A Study of Xolair (Omalizumab) in Patients With Chronic Idiopathic Urticaria (CIU) Who Remain Symptomatic With Antihistamine Treatment (H1)

Study Overview
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Brief Summary
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The study is a Phase II, dose-ranging, multicenter, randomized, double-blind, placebo-controlled, parallel-group study of the efficacy and safety of a single subcutaneously administered omalizumab dose as add-on therapy for the treatment of adolescent and adult patients 12-75 years old who have been diagnosed with CIU and remain symptomatic despite treatment with therapeutic doses of an H1 antihistamine. The study will enroll approximately 76 patients at approximately 45 study centers in the United States and Germany.

Official Title
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A Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled Dose-Ranging Study of Xolair (Omalizumab) in Patients With Chronic Idiopathic Urticaria (CIU) Who Remain Symptomatic With Antihistamine Treatment (H1)

Conditions
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Chronic Idiopathic Urticaria

Intervention / Treatment
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* Drug: omalizumab
* Drug: placebo
* Drug: H1 antihistamines
* Drug: Diphenhydramine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: CIU diagnosis > 3 months (by history) No underlying etiology clearly defined for urticaria (main manifestation cannot be physical urticaria) Exclusion Criteria: Pregnant, breastfeeding, or women not taking contraception Patients < 40kg Treatment with any investigational agent within 30 days of screening Recent history of drug or alcohol abuse Atopic dermatitis or other skin disease associated with pruritus Clinically relevant major systemic disease (making interpretation of the study results difficult) Previously treated with omalizumab (< 12 months since last injection) Patients may not take during treatment period or have been taking within the past 3 months any of the following medications/treatments: regular (daily/every other day) hydroxychloroquine, methotrexate, cyclosporine, cyclophosphamide, IVIG, or plasmapheresis Patients may not have been taking doxepin within the past 6 weeks regular (daily/every other day).

