A Study of Xolair (Omalizumab) in Patients With Chronic Idiopathic Urticaria (CIU) Who Remain Symptomatic With Antihistamine Treatment (H1)
- Conditions
- Chronic Idiopathic Urticaria
- Interventions
- Registration Number
- NCT00866788
- Lead Sponsor
- Genentech, Inc.
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 90
- CIU diagnosis > 3 months (by history)
- No underlying etiology clearly defined for urticaria (main manifestation cannot be physical urticaria)
- 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).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Omalizumab 75 mg H1 antihistamines 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.). Omalizumab 300 mg omalizumab 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. Omalizumab 300 mg H1 antihistamines 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. Omalizumab 300 mg Diphenhydramine 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. Omalizumab 600 mg H1 antihistamines 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. Placebo placebo 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. Placebo H1 antihistamines 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. Placebo Diphenhydramine 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. Omalizumab 75 mg omalizumab 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.). Omalizumab 75 mg Diphenhydramine 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.). Omalizumab 600 mg Diphenhydramine 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. Omalizumab 600 mg omalizumab 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. Placebo omalizumab 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.
- Primary Outcome Measures
Name Time Method Change in Urticaria Activity Score 7 (UAS7) From Baseline to Week 4 Baseline (based on the 7 days prior to randomization) and 4 weeks (Days 21-27) 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.
- Secondary Outcome Measures
Name Time Method Number of Participants With Immunogenicity 16 weeks Immunogenicity was measured by detection of anti-therapeutic antibodies (anti-omalizumab antibodies) using a fragment enzyme-linked immunosorbent assay (ELISA).
Area Under the Concentration-time Curve From Time of Dosing Extrapolated to Infinity (AUC-Inf) 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) 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.
Change in the Weekly Score for the Amount of Rescue Medication From Baseline to Week 4 Baseline (based on the 7 days prior to randomization) and 4 weeks (Days 21-27) 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.
Terminal Half-Life (t1/2) 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) 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.
Change in the Weekly Pruritus Score From Baseline to Week 4 Baseline (based on the 7 days prior to randomization) and 4 weeks (Days 21-27) 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.
Change in the Weekly Score for Number of Hives From Baseline to Week 4 Baseline (based on the 7 days prior to randomization) and 4 weeks (Days 21-27) 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.
Change in the Weekly Score for Sleep Interference From Baseline to Week 4 Baseline (based on the 7 days prior to randomization) and 4 weeks (Days 21-27) 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.
Number of Patients With Adverse Events by Severity 16 weeks overall (data reported separately for "up to 4 weeks" and "Weeks 5 to 16") 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.Time to Maximum Concentration (Tmax) 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) Tmax is the time to maximum concentration of omalizumab.
Maximum Observed Concentration (Cmax) 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) Cmax is the maximum (or peak) concentration of omalizumab in serum.