Extending Omalizumab Treatment Intervals in Patients With Chronic Spontaneous Urticaria

Study Overview
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Brief Summary
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This study is a multicentre, randomized, open-label, non-inferiority clinical trial. The purpose and aim of this study is to investigate if patients with well controlled (UCT score score ≥ 12) chronic spontaneous urticaria (CSU) on omalizumab 300 mg every four weeks can extend treatment intervals and maintain disease control.

Detailed Description
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Newly referred patients with CSU who are well-treated (UCT score ≥ 12) 12 weeks after initiating standard treatment with omalizumab 300 mg every four weeks, are randomized into two treatment arms.The first arm will continue standard treatment with omalizumab 300 mg every four weeks for 24 weeks. The second arm will receive treatment in an extended interval of omalizumab 300 mg every six weeks for 24 weeks.

Official Title
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Extending Omalizumab Treatment Intervals in Patients With Chronic Spontaneous Urticaria (EXOTIC Trial): a Multicentre, Randomized, Open-label, Non-inferiority Trial

Conditions
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Chronic Spontaneous Urticaria, Chronic Urticaria, Idiopathic

Intervention / Treatment
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* Drug: omalizumab 300 mg every four weeks
* Drug: omalizumab 300 mg every six weeks


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of CSU according to the EAACI/GA2LEN/EDF/WAO guidelines Age ≥ 18 years Urticaria Control Test (UCT) score ≥ 12 at week 12 after initiating treatment with 300 mg of omalizumab every four weeks. Omalizumab-naïve prior to initiating treatment. Background treatment with four antihistamines daily. Type I CSU (negative basophil histamine release assay - BHRA). Identified as a candidate for omalizumab treatment according to Danish practice. Exclusion Criteria: Pregnant or breastfeeding women Planned pregnancy within the next 6 months. Body mass index (BMI) ≥ 100 kilograms Presence of any other active skin disease or condition that may interfere with the assessment of CSU, such as atopic dermatitis, bullous pemphigoid, senile pruritus, or psoriasis. Use of immunosuppressive drugs, such as prednisolone, azathioprine, methotrexate, or cyclosporine. Predominantly experiencing symptoms from chronic inducible urticaria (CIndU). Positive basophil histamine release assay (BHRA). Inability to complete the study or comply with study procedures.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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
Interventional Model Description: Multicenter, randomized, open-label, non-inferiority trial.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: omalizumab 300 mg every six weeks<br>20 subjects are randomized to receive omalizumab 300 mg every six weeks from week 12 to week 36. | Drug: omalizumab 300 mg every six weeks<br>* Treatment in an extended interval of omalizumab 300 mg every six weeks from week 12 to week 36. Both arms are treated with omalizumab 300 mg from week 0 to week 12.<br>* Other names: Extended treatment;|
| Active Comparator: omalizumab 300 mg every four weeks<br>20 subjects are randomized to receive omalizumab 300 mg every four weeks from week 12 to week 36. | Drug: omalizumab 300 mg every four weeks<br>* Continue standard treatment with omalizumab 300 mg every four weeks from week 12 to week 36. Both arms are treated with omalizumab 300 mg from week 0 to week 12.<br>* Other names: Standard treatment;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute difference in average Urticaria Control Test (UCT) score at week 36 | The Urticaria Control Test (UCT) is a retrospective questionnaire that gathers information regarding the past 4 weeks. It consists of four questions, each with four possible answer options. A score ranging from 0 to 4 is assigned to each answer option. Consequently, the UCT score ranges from 0 to 16, with higher scores indicating lower control of the disease. A UCT score of 12 or higher suggests well-controlled urticaria, while a score of 16 indicates complete control. | Through study completion, an average of 36 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute difference in average Urticaria Control Test (UCT) score at week 24 | The Urticaria Control Test (UCT) is a retrospective questionnaire that gathers information regarding the past 4 weeks. It consists of four questions, each with four possible answer options. A score ranging from 0 to 4 is assigned to each answer option. Consequently, the UCT score ranges from 0 to 16, with higher scores indicating lower control of the disease. A UCT score of 12 or higher suggests well-controlled urticaria, while a score of 16 indicates complete control. | Through study completion, an average of 36 weeks | 
| Proportion of well-controlled patients (UCT score ≥ 12) at week 24 and 36 | The Urticaria Control Test (UCT) is a retrospective questionnaire that gathers information regarding the past 4 weeks. It consists of four questions, each with four possible answer options. A score ranging from 0 to 4 is assigned to each answer option. Consequently, the UCT score ranges from 0 to 16, with higher scores indicating lower control of the disease. A UCT score of 12 or higher suggests well-controlled urticaria, while a score of 16 indicates complete control. | Through study completion, an average of 36 weeks | 
