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

Purpose

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

Condition	Intervention	Phase
Chronic Urticaria	Drug: Omalizumab 75-375 mg Drug: Placebo to omalizumab Drug: Loratadine Drug: Clemastine	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	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

Resource links provided by NLM:

MedlinePlus related topics: Hives

Drug Information available for: Omalizumab

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

Change in the Weekly Urticaria Activity Score (UAS7) From Baseline to the End of the Study (Week 24) [ Time Frame: Baseline to 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.

Secondary Outcome Measures:

Number of Patients With Wheals, Erythemas, Pruritus, and Angioedemas at the End of the Study [ Time Frame: At the end of the study (Week 24) ]
Patients kept a daily diary of the number of wheals and erythema and the severity of pruritus and angioedemas during the study.
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) [ Time Frame: 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.
Use of Concomitant and Rescue Medications [ Time Frame: At Weeks 4, 8, 12, 16, 20, and 24 ]
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.
Change in the Dermatology Life Quality Index (DLQI) Score From Baseline to the End of the Study (Week 24) [ Time Frame: 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.
Change in the Skindex Score From Baseline to the End of the Study (Week 24) [ Time Frame: 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.
Change in Chronic Urticaria Quality of Life (CU-Q2oL) Scores From Baseline to the End of the Study (Week 24) [ Time Frame: 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.
Patient's Global Assessment of Their Chronic Urticaria Symptoms [ Time Frame: At Baseline and at the end of the study (Week 24) ]
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.
Investigator's Global Assessment of the Patient's Chronic Urticaria Symptoms [ Time Frame: At Baseline and at the end of the study (Week 24) ]
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.


Enrollment:	49
Study Start Date:	May 2007
Study Completion Date:	April 2009
Primary Completion Date:	April 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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 Name: 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 Name: 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: 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: 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 Name: Lorano® 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 Name: Tavegil®

Arms

Assigned Interventions

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 Name: 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 Name: 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: 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: 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 Name: Lorano®

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 Name: Tavegil®

Eligibility


Ages Eligible for Study:	18 Years to 70 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

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: NCT00481676

Locations


Germany
Novartis Investigative Site
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

Sponsors and Collaborators

Novartis

Investigators


Study Director:	Novartis Pharmaceuticals	Novartis Pharmaceuticals

More Information


Responsible Party:	Novartis
ClinicalTrials.gov Identifier:	NCT00481676 History of Changes
Other Study ID Numbers:	CIGE025ADE05
Study First Received:	June 1, 2007
Results First Received:	December 17, 2010
Last Updated:	September 14, 2011

Keywords provided by Novartis:


Chronic urticaria, omalizumab, thyroperoxidase, IgE

Additional relevant MeSH terms:


Urticaria Skin Diseases, Vascular Skin Diseases Hypersensitivity, Immediate Hypersensitivity Immune System Diseases Clemastine Loratadine Omalizumab Antibodies, Monoclonal Antipruritics Dermatologic Agents	Histamine H1 Antagonists Histamine Antagonists Histamine Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Physiological Effects of Drugs Anti-Allergic Agents Anti-Asthmatic Agents Respiratory System Agents Immunologic Factors Histamine H1 Antagonists, Non-Sedating

ClinicalTrials.gov processed this record on June 23, 2017