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

• ClinicalTrials.gov Identifier: NCT00481676
• Recruitment Status: Completed
• First Posted: June 4, 2007
• Results First Posted: October 21, 2011
• Last Update Posted: October 21, 2011
• Sponsor: Novartis
• Information provided by (Responsible Party): Novartis

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Chronic Urticaria	Drug: Omalizumab 75-375 mg; Drug: Placebo to omalizumab; Drug: Loratadine; Drug: Clemastine	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 49 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (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
• Study Start Date: May 2007
• Actual Primary Completion Date: April 2009
• Actual Study Completion Date: April 2009

Arms and Interventions

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 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®

Outcome Measures

Primary Outcome Measures :

1. 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 :

1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• 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

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
• Other Study ID Numbers: CIGE025ADE05
• First Posted: June 4, 2007
• Results First Posted: October 21, 2011
• Last Update Posted: October 21, 2011
• Last Verified: September 2011

Keywords provided by Novartis:

Chronic urticaria, omalizumab, thyroperoxidase, IgE

Additional relevant MeSH terms:

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