Efficacy and Safety of Omalizumab in Adults (18-70 Years) With Moderate to Severe Chronic Urticaria

A Randomized, 24 Weeks, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Assess the Efficacy and Safety of Omalizumab in Adult Patients With Chronic Urticaria Who Exhibit IgE Against Thyroperoxidase

This study evaluated the safety and efficacy of omalizumab in adult patients with moderate to severe chronic urticaria who exhibit IgE against thyroperoxidase.

Study Overview

• Status: Completed
• Conditions: Chronic Urticaria
• Intervention / Treatment: Drug: Omalizumab 75-375 mg; Drug: Loratadine; Drug: Placebo to omalizumab; Drug: Clemastine

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany
    • Novartis Investigative Site
  • Bonn, Germany
    • Novartis Investigative Site
  • Dresden, Germany
    • Novartis Investigative Site
  • Giessen, Germany
    • Novartis Investigative Site
  • Hamburg, Germany
    • Novartis Investigative Site
  • Hannover, Germany
    • Novartis Investigative Site
  • Koeln, Germany
    • Novartis Investigative Site
  • Leipzig, Germany
    • Novartis Investigative Site
  • Luebeck, Germany
    • Novartis Investigative Site
  • Mainz, Germany
    • Novartis Investigative Site
  • Munich, Germany
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Males or females from 18-70 years of age
• Body weight ≥ 20 kg and ≤ 150 kg and with a total serum IgE level ≥ 30 IU/mL and ≤ 700 IU/mL
• Specific serum IgE anti-TPO level ≥ 8.0 IU/mL, documented within 3 months prior to randomization or time of pre-screening
• Diagnosis of moderate to severe chronic urticaria
• Subject's current episode of chronic urticaria according to the European Academy of Allergology and Clinical Immunology/Global Allergy and Asthma European Network/European Dermatology Forum (EAACI/GA2LEN/EDF) guideline at the time of screening
• Current episode of chronic urticaria has not responded to the approved marketed dose of antihistamine for 2 weeks or longer
• Urticaria activity score (UAS) ≥ 0 at any of the 7 days of the first section of the screening period
• UAS7 ≥ 10 at the time of randomization

Exclusion criteria:

• Females of child-bearing potential or breast feeding
• Present or past medical conditions that could have interfered with the study results
• Randomized into any other omalizumab study or who had received omalizumab
• Received investigational drugs within 30 days of enrollment

