a study of the efficacy and safety of omalizumab (xolair) in patients with chronic idiopathic urticaria (ciu)/chronic spontaneous urticaria (csu) who remain symptomatic despite antihistamine (h1) treatment

Conditions: Chronic Idiopathic Urticaria

Summary: the study is a global phase iii, multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of omalizumab administered subcutaneously as an add-on therapy for the treatment of adolescent and adult patients aged 12-75 who have been diagnosed with refractory ciu and who remain symptomatic despite standard-dose h1 antihistamine treatment.

type i error rate control plan primary outcome measure in order to maintain an overall type i error rate of 0.05 (2-sided) across the 3 omalizumab dose levels, the testing of the primary outcome measure was conducted in the following hierarchical order. a p-value \< 0.05 is only considered statistically significant if statistical significance was claimed at the previous stage. * stage 1: omalizumab 300-mg group vs. placebo * stage 2: omalizumab 150-mg group vs. placebo * stage 3: omalizumab 75-mg group vs. placebo secondary outcome measures a hierarchical analysis of the following secondary outcome measures was performed for each dose found to be significant in the primary outcome measure. a p-value \< 0.05 is only considered statistically significant if statistical significance was claimed at the previous stage. * stage 1: change from baseline to week 12 in the urticaria activity score over 7 days (uas7) * stage 2: change from baseline to week 12 in the weekly number of hives score * stage 3: time to minimally important difference (mid) response in the weekly itch severity score by week 12 * stage 4: percentage of participants with a uas7 score ≤ 6 at week 12 * stage 5: percentage of weekly itch severity score mid responders at week 12 * stage 6: change from baseline to week 12 in the weekly size of the largest hive score * stage 7: change from baseline in the overall dermatology life quality index (dlqi) score at week 12 * stage 8: change from baseline in the overall dermatology life quality index (dlqi) score at week 12 * stage 9: percentage of complete responders (uas7 = 0) at week 12

Eligibility criteria:
inclusion criteria: * diagnosis of chronic idiopathic urticaria (ciu)/chronic spontaneous urticaria (csu) refractory to h1 antihistamines at the time of randomization. exclusion criteria: * treatment with an investigational agent within 30 days prior to screening. * weight \< 20 kg (44 lbs). * clearly defined underlying etiology for chronic urticarias other than ciu. * evidence of parasitic infection. * atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus, or other skin disease associated with itch. * previous treatment with omalizumab within a year prior to screening. * routine doses of the following medications within 30 days prior to screening: systemic or cutaneous (topical) corticosteroids (prescription or over the counter), hydroxychloroquine, methotrexate, cyclosporine, or cyclophosphamide. * intravenous (iv) immunoglobulin g (ivig), or plasmapheresis within 30 days prior to screening. * regular (daily/every other day) doxepin (oral) use within 6 weeks prior to screening. * any h2 antihistamine use within 7 days prior to screening. * any leukotriene receptor antagonist (ltra) (montelukast or zafirlukast) within 7 days prior to screening. * any h1 antihistamines at greater than approved doses within 3 days prior to screening. * patients with current malignancy, history of malignancy, or currently under work-up for suspected malignancy except non-melanoma skin cancer that has been treated or excised and is considered resolved. * hypersensitivity to omalizumab or any component of the formulation. * history of anaphylactic shock. * presence of clinically significant cardiovascular, neurological, psychiatric, metabolic, or other pathological conditions that could interfere with the interpretation of the study results and or compromise the safety of the patients. * evidence of current drug or alcohol abuse. * nursing women or women of childbearing potential, unless they meet the following definition of post-menopausal: 12 months of natural amenorrhea or 6 months of spontaneous amenorrhea with serum follicle-stimulating hormone (fsh) levels \> 40 miu/ml or 6 weeks post surgical bilateral oophorectomy (with or without hysterectomy) or hysterectomy or are using one or more of the following acceptable methods of contraception: surgical sterilization, hormonal contraception, and double-barrier methods.