A Study to Evaluate the Efficacy, Response Duration and Safety of Xolair (Omalizumab) in Patients With Chronic Idiopathic Urticaria (CIU)/Chronic Spontaneous Urticaria (CSU) Who Remain Symptomatic Despite Antihistamine Treatment (H1)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Genentech
ClinicalTrials.gov Identifier:
NCT01292473
First received: February 7, 2011
Last updated: October 9, 2013
Last verified: October 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-dosed H1 antihistamine treatment.


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

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Genentech:

Primary Outcome Measures:
  • Change From Baseline in the Weekly Itch Severity Score at Week 12 [ Time Frame: Baseline, 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 in the Weekly Urticaria Activity Score (UAS7) at Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    The urticaria activity score (UAS) is a composite of scores on a scale of 0 (none) to 3 (intense/severe) for 1) the number of wheals (hives); and 2) the intensity of the itch, measured twice daily (morning and evening). Daily UAS is the average of morning and evening scores (ranging from 0-6) and the UAS7 is the sum of the daily UAS over 7 days (ranging from 0-42). Baseline UAS7 is calculated using data from the 7 days prior to the first treatment date. A higher UAS indicates more urticaria activity. A negative change score indicates improvement.

  • Change From Baseline in the Weekly Number of Hives Score at Week 12 [ Time Frame: Baseline, 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: by 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.

    The MID response for weekly itch severity score was defined as a reduction from baseline in weekly itch severity score of 5 points or more. The time to weekly itch severity score MID response was defined as the time (in weeks) from Day 1 to the study week when weekly itch severity score MID response was first achieved.


  • Percentage of Participants With a UAS7 Less Than or Equal to 6 at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    The urticaria activity score (UAS) is a composite of scores on a scale of 0 (none) to 3 (intense/severe) for 1) the number of wheals (hives); and 2) the intensity of the itch, measured twice daily (morning and evening). Daily UAS is the average of morning and evening scores (ranging from 0-6) and the UAS7 is the sum of the daily UAS over 7 days (ranging from 0-42). Baseline UAS7 is calculated using data from the 7 days prior to the first treatment date. A higher UAS indicates more urticaria activity. A negative change score indicates improvement.

  • Percentage of Weekly Itch Severity Score MID Responders at Week 12 [ Time Frame: Baseline, 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.

    The MID response for weekly itch severity score was defined as a reduction from baseline in weekly itch severity score of 5 points or more. This outcome measure shows the percentage of participants classified as MID Responders at Week 12, meaning their weekly itch severity scores at Week 12 were at least 5 points lower than at Baseline.


  • Change From Baseline in the Weekly Size of the Largest Hive Score at Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    The size of the largest hive is assessed twice daily (morning and evening) on a scale of 0 (none) to 3 (> 2.5 cm). The daily score is the average of the morning and evening scores. The weekly size of the largest hive score is the sum of the daily scores over 7 days, and ranges from 0 to 21. The Baseline weekly size of the largest hive score is the sum of daily scores 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) at Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    The dermatology life quality index (DLQI) is a 10-item dermatology-specific health-related quality of life measure. Participants rate 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 a patient reported as angioedema-free 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.


Enrollment: 323
Study Start Date: March 2011
Study Completion Date: June 2012
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Placebo
Placebo subcutaneously (sc) every 4 weeks
Drug: Placebo
Placebo was supplied lyophilized in vials.
Drug: Omalizumab
Omalizumab was supplied lyophilized in vials.
Other Name: Xolair
Experimental: Omalizumab 75 mg
Omalizumab 75 mg sc every 4 weeks
Drug: Omalizumab
Omalizumab was supplied lyophilized in vials.
Other Name: Xolair
Experimental: Omalizumab 150 mg
Omalizumab 150 mg sc every 4 weeks
Drug: Omalizumab
Omalizumab was supplied lyophilized in vials.
Other Name: Xolair
Experimental: Omalizumab 300 mg
Omalizumab 300 mg sc every 4 weeks.
Drug: Omalizumab
Omalizumab was supplied lyophilized in vials.
Other Name: Xolair

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
  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) 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.
  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: NCT01292473

  Hide Study Locations
Locations
United States, California
La Jolla, California, United States, 92037
Los Angeles, California, United States, 90045
Redwood City, California, United States, 94063
Walnut Creek, California, United States, 94598
United States, Colorado
Denver, Colorado, United States, 80206
United States, Florida
Miami, Florida, United States, 33173
United States, Georgia
Savannah, Georgia, United States, 31405
Woodstock, Georgia, United States, 30188
United States, Illinois
Shiloh, Illinois, United States, 62269
United States, Indiana
Indianapolis, Indiana, United States, 46256
United States, Kansas
Overland Park, Kansas, United States, 66210
United States, Maryland
Baltimore, Maryland, United States, 21237
Wheaton, Maryland, United States, 20902
United States, Michigan
Ypsilanti, Michigan, United States, 48197
United States, Nebraska
Omaha, Nebraska, United States, 68130
Omaha, Nebraska, United States, 68131
United States, New Jersey
Brick, New Jersey, United States, 08724
United States, New York
Bayside, New York, United States, 11361
Bronx, New York, United States, 10461
Brooklyn, New York, United States, 11203
North Syracuse, New York, United States, 13212
Rochester, New York, United States, 14642
Rockville Centre, New York, United States, 11570
United States, North Carolina
Asheville, North Carolina, United States, 28801
United States, Ohio
Canton, Ohio, United States, 44718
Cincinnati, Ohio, United States, 45231
United States, Pennsylvania
Philadelphia, Pennsylvania, United States, 19140
Pittsburgh, Pennsylvania, United States, 15213
Pittsburgh, Pennsylvania, United States, 15241
United States, Rhode Island
Providence, Rhode Island, United States, 02906
United States, Texas
El Paso, Texas, United States, 79903
United States, Utah
Sandy, Utah, United States, 84070
United States, Washington
Seattle, Washington, United States, 98105
Spokane, Washington, United States, 99204
United States, Wisconsin
Madison, Wisconsin, United States, 53715
Milwaukee, Wisconsin, United States, 53226
Denmark
Arhus, Denmark, 8000
Copenhagen, Denmark, 2900
France
Montpellier, France, 34295
Nice Cedex 3, France, 06200
Paris, France, 75475
Germany
Bonn, Germany, 53127
Hannover, Germany, 30449
Leipzig, Germany, D-'04103
Mainz, Germany, 55131
Muenster, Germany, 48149
München, Germany, 80802
Italy
Genova, Italy, 16132
Milano, Italy, 20122
Milano, Italy, 20132
Poland
Gdansk, Poland, 80-211
Krakow, Poland, 31-913
Lodz, Poland, 90-265
Warszawa, Poland, 02-256
Wroclaw, Poland, 54-239
Spain
Barcelona, Spain, 08003
Madrid, Spain, 28041
Turkey
Ankara, Turkey, 06100
Istanbul, Turkey, 34372
Izmir, Turkey, 35100
Kayseri, Turkey, 38039
Sponsors and Collaborators
Genentech
Investigators
Study Director: Karin E Rosén, MD, PhD Genentech
  More Information

No publications provided by Genentech

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Genentech
ClinicalTrials.gov Identifier: NCT01292473     History of Changes
Other Study ID Numbers: Q4882g
Study First Received: February 7, 2011
Results First Received: June 17, 2013
Last Updated: October 9, 2013
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on August 26, 2014