Efficacy and Safety of Omalizumab in Children (6 - < 12 Years) With Moderate-severe, Inadequately Controlled Allergic Asthma - Full Text View

Sponsor:	Novartis Pharmaceuticals
Information provided by:	Novartis
ClinicalTrials.gov Identifier:	NCT00079937

Purpose

A substance called immunoglobulin E (IgE), which is naturally produced by our body, has a key role in generating asthma attacks. In patients with allergies, there is an exaggerated production of IgE in response to specific substances such as pollens. Omalizumab is a new drug that inactivates IgE. This study tested the safety and efficacy of omalizumab against asthma attacks in children with allergic asthma.

Condition	Intervention	Phase
Asthma	Drug: Omalizumab Drug: Placebo Drug: Fluticasone	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A 1 Year, Randomized, Double-blind, Parallel-group, Placebo-controlled, Multicenter Evaluation of Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Omalizumab in Children (6 - < 12 Years) With Moderate-severe, Persistent, Inadequately Controlled Allergic Asthma

Resource links provided by NLM:

MedlinePlus related topics: Allergy Asthma

Drug Information available for: Fluticasone propionate Fluticasone Omalizumab

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

Rate of Clinically Significant Asthma Exacerbations Per Patient in the 24-week Fixed-dose Steroid Treatment Period [ Time Frame: Baseline to end of the fixed-dose steroid treatment period (Week 24) ] [ Designated as safety issue: No ]
A clinically significant asthma exacerbation was defined as a worsening of asthma symptoms, as judged clinically by the investigator, requiring doubling of the baseline inhaled corticosteroid dose and/or treatment with systemic rescue corticosteroids for at least 3 days. The exacerbations rate per patient was derived using Poisson model adjusted by time at risk and the following covariates: country, exacerbation history, and dose schedule. A patient's person-days at risk was taken as the total amount of time (in days) he/she spent in the 24-week fixed-dose steroid treatment period.
Percentage of Participants With at Least 1 Adverse Event [ Time Frame: Baseline to end of the study (Week 68) ] [ Designated as safety issue: Yes ]
See Adverse Events module for details.

Secondary Outcome Measures:

Change in Mean Nocturnal Asthma Symptom Score From Baseline to the End (Last 4 Weeks) of the 24-week Fixed-dose Steroid Treatment Period [ Time Frame: Baseline to the end (last 4 weeks) of the 24-week fixed-dose steroid treatment period ] [ Designated as safety issue: No ]
Nocturnal asthma symptom was measured daily on a scale of 0 to 4 in response to the question "How did you sleep last night?", with 0 as the best response and 4 as the worst response. The mean of the last 4 weeks of the 24-week fixed-dose steroid treatment period was calculated; for patients who discontinued prematurely, the mean of the last 28 days before discontinuation was calculated. A positive change score indicated improvement.
Rate of Clinically Significant Asthma Exacerbations Per Patient in the 52-week Treatment Period [ Time Frame: Baseline to end of the treatment period (Week 52) ] [ Designated as safety issue: No ]
A clinically significant asthma exacerbation was defined as a worsening of asthma symptoms, as judged clinically by the investigator, requiring doubling of the baseline inhaled corticosteroid dose and/or treatment with systemic rescue corticosteroids for at least 3 days. The exacerbations rate per patient was derived using Poisson model adjusted by time at risk and the following covariates: country, exacerbation history, and dose schedule. A patient's person-days at risk was taken as the total amount of time (in days) he/she spent in the 52-week treatment period.
Change in Mean Daily Number of Puffs of Asthma Rescue Medication From Baseline to the End (Last 4 Weeks) of the 24-week Fixed-dose Steroid Treatment Period [ Time Frame: Baseline to the end (last 4 weeks) of the 24-week fixed-dose steroid treatment period ] [ Designated as safety issue: No ]
Patients were instructed to record the number of puffs of rescue medication they took twice daily in a diary. The mean daily number of puffs during the last 4 weeks of the 24-week fixed-dose steroid treatment period was calculated; for patients who discontinued prematurely, the mean of the last 28 days before discontinuation was calculated. A positive change score indicated reduced use of rescue medication.
Change in Pediatric Asthma Quality of Life Questionnaire (Standardized) [PAQLQ(S)] Scores From Baseline to the End of the 24-week Fixed-dose Steroid Treatment Period (Week 24) [ Time Frame: Baseline to the end of the 24-week fixed-dose steroid treatment period (Week 24) ] [ Designated as safety issue: No ]
The PAQLQ measures functional problems that are most troublesome to children with asthma. The PAQLQ has 23 questions in 3 domains (activity limitation=5, emotional function=8, and symptoms=10). Children are asked to respond to each of the 23 questions on a 7-point Likert scale (1=maximum impairment to 7=no impairment). The overall (total) PAQLQ score is the mean of all 23 questions; the individual domain scores are the means of the questions in each domain. The analysis included country, baseline PAQLQ value, and dosing schedule (2-weekly or 4-weekly) as factors and covariates.

