7=0. The Itch Severity Score has a scale of 0 (None) to 3 (Severe (difficult to tolerate)). Complete itch response is defined as ISS7=0 | baseline to week 28; and then follow-up to week 36 | 
| Change of DLQI Scores From Baseline to Week 28: Unadjusted Analysis and ANCOVA (Observed Cases) | change in Dermatology Quality of Life Index scores The DLQI is a ten item general dermatology disability index designed to assess health-related quality of life in adult participants with skin diseases such as eczema, psoriasis, acne and viral worts. It is a self-administered questionnaire which includes domains of daily activity, leisure, personal relationships, symptoms and feelings, treatment and school/work activities. Each domain has 4 response categories ranging from 0 (not at all) to 3 (very much). Not relevant is a valid score also and is scored as 0. The DLQI total score is a sum of all 10 responses. Scores range from 0 to 30 with higher scores indicating greater health-related quality of life impairment. | baseline to week 28; and follow-up to week 36 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic spontanous urticaria, refractory CSU, Angioedema