A Phase III, Multicenter, Randomized, Double-blind, Dose-ranging, Placebo-controlled Study to Evaluate the Efficacy, Response Duration and Safety of Xolair (Omalizumab) in Patients With Chronic Idiopathic Urticaria (CIU)/Chronic Spontaneous Urticaria Who Remain Symptomatic Despite Antihistamine Treatment (H1)
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Genentech, Inc.
- Enrollment
- 323
- Primary Endpoint
- Change From Baseline in the Weekly Itch Severity Score at Week 12
Study Overview
Brief 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-dosed H1 antihistamine treatment.
Detailed Description
The trial incorporated a Type I error control plan, as follows:
The testing of the primary endpoint was conducted in the following hierarchical order. A p-value that is less than 0.05 can only be claimed statistically significant if statistical significance has been 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
A hierarchical analysis of the secondary endpoints was performed for each dose found to be significant in the primary endpoint. A p-value that is less than 0.05 can only be claimed statistically significant if statistical significance has been claimed at the previous stage.
- Stage 1: Change from baseline in Urticaria Activity Score (UAS7) at Week 12
- Stage 2: Change from baseline in the weekly number of hives score at Week 12
- Stage 3: Time to weekly itch severity score Minimally Important Difference (MID) response at Week 12
- Stage 4: Proportion of patients with UAS7 ≤ 6 at Week 12
- Stage 5: Proportion of weekly itch severity score MID Responders at Week 12
- Stage 6: Change from baseline in weekly size of the largest hive score at Week 12
- Stage 7: Change from baseline in overall Dermatology Life Quality Index (DLQI) score at Week 12
- Stage 8: Proportion of angioedema-free days from Week 4 to Week 12
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 12 Years to 75 Years (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Diagnosis of Chronic Idiopathic Urticaria (CIU)/Chronic Spontaneous Urticaria (CSU) CIU/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 milli-international units per milliliter (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.
Arms & Interventions
Placebo
Placebo subcutaneously (sc) every 4 weeks
Intervention: Placebo (Drug)
Placebo
Placebo subcutaneously (sc) every 4 weeks
Intervention: Omalizumab (Drug)
Omalizumab 75 mg
Omalizumab 75 mg sc every 4 weeks
Intervention: Omalizumab (Drug)
Omalizumab 150 mg
Omalizumab 150 mg sc every 4 weeks
Intervention: Omalizumab (Drug)
Omalizumab 300 mg
Omalizumab 300 mg sc every 4 weeks.
Intervention: Omalizumab (Drug)
Outcomes
Primary Outcomes
Change From Baseline in the Weekly Itch Severity Score at Week 12
Time Frame: Baseline, Week 12
The weekly itch severity score is the sum of the daily itch severity scores over 7 days and ranges from 0 to 21. The daily itch severity score is the average of the morning and evening scores on a scale of 0 (none) to 3 (severe). The Baseline weekly itch severity score is the sum of the daily itch severity scores over the 7 days prior to the first treatment. A higher itch severity score indicates more severe itching. A negative change score indicates improvement.
Secondary Outcomes
- Change From Baseline in the Weekly Size of the Largest Hive Score at Week 12(Baseline, Week 12)
- Change From Baseline in the Weekly Urticaria Activity Score (UAS7) at Week 12(Baseline, Week 12)
- Change From Baseline in the Weekly Number of Hives Score at Week 12(Baseline, Week 12)
- Percentage of Weekly Itch Severity Score MID Responders at Week 12(Baseline, Week 12)
- Percentage of Angioedema-free Days From Week 4 to Week 12(Week 4 to Week 12)
- Time to Minimally Important Difference (MID) Response in the Weekly Itch Severity Score by Week 12(by Week 12)
- Percentage of Participants With a UAS7 Less Than or Equal to 6 at Week 12(Week 12)
- Change From Baseline in the Overall Dermatology Life Quality Index (DLQI) at Week 12(Baseline, Week 12)