A Safety Study of Xolair (Omalizumab) in Patients With Chronic Idiopathic Urticaria (CIU) Who Remain Symptomatic Despite Treatment With H1 Antihistamines, H2 Blockers, and/or Leukotriene Receptor Antagonists

Phase 3

Completed

• Conditions: Chronic Idiopathic Urticaria
• Interventions: Drug: Placebo; Drug: Omalizumab; Drug: H1 antihistamine, H2 antihistamine, leukotriene receptor antagonist; Drug: Diphenhydramine

• Registration Number: NCT01264939
• Lead Sponsor: Genentech, Inc.

Brief Summary

The study is a global Phase III, multicenter, randomized, double-blind, placebo controlled, parallel-group study to evaluate the safety and efficacy 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 chronic idiopathic urticaria (CIU) who remain symptomatic despite standard-dosed H1 antihistamine treatment (including doses up to 4 times above the approved dose level), H2 blockers, and/or leukotriene receptor antagonists (LTRA).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2010-12-20
• Study First Submitted QC: 2010-12-20
• Study First Posted: 2010-12-22
• Study Start: 2011-02
• Primary Completion: 2012-11
• Study Completion: 2012-11
• Status Verified: 2013-09
• Results First Submitted: 2013-09-23
• Results First Submitted QC: 2013-09-23
• Last Update Submitted: 2013-09-23
• Results First Posted: 2013-11-26
• Last Update Posted: 2013-11-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 336

Inclusion Criteria

• Diagnosis of chronic idiopathic urticaria (CIU) refractory to H1 antihistamines, H2 blockers, and/or leukotriene receptor antagonists (LTRA) at the time of randomization.

  • The presence of itch and hives for > 6 consecutive weeks at any time prior to enrollment despite current use of H1 antihistamine (up to 4 times the approved dosage), H2 blocker, and/or LTRA treatment during this time.
  • Urticaria activity score over 7 days (UAS7) score (range 0-42) ≥ 16 and itch component of UAS7 (range 0-21) ≥ 8 during 7 days prior to randomization (Week 0).
  • In-clinic UAS ≥ 4 on at least one of the screening visit days (Day -14, Day -7, or Day 1).

• For women of childbearing potential, agreement to use an acceptable form of contraception and to continue its use for the duration of the study.