| Proportion of completely controlled patients (UCT score = 16) at week 24 and 36 | The Urticaria Control Test (UCT) is a retrospective questionnaire that gathers information regarding the past 4 weeks. It consists of four questions, each with four possible answer options. A score ranging from 0 to 4 is assigned to each answer option. Consequently, the UCT score ranges from 0 to 16, with higher scores indicating lower control of the disease. A UCT score of 12 or higher suggests well-controlled urticaria, while a score of 16 indicates complete control. | Through study completion, an average of 36 weeks | 
| Difference in absolute UCT score measured as area under the curve (AUC) | The Urticaria Control Test (UCT) is a retrospective questionnaire that gathers information regarding the past 4 weeks. It consists of four questions, each with four possible answer options. A score ranging from 0 to 4 is assigned to each answer option. Consequently, the UCT score ranges from 0 to 16, with higher scores indicating lower control of the disease. A UCT score of 12 or higher suggests well-controlled urticaria, while a score of 16 indicates complete control. | Through study completion, an average of 36 weeks | 
| Absolute difference in average weekly urticaria activity score (UAS7) at week 24 and 36 | The Urticaria Activity Score (UAS) is a score recorded in a diary that assesses the severity of wheals and intensity of pruritus experienced within a 24-hour period. The total UAS score can range from 0 to 6. The UAS7 is calculated by summing the daily UAS scores over the past week. The UAS7 score ranges from 0 to 42, with higher scores indicating greater disease activity. A UAS7 score of less than 7 suggests well-controlled urticaria, while a score of 0 indicates complete control. | Through study completion, an average of 36 weeks | 
| Proportion of well-controlled patients (UAS7 score < 7) at week 24 and 36 | The Urticaria Activity Score (UAS) is a score recorded in a diary that assesses the severity of wheals and intensity of pruritus experienced within a 24-hour period. The total UAS score can range from 0 to 6. The UAS7 is calculated by summing the daily UAS scores over the past week. The UAS7 score ranges from 0 to 42, with higher scores indicating greater disease activity. A UAS7 score of less than 7 suggests well-controlled urticaria, while a score of 0 indicates complete control. | Through study completion, an average of 36 weeks | 
| Proportion of completely controlled patients (UAS7 score = 0) at week 24 and 36 | The Urticaria Activity Score (UAS) is a score recorded in a diary that assesses the severity of wheals and intensity of pruritus experienced within a 24-hour period. The total UAS score can range from 0 to 6. The UAS7 is calculated by summing the daily UAS scores over the past week. The UAS7 score ranges from 0 to 42, with higher scores indicating greater disease activity. A UAS7 score of less than 7 suggests well-controlled urticaria, while a score of 0 indicates complete control. | Through study completion, an average of 36 weeks | 
| Differences in average Chronic Urticaria Quality of Life (CU-QoL) at week 24 and 36 | The Chronic Urticaria Quality of Life Questionnaire (Cu-QoL) is a retrospective questionnaire that gathers information regarding the past 2 weeks. The Cu-QoL consists of 23 questions, each scored on a scale from 1 (indicating no complaints) to 5 (indicating many complaints). Higher scores on the Cu-QoL reflect a lower quality of life. | Through study completion, an average of 36 weeks | 
| Differences in average dermatology life quality index (DLQI) at week 24 and 36 | The Dermatology Life Quality Index (DLQI) is a validated, self-administered questionnaire consisting of 10 items. It measures the impact of skin disease on patients' quality of life based on their recall of experiences over the past week. The questionnaire covers various domains, including symptoms, feelings, daily activities, social interactions, leisure activities, work or studying, personal relationships, and treatment. Each question is scored on a scale of 0 to 3, resulting in a total score range from 0 (indicating no impact of skin disease on quality of life) to 30 (indicating the maximum impact on quality of life). | Through study completion, an average of 36 weeks | 
| Proportion of patients in the two treatment arms who experience flares | Flares refer to the exacerbation of symptoms that prompt patients to reach out to their healthcare provider and/or request intensified treatment. | Through study completion, an average of 36 weeks | 
| Adverse event (AEs) and serious advese events (SAEs) | Adverse events (AEs) encompass any unfavorable and/or unintended signs, incidents, symptoms, or diseases associated with omalizumab. This also includes laboratory results falling outside the reference range, although only laboratory results deemed clinically relevant will be examined. Any AEs occurring from the first administration of the trial medication until 8 days after the last administration of the trial medicine will be documented. Serious adverse events (SAEs) are defined as AEs or adverse reactions that lead to death, are life-threatening, require hospitalization or prolongation of existing hospitalization, result in persistent or significant disability or incapacity, or involve a congenital anomaly or birth defect. | Through study completion, an average of 36 weeks |