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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT01287117
First received: January 27, 2011
Last updated: November 4, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
Chronic Idiopathic Urticaria
Drug: Omalizumab
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase III, Multicenter, Randomized, Double-blind, Placebo-controlled, Dose-ranging Study to Evaluate the Efficacy and Safety of Xolair® (Omalizumab) in Patients With Chronic Idiopathic Urticaria (CIU)/Chronic Spontaneous Urticaria (CSU) Who Remain Symptomatic Despite Antihistamine Treatment (H1)

Resource links provided by NLM:


Further study details as provided by Genentech, Inc.:

Primary Outcome Measures:
  • Change From Baseline to Week 12 in the Weekly Itch Severity Score [ Time Frame: Baseline to Week 12 ] [ Designated as safety issue: No ]
    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 Outcome Measures:
  • Change From Baseline to Week 12 in the Urticaria Activity Score Over 7 Days (UAS7) [ Time Frame: Baseline to Week 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline to Week 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline to Week 12 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With a UAS7 Score ≤ 6 at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline to Week 12 ] [ Designated as safety issue: No ]
    The percentage of participants with an itch severity score at 12 Weeks at least 5 points lower than at Baseline.

  • Change From Baseline to Week 12 in the Weekly Size of the Largest Hive Score [ Time Frame: Baseline to Week 12 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in the Overall Dermatology Life Quality Index (DLQI) Score at Week 12 [ Time Frame: Baseline to Week 12 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Angioedema-free Days From Week 4 to Week 12 [ Time Frame: Week 4 to Week 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    A complete responder was defined as a participant with a UAS7 score = 0 at Week 12.


Enrollment: 319
Study Start Date: February 2011
Study Completion Date: October 2012
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Participants received placebo subcutaneously every 4 weeks during the 24 week treatment period.
Drug: Placebo
Placebo was supplied as a lyophilized, sterile powder in a single-use vial without study drug.
Experimental: Omalizumab 75 mg
Participants received omalizumab 75 mg subcutaneously every 4 weeks during the 24 week treatment period.
Drug: Omalizumab
Omalizumab was supplied as a lyophilized, sterile powder in a single-use vial.
Other Name: Xolair
Experimental: Omalizumab 150 mg
Participants received omalizumab 150 mg subcutaneously every 4 weeks during the 24 week treatment period.
Drug: Omalizumab
Omalizumab was supplied as a lyophilized, sterile powder in a single-use vial.
Other Name: Xolair
Experimental: Omalizumab 300 mg
Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 24 week treatment period.
Drug: Omalizumab
Omalizumab was supplied as a lyophilized, sterile powder in a single-use vial.
Other Name: Xolair

Detailed Description:

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

Ages Eligible for Study:   12 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01287117

  Show 66 Study Locations
Sponsors and Collaborators
Genentech, Inc.
Investigators
Study Director: Clinical Trials Genentech, Inc.
  More Information

No publications provided

Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT01287117     History of Changes
Other Study ID Numbers: Q4881g, GA00887
Study First Received: January 27, 2011
Results First Received: August 13, 2013
Last Updated: November 4, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Urticaria
Hypersensitivity
Hypersensitivity, Immediate
Immune System Diseases
Skin Diseases
Skin Diseases, Vascular
Histamine Antagonists
Histamine H1 Antagonists
Omalizumab
Anti-Allergic Agents
Anti-Asthmatic Agents
Histamine Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Respiratory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014