Exclusion Criteria

• Treatment with an investigational agent within 30 days prior to screening.
• Weight less than 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.
• 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Participants received placebo subcutaneously every 4 weeks during the 24 week treatment period.
Placebo	H1 antihistamine, H2 antihistamine, leukotriene receptor antagonist	Participants received placebo subcutaneously every 4 weeks during the 24 week treatment period.
Omalizumab 300 mg	H1 antihistamine, H2 antihistamine, leukotriene receptor antagonist	Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 24 week treatment period.
Placebo	Diphenhydramine	Participants received placebo subcutaneously every 4 weeks during the 24 week treatment period.
Omalizumab 300 mg	Diphenhydramine	Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 24 week treatment period.
Omalizumab 300 mg	Omalizumab	Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 24 week treatment period.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Adverse Events	Baseline to the end of study (up to 40 weeks)	The percentage of participants with serious adverse events and other adverse events is summarized by MedDRA preferred terms and organ classes in the Reported Adverse Events section below.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With a UAS7 Score ≤ 6 at Week 12	Week 12	The UAS7 is the sum of the daily urticarial activity scores over 7 days and ranges from 0 to 42. The daily urticarial activity score is the average of the morning and evening urticarial activity scores and ranges from 0 to 6. The urticarial activity score is the sum of ratings on a scale of 0 to 3 (0=none to 3=intense/severe) for (1) the number of wheals (hives) and (2) itch intensity over the previous 12 hours, ranges from 0 to 6, and is measured twice daily (morning and evening). The Baseline score is the sum of the daily urticarial activity scores over the 7 days prior to the first treatment. A higher urticarial activity score indicates more urticaria activity.
Percentage of Weekly Itch Severity Score MID Responders at Week 12	Baseline to Week 12	The percentage of participants with an itch severity score at 12 Weeks at least 5 points lower than at Baseline. 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.
Change From Baseline in the Overall Dermatology Life Quality Index (DLQI) Score at Week 12	Baseline to Week 12	The DLQI is a 10-item dermatology-specific health-related quality of life measure. Patients rated their dermatology symptoms as well as the impact of their skin condition on various aspects of their lives on a scale of 0 (Not at all) to 3 (Very much). The overall DLQI is the sum of the responses to the 10 items and ranges from 0 to 30. A lower score indicates a better quality of life. A negative change score indicates improvement.
Change From Baseline to Week 12 in the Weekly Itch Severity Score	Baseline to 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.
Change From Baseline to Week 12 in the Urticaria Activity Score Over 7 Days (UAS7)	Baseline to Week 12	The UAS7 is the sum of the daily urticarial activity scores over 7 days and ranges from 0 to 42. The daily urticarial activity score is the average of the morning and evening urticarial activity scores and ranges from 0 to 6. The urticarial activity score is the sum of ratings on a scale of 0 to 3 (0=none to 3=intense/severe) for (1) the number of wheals (hives) and (2) itch intensity over the previous 12 hours, ranges from 0 to 6, and is measured twice daily (morning and evening). The Baseline score is the sum of the daily urticarial activity scores over the 7 days prior to the first treatment. A higher urticarial activity score indicates more urticaria activity. A negative change score indicates improvement.
Change From Baseline to Week 12 in the Weekly Number of Hives Score	Baseline to Week 12	The weekly hives score is the sum of the daily hives scores over 7 days and ranges from 0 to 21. The number of hives is measured twice daily (morning and evening) on a scale of 0 (none) to 3 (\> 12 hives per 12 hours). The daily hives score is the average of the morning and evening scores. The Baseline score is the sum of the daily hives scores over the 7 days prior to the first treatment. A higher score indicates more hives. A negative change score indicates improvement.
Time to Minimally Important Difference (MID) Response in the Weekly Itch Severity Score by Week 12	Baseline to Week 12	The time to the MID response is the number of weeks from the start of treatment (Baseline) until the time point at which the first MID response occurs. The MID response is defined as a reduction ≥ 5 points from Baseline in the weekly itch severity score. 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.
Change From Baseline to Week 12 in the Weekly Size of the Largest Hive Score	Baseline to Week 12	The weekly size of the largest hive score is the sum of the daily size of the largest hive scores over 7 days and ranges from 0 to 21. The daily size of the largest hive score is assessed twice daily (morning and evening) on a scale of 0 (none) to 3 (\> 2.5 cm). The daily size of the largest hive score is the average of the morning and evening scores. The Baseline weekly size of the largest hive score is calculated over the 7 days prior to the first treatment. A higher score indicates larger hives. A negative change score indicates a reduction in hive size.
Percentage of Angioedema-free Days From Week 4 to Week 12	Week 4 to Week 12	The percentage of angioedema-free days from Weeks 4 to 12 was defined as the number of days for which a patient responded "No" to the angioedema question in the daily diary divided by the total number of days with a non-missing diary entry, starting at the Week 4 visit and ending the day prior to the Week 12 visit.
Percentage of Complete Responders (UAS7 = 0) at Week 12	Week 12	A complete responder was defined as a participant with a UAS7 score = 0 at Week 12. The UAS7 is the sum of the daily urticarial activity scores over 7 days and ranges from 0 to 42. The daily urticarial activity score is the average of the morning and evening urticarial activity scores and ranges from 0 to 6. The urticarial activity score is the sum of ratings on a scale of 0 to 3 (0=none to 3=intense/severe) for (1) the number of wheals (hives) and (2) itch intensity over the previous 12 hours, ranges from 0 to 6, and is measured twice daily (morning and evening). The Baseline score is the sum of the daily urticarial activity scores over the 7 days prior to the first treatment. A higher urticarial activity score indicates more urticaria activity.