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Omalizumab 75-375 mg; Omalizumab was dosed at 75 to 375 mg according to baseline IgE and body weight as described in dosing tables in the study protocol. Dosing occurred subcutaneously every 2 or 4 weeks depending on dose.	Drug: Omalizumab 75-375 mg; Omalizumab was supplied as lyophilized, sterile powder in a single-use, 5 ml vial designed to deliver 150 mg of omalizumab upon reconstitution with 1.4 ml sterile water for injection.; Other Names: Xolair; Drug: Loratadine; All participants received antihistamines on demand (loratadine and clemastine), as the trial was designed to investigate the effect of omalizumab as an add-on to antihistamines in people with chronic urticaria (CU). Administration of antihistamines is the current gold standard treatment of CU. A significant proportion of people with CU is not well controlled by this standard or by using high doses of antihistamines.; Other Names: Lorano®
Placebo Comparator: Placebo to omalizumab; Placebo to omalizumab was dosed at 75 to 375 mg according to baseline IgE and body weight as described in dosing tables in the study protocol. Dosing occurred subcutaneously every 2 or 4 weeks depending on dose.	Drug: Loratadine; All participants received antihistamines on demand (loratadine and clemastine), as the trial was designed to investigate the effect of omalizumab as an add-on to antihistamines in people with chronic urticaria (CU). Administration of antihistamines is the current gold standard treatment of CU. A significant proportion of people with CU is not well controlled by this standard or by using high doses of antihistamines.; Other Names: Lorano®; Drug: Placebo to omalizumab; Placebo to omalizumab was supplied as lyophilized, sterile powder in a single-use, 5 ml vial designed to deliver 150 mg placebo to omalizumab upon reconstitution with 1.4 ml sterile water for injection.; Drug: Clemastine; All participants received antihistamines on demand (loratadine and clemastine), as the trial was designed to investigate the effect of omalizumab as an add-on to antihistamines in people with chronic urticaria (CU). Administration of antihistamines is the current gold standard treatment of CU. A significant proportion of people with CU is not well controlled by this standard or by using high doses of antihistamines.; Other Names: Tavegil®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the Weekly Urticaria Activity Score (UAS7) From Baseline to the End of the Study (Week 24)	The UAS is a composite diary-recorded score with numeric severity ratings (0=none to 3=intense) for the number of wheals per 24 hours and the intensity of the pruritus. The total daily score (sum of the wheal and pruritus scores) ranges from 0 to 6. Because of variations in chronic urticaria disease intensity, assessment of disease activity was based on a weekly (7 days) UAS score called UAS7, that is, the sum of the daily UASs, ranging from 0 to 42 per week. A higher score indicates worse disease. A negative change score (Week 24 score minus Baseline score) indicates improvement.	Baseline to end of the study (Week 24)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients With Wheals, Erythemas, Pruritus, and Angioedemas at the End of the Study	Patients kept a daily diary of the number of wheals and erythema and the severity of pruritus and angioedemas during the study.	At the end of the study (Week 24)
Standardized (With Respect to Length of Time) Area Under the Curve (AUC) for the Urticaria Activity Score (UAS) From Baseline to the End of the Study (Week 24)	The UAS is a composite diary-recorded score with numeric severity ratings (0=none to 3=intense) for the number of wheals per 24 hours and the intensity of the pruritus. The total daily score (sum of the wheal and pruritus scores) ranges from 0 to 6. A higher score indicates worse disease. AUC was calculated from daily UASs where no urticaria medication was taken using the trapezoidal rule. The standardized AUC UAS was calculated as the sum of trapezoids divided by the length of time.	Baseline to the end of the study (Week 24)
Use of Concomitant and Rescue Medications	Data was collected from the patients' diaries about the number of clemastine and loratadine pills taken during the last 7 days of each month of the study.	At Weeks 4, 8, 12, 16, 20, and 24
Change in the Dermatology Life Quality Index (DLQI) Score From Baseline to the End of the Study (Week 24)	The DLQI is a dermatology-specific quality of life (QoL) questionnaire designed for use in patients over 16 years of age. Patients are asked to respond to each of 10 questions on a 4-point Likert scale in regard to how much their skin problem has affected their life over the last week (0=not at all, 1=a little, 2=a lot, 3=very much). The overall (total) DLQI score (range=0 to 30) is calculated by summing the scores of all 10 questions. The higher the score, the more QoL is impaired. A negative change score (Week 24 score minus Baseline score) indicates improvement.	Baseline to the end of the study (Week 24)
Change in the Skindex Score From Baseline to the End of the Study (Week 24)	Skindex is a 30-item questionnaire with 3 scores (functioning, emotions,symptoms) and a composite score (average scale score) that assesses the effects of skin disease on patients' quality of life (QoL). Item responses are standardized on a scale from 0 to 100. The mean of all 61 items was calculated. A higher score indicates a lower QoL. A negative change score (Week 24 score minus Baseline score) indicates improvement.	Baseline to the end of the study (Week 24)
Change in Chronic Urticaria Quality of Life (CU-Q2oL) Scores From Baseline to the End of the Study (Week 24)	The CU-Q2oL (German version) is a questionnaire that measures the relative burden of chronic urticaria on subjective well-being. It has 23 questions in 3 domains (symptoms, general impairment, difficulties and problems due to urticaria). Patients are asked to respond how much they are troubled by each problem on a 5-point Likert scale (1=not at all to 5=very much). Each domain and the overall (total) scores are normalized to a scale of 1 to 100. A higher score indicates lower QoL. A negative change score (Week 24 score minus Baseline score) indicates improvement.	Baseline to the end of the study (Week 24)
Patient's Global Assessment of Their Chronic Urticaria Symptoms	Patients made a global assessment of their chronic urticaria symptoms on a 4-point Likert scale (none, mild moderate, severe) at Baseline and again at the end of the study. The number of patients in each category is reported.	At Baseline and at the end of the study (Week 24)
Investigator's Global Assessment of the Patient's Chronic Urticaria Symptoms	The investigator made a global assessment of the patient's chronic urticaria symptoms on a 4-point Likert scale (none, mild, moderate, severe) at Baseline and again at the end of the study. The number of patients in each category is reported.	At Baseline and at the end of the study (Week 24)

Collaborators and Investigators

• Sponsor: Novartis

Study record dates

Study Major Dates

• Study Start: May 1, 2007
• Primary Completion (Actual): April 1, 2009
• Study Completion (Actual): April 1, 2009

Study Registration Dates

• First Submitted: June 1, 2007
• First Submitted That Met QC Criteria: June 1, 2007
• First Posted (Estimate): June 4, 2007

Study Record Updates

• Last Update Posted (Estimate): October 21, 2011
• Last Update Submitted That Met QC Criteria: September 14, 2011
• Last Verified: September 1, 2011

More Information

Terms related to this study

• Keywords: Chronic urticaria, omalizumab, thyroperoxidase, IgE
• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Skin Diseases, Vascular; Hypersensitivity; Urticaria; Chronic Urticaria; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Immunologic Factors; Dermatologic Agents; Anti-Asthmatic Agents; Respiratory System Agents; Anti-Allergic Agents; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Antipruritics; Histamine H1 Antagonists, Non-Sedating; Antibodies, Monoclonal; Omalizumab; Loratadine; Clemastine
• Other Study ID Numbers: CIGE025ADE05