Ages Eligible for Study
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Minimum Age: 12 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: Omalizumab 75 mg<br>Omalizumab (Xolair) was administered subcutaneously on Day 0 of the study. Participants remained on stable doses of their pre-allocation Chronic Idiopathic Urticaria (CIU) H1 antihistamine treatment throughout the study, and were provided diphenhydramine as rescue medication for pruritus relief on an as-needed basis.). | Drug: omalizumab<br>* Administered by subcutaneous injection<br>* Other names: Xolair;Drug: H1 antihistamines<br>* Patients received one of the following: Cetirizine 10 mg once per day (QD), Levocetirizine dihydrochloride 5 mg QD, Fexofenadine 60 mg twice per day or 180 mg QD, Loratadine 10 mg QD or Desloratadine 5 mg QD<br>Drug: Diphenhydramine<br>* Diphenhydramine was provided and used on an as-needed basis (25 mg per dose)<br>|
| Experimental: Omalizumab 300 mg<br>Omalizumab (Xolair) was administered subcutaneously on Day 0 of the study. Participants remained on stable doses of their pre-allocation Chronic Idiopathic Urticaria (CIU) H1 antihistamine treatment throughout the study, and were provided diphenhydramine as rescue medication for pruritus relief on an as-needed basis. | Drug: omalizumab<br>* Administered by subcutaneous injection<br>* Other names: Xolair;Drug: H1 antihistamines<br>* Patients received one of the following: Cetirizine 10 mg once per day (QD), Levocetirizine dihydrochloride 5 mg QD, Fexofenadine 60 mg twice per day or 180 mg QD, Loratadine 10 mg QD or Desloratadine 5 mg QD<br>Drug: Diphenhydramine<br>* Diphenhydramine was provided and used on an as-needed basis (25 mg per dose)<br>|
| Experimental: Omalizumab 600 mg<br>Omalizumab (Xolair) was administered subcutaneously on Day 0 of the study. Participants remained on stable doses of their pre-allocation Chronic Idiopathic Urticaria (CIU) H1 antihistamine treatment throughout the study, and were provided diphenhydramine as rescue medication for pruritus relief on an as-needed basis. | Drug: omalizumab<br>* Administered by subcutaneous injection<br>* Other names: Xolair;Drug: H1 antihistamines<br>* Patients received one of the following: Cetirizine 10 mg once per day (QD), Levocetirizine dihydrochloride 5 mg QD, Fexofenadine 60 mg twice per day or 180 mg QD, Loratadine 10 mg QD or Desloratadine 5 mg QD<br>Drug: Diphenhydramine<br>* Diphenhydramine was provided and used on an as-needed basis (25 mg per dose)<br>|
| Placebo Comparator: Placebo<br>Participants received a single subcutaneous placebo injection on Day 0 of the study. Participants remained on stable doses of their pre-allocation Chronic Idiopathic Urticaria CIU) H1 antihistamine treatment throughout the study, and were provided diphenhydramine as rescue medication for pruritus relief on an as-needed basis. | Drug: omalizumab<br>* Administered by subcutaneous injection<br>* Other names: Xolair;Drug: placebo<br>* Participants received a single subcutaneous placebo injection on Day 0 of the study.<br>Drug: H1 antihistamines<br>* Patients received one of the following: Cetirizine 10 mg once per day (QD), Levocetirizine dihydrochloride 5 mg QD, Fexofenadine 60 mg twice per day or 180 mg QD, Loratadine 10 mg QD or Desloratadine 5 mg QD<br>Drug: Diphenhydramine<br>* Diphenhydramine was provided and used on an as-needed basis (25 mg per dose)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Urticaria Activity Score 7 (UAS7) From Baseline to Week 4 | The UAS is a composite diary-recorded score, which is the sum of the numeric severity intensity ratings (0 = none to 3 = intense) for 1) the number of wheals (hives) and 2) the intensity of the pruritus (itch). The UAS7 is the sum of the daily average UAS (morning and evening values) for 7 days. The maximum UAS7 score is 42. | Baseline (based on the 7 days prior to randomization) and 4 weeks (Days 21-27) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Weekly Pruritus Score From Baseline to Week 4 | The pruritus (itch) score was recorded by participants twice daily (morning and evening) based on the severity of itch over the last 12 hours, using a scale from 0 (none) to 3 (severe). The weekly pruritus score was the sum of average daily pruritus scores over the previous 7 days. The range of the weekly score is 0-21. | Baseline (based on the 7 days prior to randomization) and 4 weeks (Days 21-27) | 
| Change in the Weekly Score for Number of Hives From Baseline to Week 4 | The number of hives was recorded by participants twice daily (morning and evening) using a scale from 0 (no hives) to 3 (more than 12 hives). The weekly score of number of hives was the sum of the average daily scores over the previous 7 days, and ranged from 0 to 21. | Baseline (based on the 7 days prior to randomization) and 4 weeks (Days 21-27) | 
| Change in the Weekly Score for Sleep Interference From Baseline to Week 4 | The extent to which hives or itch interfered with participants' sleep was recorded once daily in the patient diary using a scale from 0 (no interference) to 3 (substantial interference, waking often). The weekly score of sleep interference was the sum of the daily scores over the previous 7 days, and ranged from 0 to 21. | Baseline (based on the 7 days prior to randomization) and 4 weeks (Days 21-27) | 
| Change in the Weekly Score for the Amount of Rescue Medication From Baseline to Week 4 | Diphenhydramine 25mg was provided and used on an as-needed basis (maximum 3 times/day) as rescue medication. The weekly score for the amount of rescue medication is the sum of the daily scores for the amount of rescue medication used at each day in the week, and ranged from 0 to 21. | Baseline (based on the 7 days prior to randomization) and 4 weeks (Days 21-27) | 
| Number of Patients With Adverse Events by Severity | The severity (i.e. intensity) of each Adverse Event (AE) was graded according to the following scale: Mild: Symptoms causing no or minimal interference with usual social and functional activities. Moderate: Symptoms causing greater than minimal interference with usual social and functional activities. Severe: Symptoms causing inability to perform usual social and functional activities. Additional AE data is provided in the AE section below. The terms severe and serious are not synonymous. Severity refers to the intensity of an AE. A Serious AE is defined below. | 16 weeks overall (data reported separately for up to 4 weeks and Weeks 5 to 16) | 
| Number of Participants With Immunogenicity | Immunogenicity was measured by detection of anti-therapeutic antibodies (anti-omalizumab antibodies) using a fragment enzyme-linked immunosorbent assay (ELISA). | 16 weeks | 
| Maximum Observed Concentration (Cmax) of Omalizumab | Cmax is the maximum (or peak) concentration of omalizumab in serum. | Pre-dose and 2 hours post-dose on Days 0 and 3 of Week 0, Weeks 1, 2, 3, 4, 8, 12, 16 or early termination (up to Week 16) | 
| Time to Maximum Concentration (Tmax) of Omalizumab | Tmax is the time to maximum concentration of omalizumab. | Pre-dose and 2 hours post-dose on Days 0 and 3 of Week 0, Weeks 1, 2, 3, 4, 8, 12, 16 or early termination (up to Week 16) | 
| Area Under the Concentration-time Curve From Time of Dosing Extrapolated to Infinity (AUC-Inf) | AUCinf is the area under the concentration-time curve from time of dosing extrapolated to infinity. AUCinf was measured in microgram times day per milliliter (µg*day/mL). Only participants having complete profiles and completed the study were included in the analysis. | Pre-dose and 2 hours post-dose on Days 0 and 3 of Week 0, Weeks 1, 2, 3, 4, 8, 12, 16 or early termination (up to Week 16) | 
| Terminal Half-Life (t1/2) of Omalizumab | Terminal Half-Life (t1/2) is the time required for the serum concentration of omalizumab to decrease by half in the final stage of its elimination. | Pre-dose and 2 hours post-dose on Days 0 and 3 of Week 0, Weeks 1, 2, 3, 4, 8, 12, 16 or early termination (up to Week 16) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Xolair, CIU