Effect of Omalizumab on Expression of IgE Receptors in Adults With Severe, Inadequately Controlled Allergic Asthma

NCT00454051 | Completed Phase 4 Results DMC

• 1 other identifier: CIGE025AFR02
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to evaluate the expression of IgE high affinity receptors (the part of the cell associated with allergic response) in patients suffering from uncontrolled severe asthma despite long term treatment with high dose of inhaled corticosteroid and long acting Beta-2 agonist.

Conditions

Asthma

Keywords

Asthma, anti-immunoglobulin E, omalizumab, IgE receptors

Outcome Measures

Primary Outcomes (2)

• Change (%) From Baseline in FcεRI (High-affinity IgE Receptor) Expression on Blood Basophils and Dendritic Cells After 16 Weeks of Treatment With Omalizumab as Compared With Placebo

  Blood was drawn from participants at baseline and at Week 16. Basophils and dendritic cells expressing FcεRI were counted and the percentage was calculated. Fluorescence was used to label FcεRI so that they could be visualized. The greater the fluorescence intensity the greater FcεRI expression. The change from baseline is described by the difference (%) between the baseline value, before the first study drug administration, and the value observed at the end of study, expressed as a percent of the baseline value.

  Baseline and Week 16

• Change (%) From Baseline in Mean Fluorescence Intensity of FcεRI After 16 Weeks of Treatment With Omalizumab as Compared With Placebo

  Blood was drawn from participants at baseline and at week 16. Basophils and dendritic cells expressing FcεRI were counted and the percentage was calculated. Fluorescence was used to label FcεRI so that they could be visualized. The greater the fluorescence intensity the greater FcεRI expression. The change from baseline is described by the difference (%) between the baseline value, before the first study drug administration, and the value observed at the end of study, expressed as a percent of the baseline value.

  Baseline and Week 16

Secondary Outcomes (11)

• Change (%) From Baseline in Percent of Basophils and Dendritic Cells Expressing FcεRI After 4, 8, 12 and 16 Weeks of Treatment

  Baseline, Weeks 4, 8, 12 and 16

• Change (%) From Baseline in the Mean Fluorescence Intensity of FcεRI After 4, 8, 12 and 16 Weeks of Treatment

  Baseline, Weeks 4, 8, 12, and 16

• Change From Baseline in the Number of Days With Asthma Symptoms Per Week

  Baseline (the 4 week screening period prior to randomization) and End of Study (Weeks 12 - 16)

• Change From Baseline in the Number of Puffs of Rescue Medication Per Week

  Baseline (the 4 week screening period prior to randomization) and End of Study (Weeks 12 - 16)

• Change From Baseline in the Number of Nights With Awakenings Per Week

  Baseline (the 4 week screening period prior to randomization) and End of Study (Weeks 12 - 16)

Study Arms (2)

Omalizumab

ACTIVE COMPARATOR

Omalizumab was injected subcutaneously every 2 weeks or every 4 weeks for 16 weeks. Dose and dosing interval were determined based on patient body weight and pre-treatment serum IgE level.

Drug: Omalizumab

Placebo

PLACEBO COMPARATOR

Placebo was injected subcutaneously every 2 weeks or every 4 weeks for 16 weeks.

Drug: placebo

Interventions

Omalizumab DRUG

Omalizumab was supplied as a sterile, freeze dried preparation, to be reconstituted to deliver 150mg of omalizumab. Each vial was reconstituted with 1.4ml of sterile water for injection. The appropriate dose and dosing frequency of omalizumab were determined by baseline total IgE and body weight. A dosing table was used following the European Summary of Product Characteristics (SmPC) of omalizumab.

Omalizumab

placebo DRUG

Placebo was a physiological salt solution, administered according to the same administration scheme to respect the same dosing frequency and injected volume.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults aged \>= 18 years.
• Patients with severe persistent allergic asthma with the following characteristics:
• FEV1 (Forced Expiratory Volume in One Second) \<80% of predicted.
• Frequent daily symptoms (\>=4 days/week on average) or nocturnal awakening (\>=1/week on average).
• Multiple severe asthma exacerbations: either \>=2 severe asthma exacerbations having required an unscheduled medical intervention with systemic corticosteroid in the past year, or hospitalization (including emergency room treatment) for an asthma exacerbation in the past year.
• Despite a high dose inhaled corticosteroid \>1000 mg beclomethasone dipropionate or equivalent and a inhaled long-acting B2-agonist.
• With an allergy to a perennial allergen demonstrated with convincing criteria, i.e. positive prick skin test or in vitro reactivity to a perennial aeroallergen (RAST).
• Total serum IgE level \>= 30 to \<=700 IU/ml and suitable serum total IgE level and weight according to Xolair dosing tablets.

You may not qualify if:

• Age \< 18 years.
• Smoking history \> 20 pack years.
• Patients who have had an asthma exacerbation during the 4 weeks prior to randomization
• History of food or drug related severe anaphylactoid or anaphylactic reaction
• Elevated serum IgE levels for reasons other than allergy (e.g. parasite infections, hyperimmunoglobulin E syndrome, Wiskott-Aldrich Syndrome or allergic bronchopulmonary aspergillosis).
• Patients with active cancer, suspicion of cancer or any history of cancer.
• Pregnant women.
• Known hypersensitivity to omalizumab or to one of its components.
• Patients already treated with omalizumab (indeed a previous treatment with omalizumab could have modified the FceRI expression).
• Patients who had participated in a clinical trial in the past 3 months.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (1)

Novartis Investigator site

Rueil-Malmaison, France

Location

Related Publications (1)

• Chanez P, Contin-Bordes C, Garcia G, Verkindre C, Didier A, De Blay F, de Lara MT, Blanco P, Moreau JF, Robinson P, Bourdeix I, Trunet P, Le Gros V, Humbert M, Molimard M. Omalizumab-induced decrease of FcxiRI expression in patients with severe allergic asthma. Respir Med. 2010 Nov;104(11):1608-17. doi: 10.1016/j.rmed.2010.07.011. Epub 2010 Aug 30.

  PMID: 20801010 DERIVED

MeSH Terms

Conditions

Asthma

Interventions

Omalizumab

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Anti-Idiotypic; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Serum Globulins; Globulins

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: March 28, 2007
• First Posted: March 29, 2007
• Study Start: December 1, 2006
• Primary Completion: March 1, 2008
• Study Completion: March 1, 2008
• Last Updated: August 8, 2011
• Results First Posted: August 1, 2011

Record last verified: 2011-08

Locations

FR (1)