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

November 4, 2013 updated by: Genentech, Inc.

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)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Study Type

Interventional

Enrollment (Actual)

319

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • København, Denmark, 2400
      • Odense, Denmark, 5000
  • France
      • Bordeaux, France, 33000
      • Marseille, France, 13385
      • Reims, France, 51092
  • Germany
      • Berlin, Germany, 10117
      • Berlin, Germany, 10249
      • Berlin, Germany, D-13585
      • Dresden, Germany, D-01062
      • Freiburg, Germany, 79098
      • Heidelberg, Germany, 69115
      • Muenchen, Germany, 80337
      • Muenster, Germany, 48149
  • Italy
      • Perugia, Italy, 06159
      • Roma, Italy, 00167
      • Terni, Italy, 05100
  • Poland
      • Krakow, Poland, 31-531
      • Lodz, Poland, 90-153
      • Lublin, Poland, 20-718
      • Wroclaw, Poland, 51-124
  • Spain
      • Barcelona, Spain, 08003
      • Barcelona, Spain, 08041
      • Pamplona, Spain, 31003
  • Turkey
      • Ankara, Turkey, 06500
      • Bursa, Turkey, 16059
      • Istanbul, Turkey, 35100
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35209
    • California
      • Huntington Beach, California, United States, 92647
      • Long Beach, California, United States, 90808
      • Los Angeles, California, United States, 90027
      • Palmdale, California, United States, 93551
      • Sacramento, California, United States, 95817
      • San Jose, California, United States, 95117-1840
      • Studio City, California, United States, 91607
    • Colorado
      • Centennial, Colorado, United States, 80112
    • District of Columbia
      • Washington, District of Columbia, United States, 20037
    • Florida
      • Coral Gables, Florida, United States, 33134
      • Sarasota, Florida, United States, 34233
      • Tallahassee, Florida, United States, 32308
    • Georgia
      • Columbus, Georgia, United States, 31904
    • Illinois
      • Springfield, Illinois, United States, 62703
    • Indiana
      • Indianapolis, Indiana, United States, 46208
    • Massachusetts
      • Baltimore, Massachusetts, United States, 21224
      • Boston, Massachusetts, United States, 02114
      • Burlington, Massachusetts, United States, 01805
    • Missouri
      • St Louis, Missouri, United States, 63141
    • New Jersey
      • Edison, New Jersey, United States, 08820
      • Skillman, New Jersey, United States, 08558
    • New York
      • Bronx, New York, United States, 10465
      • Staten Island, New York, United States, 10304
    • North Carolina
      • Durham, North Carolina, United States, 27710
    • Ohio
      • Columbus, Ohio, United States, 43235
      • Toledo, Ohio, United States, 43623
    • Oklahoma
      • Tulsa, Oklahoma, United States, 74136
    • Oregon
      • Portland, Oregon, United States, 97210
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15212
      • Upland, Pennsylvania, United States, 19013
    • South Carolina
      • Charleston, South Carolina, United States, 29406
    • Texas
      • Fort Worth, Texas, United States, 76123
      • Houston, Texas, United States, 77054
      • Waco, Texas, United States, 76712
    • Utah
      • Salt Lake City, Utah, United States, 84107
      • Sandy, Utah, United States, 84070
    • Virginia
      • Springfield, Virginia, United States, 22152
    • Wisconsin
      • Lacrosse, Wisconsin, United States, 54601
      • Madison, Wisconsin, United States, 53792

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years to 75 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 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 Names:
  • Xolair
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 Names:
  • 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 Names:
  • Xolair

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline to Week 12 in the Weekly Itch Severity Score
Time Frame: 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.
Baseline to Week 12

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline to Week 12 in the Urticaria Activity Score Over 7 Days (UAS7)
Time Frame: 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.
Baseline to Week 12
Change From Baseline to Week 12 in the Weekly Number of Hives Score
Time Frame: 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.
Baseline to Week 12
Percentage of Participants With a UAS7 Score ≤ 6 at Week 12
Time Frame: 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.
Week 12
Change From Baseline to Week 12 in the Weekly Size of the Largest Hive Score
Time Frame: 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.
Baseline to Week 12
Change From Baseline in the Overall Dermatology Life Quality Index (DLQI) Score at Week 12
Time Frame: 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.
Baseline to Week 12
Percentage of Angioedema-free Days From Week 4 to Week 12
Time Frame: 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.
Week 4 to Week 12
Time to Minimally Important Difference (MID) Response in the Weekly Itch Severity Score by Week 12
Time Frame: 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.
Baseline to Week 12
Percentage of Weekly Itch Severity Score MID Responders at Week 12
Time Frame: Baseline to Week 12
The percentage of participants with an itch severity score at 12 Weeks at least 5 points lower than at Baseline.
Baseline to Week 12
Percentage of Complete Responders (UAS7 = 0) at Week 12
Time Frame: Week 12
A complete responder was defined as a participant with a UAS7 score = 0 at Week 12.
Week 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Genentech, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2011

Primary Completion (Actual)

October 1, 2012

Study Completion (Actual)

October 1, 2012

Study Registration Dates

First Submitted

January 27, 2011

First Submitted That Met QC Criteria

January 28, 2011

First Posted (Estimate)

February 1, 2011

Study Record Updates

Last Update Posted (Estimate)

November 27, 2013

Last Update Submitted That Met QC Criteria

November 4, 2013

Last Verified

November 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Q4881g
  • GA00887

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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