Treatment of Idiopathic Angioedema With Xolair as Add-on Therapy

Study Overview
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Brief Summary
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The overall hospitalizations for a diagnosis of angioedema doubled from the year 2000 to 2009. Although some of the cases represented hereditary angioedema or ace-inhibitor induced angioedema, the majority of episodes were idiopathic. Idiopathic Angioedema (IAE) can be life- threatening especially when affecting tissues within the respiratory tract. No clear guidelines exist for management of this important condition for clinicians. Current therapies typically include avoidance of potential triggers and use of medications either for prophylaxis or for acute events, such as antihistamines, corticosteroids, and epinephrine. There remains a critical need for therapeutic options to provide more effective prophylaxis.

Detailed Description
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This study is a randomized, double-blind, placebo-controlled, parallel group trial which will study the effects of omalizumab on patients with 2 or more episodes of Idiopathic Angioedema (IAE) in the past 6 months, despite current therapy. This study has three periods; screening, treatment, and follow-up. Subjects in the screening period will be consented and screened for eligibility criteria. 40 qualified individuals will enter the treatment period. Individuals will be randomized to either monthly subcutaneous administration of omalizumab 300mg (20 subjects) versus monthly placebo injection (20 subjects) in addition to their previously prescribed management plan for a total of 6 months. Individuals will then enter a follow-up period of 4 months. Study visits will occur monthly during the treatment period for update of clinical status and administration of omalizumab/placebo injection. After, the treatment period individuals will be seen twice for follow-up period. The entire study will consist of 10 study visits and will last approx. 10 months.

Official Title
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A Phase IV, Randomized, Double-Blind, Placebo-Controlled Exploratory Study of Xolair (Omalizumab) for Treatment of Idiopathic Angioedema in Patients Who Remain Symptomatic Despite Current Therapy

Conditions
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Idiopathic Angioedema

Intervention / Treatment
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* Drug: Omalizumab
* Drug: Placebos


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults or adolescents who are 18 years or older at the time of screening with physician diagnosis of idiopathic angioedema Minimum of two episodes of idiopathic angioedema in the past 6 months at the time of screening Management of idiopathic angioedema with a stable controller treatment plan for the prior 6 months Complement profile (C1 Esterase inhibitor panel) within normal reference values If a woman is of child-bearing potential, she must agree to a reliable form of birth control including: abstinence, oral contraceptives (birth control pills), Depo-provera, an intrauterine device (IUD), or double-barrier contraception (partner using condom and participant using diaphragm, contraceptive sponge or cervical cap, and spermicidal) Exclusion Criteria: Diagnosis of Hereditary Angioedema (HAE), Acquired Angioedema, or Ace-inhibitor associated angioedema, which are forms of angioedema with known mechanisms and alternate treatment options Chronic Urticaria (itching and/or hives) with or without Angioedema which are known mast cell mediated processes previously shown to be responsive to the use of omalizumab Previous usage of omalizumab in the last 3 months which can affect the patient-related outcomes and biomarker assessments if not washed out of the system Patients, who in the judgment of the investigator, have a history or condition that might compromise patient safety or compliance, interfere with evaluations, or preclude completion of the study

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo contains sodium chloride 0.9% and will be provided by Novartis. Placebo will be administered as a subcutaneous injection. | Drug: Placebos<br>* Placebo Group (Sodium Chloride 0.9%) two 1.2mL subcutaneous injections once monthly for 6 months.<br>|
| Active Comparator: Omalizumab<br>Omalizumab is a sterile, white, preservative-free, lyophilized powder, contained in a single-use vial that will be reconstituted with sterile water for injection (SWFI), USP, and administered as a subcutaneous injection. Each omalizumab vial contains 202.5 mg of omalizumab, 145.5 mg sucrose, 2.8 mg L-histidine hydrochloride monohydrate, 1.8 mg L-histidine, and 0.5 mg polysorbate 20. Each vial is designed to deliver 150 mg of omalizumab in 1.2 mL after reconstitution with 1.4 mL SWFI, USP. | Drug: Omalizumab<br>* Omalizumab 300mg subcutaneous injection once monthly for 6 months. Total dose will be divided into two 150mg/1.2mL injections.<br>* Other names: Xolair;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean 7-day Angioedema Activity Score (AAS7) | The AAS7 Score is a measure of the frequency and intensity of angioedema episodes. The total possible range of scores over 7 days is 0-15 (mean day sum score) where higher scores indicate increased angioedema activity. | baseline to end of treatment period at 6 months | 
| Presence of a 7-day Angioedema Activity Score (AAS7) Greater Than 0 Across All Treatment Visits | The AAS7 Score is a measure of the frequency and intensity of angioedema episodes. The total possible range of scores over 7 days is 0-15 (mean day sum score) where higher scores indicate increased angioedema activity. | across all visits during treatment period (up to 6 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Angioedema Quality of Life (AE-QoL) Questionnaire | The AE-QoL Questionnaire is a 17-item survey, the total possible range of scores is transformed to a scale of 1-100 where higher score indicate increased impairment. | baseline to end of treatment period at 6 months | 
| Mean Angioedema Quality of Life (AE-QoL) Questionnaire Across All Treatment Visits | The AE-QoL Questionnaire is a 17-item survey, the total possible range of scores is transformed to a scale of 1-100 where higher score indicate increased impairment. | across all visits during treatment period (up to 6 months) | 
| Mean Visual Analog Scale | The effect of treatment compared to placebo on the change in IAE severity from baseline to the end of the treatment period as recorded on a 0-100 visual analog scale. Lower numbers indicate increased severity. | baseline to end of treatment period at 6 months | 
| Presence of Visual Analog Scale Less Than 100 Across All Treatment Visits | The effect of treatment compared to placebo on the change in IAE severity from baseline to the end of the treatment period as recorded on a 0-100 visual analog scale. Lower numbers indicate increased severity. | across all visits during treatment period (up to 6 months) | 
| Mean Number of IAE Episodes 2 Weeks Prior to Randomization | Idiopathic angioedema (IAE) refers to episodes of angioedema without urticaria for which no explanation can be found despite a thorough investigation. Patients are sometimes referred to as having IAE while further investigations are being performed, and therefore this term does not necessarily represent a distinct condition, but rather a diagnostic challenge in which the pathway of swelling is yet to be determined. | baseline to end of treatment period at 6 months | 
| Number of IAE Events Across All Treatment Visits |  | across all visits during treatment period (up to 6 months) | 
| Change in Duration of IAE Episodes | Duration of IAE Episodes is participant reported for the 6 months prior to study (baseline) and again at the 6 month time point for the time on study. | baseline to end of treatment period at 6 months | 
| Number of Participants Who Visited Urgent Care or Emergency Room | Count of participants who visited urgent care or the emergency room is participant reported. The baseline measure is for the 6 months prior to study, at the 6 month time point for the time on study, and the 9 month time point for the previous 3 months on study. | baseline, end of treatment period at 6 months, follow up at 9 months | 
| Number of Participants Who Used Rescue Medication or Corticosteroids |  | baseline, end of treatment period at 6 months, follow up at 9 months | 
| Number of Times Rescue Medications Were Used During the Treatment Period |  | up to 26 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Angioedema, Idiopathic Angioedema, IAE