Mepolizumab for the Treatment of Chronic Spontaneous Urticaria

Study Overview
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Brief Summary
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This is an exploratory study designed to generate preliminary data in evaluating the efficacy of Nucala in the treatment of chronic spontaneous urticaria.

Detailed Description
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This is an open-label, single arm exploratory study of mepolizumab in the treatment of CSU. The primary endpoint will be the mean reduction in the seven day urticaria activity score (UAS7) before and after 10 weeks of treatment with mepolizumab. Secondary endpoints will be the mean reduction of the urticaria control test (UCT) score and the weekly itch severity score (ISS) before and after treatment. Enrollment examination will include a standardized history and examination, baseline UCT score, CBC with differential, serum IgE level, chronic urticaria index, IgE Fc receptor antibody functional assay, and a 4 mm punch biopsy of lesional skin to confirm the urticarial tissue reaction includes eosinophils and is not neutrophilic predominant. Patients will discontinue all anti-histamines and start cetirizine 10 mg PO BID which may be continued throughout the study duration. Patients will be provided with a log book to track daily urticaria signs and symptoms in a standardized manner for UAS scoring. At week 0 (enrollment visit +7 days), baseline UAS7 and ISS score will be assessed and skin biopsy results reviewed. Patients with a confirmatory skin biopsy will receive 200 mg SC of mepolizumab at week 0,2,4,6,and 8. UAS-7 and weekly ISS score will be calculated at week 0, 4, 8, and 10. UCT scoring will be calculated at week 0 and at week 10. Repeat CBC with differential, serum IgE level, and measures of basophil serum activation (chronic urticaria index, IgE FC Receptor antibody functional assay) will be assessed at week 10. Attached to this document is a protocol summary.

Official Title
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Mepolizumab for the Treatment of Chronic Spontaneous Urticaria: An Open-label, Single-arm, Exploratory Study

Conditions
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Chronic Spontaneous Urticaria

Intervention / Treatment
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* Drug: Nucala


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients 18 years or older. Clinical and/or histopathological diagnosis of conventional CSU Unresponsive to oral antihistamine therapy Good general health as confirmed by medical history Patients who are willing and capable of cooperating to the extent and degree required by the protocol; and Patients who read and sign an approved informed consent for this study Exclusion Criteria: Vulnerable study population Pregnant or nursing women Women planning a pregnancy within the study period Current or previous Xolair use Biopsy proven neutrophilic rich urticaria Known history of adverse reaction to Nucala Severe asthma requiring high-dose inhaled or systemic corticosteroids

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Interventional Model Description: Mepolizumab for the treatment of chronic spontaneous urticaria
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Arm<br>This is an open-label pilot investigation and all study participants are assigned to active treatment. There is no placebo arm in this study. | Drug: Nucala<br>* All study participants will receive Nucala (2) 100mg SQ injections administered at two different anatomical sites at week zero, 2,4,6, and 8 for a total of 5 doses.<br>* Other names: Mepolizumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean UAS score 7 | Study participants will document their CSU symptoms using a diary,daily scoring for a) the number of wheals [none (=0 points), <10 (=1 point), 10-50 (=2 points), or >50 per day (=3 points)], and b) the intensity of pruritus [none (=0 points), mild (=1 point), moderate (=2 points), severe (=3 points)]. The daily UAS score is summed over a week to calculate the UAS7 score (range: 0-42). | Study participants will document their CSU symptoms using a diary during the 10 week study period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean reduction in ISS and UCT | The weekly itch severity score is calculated using the pruritus score of the daily UAS score summed over a week (range: 0-21). The urticaria control test (UCT) is a more recently developed and validated outcome instrument to retrospectively assess urticaria control. Each UCT item has 5 answer options scored 0-4 with low points indicating high disease activity and low disease control. The minimum and maximum UCT scores are 0-16 with 16 points indicating complete disease control. | 10 weeks of treatment with mepolizumab |