Enrollment:	628
Study Start Date:	April 2004
Study Completion Date:	March 2008
Primary Completion Date:	March 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Omalizumab Participants received omalizumab administered by subcutaneous injection every 2 or 4 weeks for a duration of 52 weeks. The omalizumab dose was based on the patient's body weight and total serum IgE level at Screening. The first 24 weeks of the treatment period was a fixed steroid phase where the steroid dose was maintained constant; in the following 28 weeks the steroid dose was adjustable, depending on the patient's condition. Following the 52-week treatment period, patients were followed up for an additional 16 weeks.	Drug: Omalizumab The omalizumab dose administered, based on the patient's body weight and total serum IgE level at Screening, and the number of injections and injection volume was determined from the dosing tables in the protocol. Omalizumab 75 to 375 mg was administered subcutaneous (SC) every 2 or 4 weeks depending on the dose. Drug: Fluticasone Patients entered the study using their current formulation of any inhaled steroid (proprietary drug and device) ≥ 200 μg/day equivalent of fluticasone administered with a dry-powder inhaler.
Placebo Comparator: Placebo Placebo was administered by subcutaneous injection every 2 or 4 weeks depending on the dosing schedule in the protocol for a total of 52 weeks. The first 24 weeks of the treatment period was a fixed steroid phase where the steroid dose was maintained constant; in the following 28 weeks the steroid dose was adjustable, depending on the patient's condition. Following the 52-week treatment period, patients were followed up for an additional 16 weeks.	Drug: Placebo Placebo was administered subcutaneous (SC) every 2 or 4 weeks depending on the dosing schedule in the protocol. Drug: Fluticasone Patients entered the study using their current formulation of any inhaled steroid (proprietary drug and device) ≥ 200 μg/day equivalent of fluticasone administered with a dry-powder inhaler.

Arms

Assigned Interventions

Experimental: Omalizumab

Participants received omalizumab administered by subcutaneous injection every 2 or 4 weeks for a duration of 52 weeks. The omalizumab dose was based on the patient's body weight and total serum IgE level at Screening. The first 24 weeks of the treatment period was a fixed steroid phase where the steroid dose was maintained constant; in the following 28 weeks the steroid dose was adjustable, depending on the patient's condition. Following the 52-week treatment period, patients were followed up for an additional 16 weeks.

Drug: Omalizumab

The omalizumab dose administered, based on the patient's body weight and total serum IgE level at Screening, and the number of injections and injection volume was determined from the dosing tables in the protocol. Omalizumab 75 to 375 mg was administered subcutaneous (SC) every 2 or 4 weeks depending on the dose.

Drug: Fluticasone

Patients entered the study using their current formulation of any inhaled steroid (proprietary drug and device) ≥ 200 μg/day equivalent of fluticasone administered with a dry-powder inhaler.

Placebo Comparator: Placebo

Placebo was administered by subcutaneous injection every 2 or 4 weeks depending on the dosing schedule in the protocol for a total of 52 weeks. The first 24 weeks of the treatment period was a fixed steroid phase where the steroid dose was maintained constant; in the following 28 weeks the steroid dose was adjustable, depending on the patient's condition. Following the 52-week treatment period, patients were followed up for an additional 16 weeks.

Drug: Placebo

Placebo was administered subcutaneous (SC) every 2 or 4 weeks depending on the dosing schedule in the protocol.

Drug: Fluticasone

Patients entered the study using their current formulation of any inhaled steroid (proprietary drug and device) ≥ 200 μg/day equivalent of fluticasone administered with a dry-powder inhaler.

Detailed Description:

This study was designed to provide one year efficacy and safety data for subcutaneous (SC) omalizumab, compared to placebo in children (6 to < 12 years) with moderate to severe persistent asthma who have inadequate asthma control despite treatment according to National Heart, Lung and Blood Institute (NHLBI) step 3 or 4 (at least medium dose inhaled corticosteroids with or without other controller asthma medications).

Eligibility

Ages Eligible for Study:	6 Years to 11 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion criteria:

Parent or legal guardian was informed of the study procedures and medications and gave written informed consent.
Outpatient males and females aged 6 - < 12 years on study entry, with body weight between 20 and 150 kg.
Total serum IgE level ≥ 30 to ≤ 1300 IU.
Diagnosis of allergic asthma ≥ 1 year duration, according to American Thoracic Society (ATS) criteria, and a screening history consistent with clinical features of moderate or severe persistent asthma according to National Heart Lung and Blood Institute (NHLBI) guidelines.
Positive prick skin test to at least one perennial allergen, documented within the past 2 years or taken at Screening. A radioallergosorbent test (RAST) could have been performed for patients with a borderline skin prick test result after consultation with Novartis clinical personnel.
Patients with ≥ 12% increase in forced expiratory volume in 1 second (FEV1) over starting value within 30 minutes of taking up to 4 puffs (4x100 µg) salbutamol (albuterol) or nebulized salbutamol up to 5 mg (or equivalent of alternative B2-agonist) documented within the past year, at screening, during the run-in period, or prior to randomization. Patients were not to take their long acting B2-agonist (LABA) medication within 12 hours of reversibility testing.
Clinical features of moderate or severe persistent asthma (at least step 3) despite therapy at step 3 or 4 (at least medium dose inhaled corticosteroid (ICS) - fluticasone dry-powder inhaler (DPI) ≥ 200 mg/day or equivalent with or without other controller medications).
Documented history of experiencing asthma exacerbations and demonstrated inadequate symptom control during the last 4 weeks of run-in despite receiving an equivalent dose of fluticasone DPI ≥ 200 mg/day total daily ex-valve dose.

Exclusion criteria:

Patients who received systemic corticosteroids for reasons other than asthma, beta-adrenergic antagonists by any route, anticholinergics within 24 hours of Screening, methotrexate, gold salts, cyclosporin or troleandomycin, or had received desensitization therapy with less than 3 months of stable maintenance doses prior to Screening.
Patients with a history of food or drug related severe anaphylactoid or anaphylactic reaction, a history of allergy to antibiotics, with aspirin or other non-steroidal anti-inflammatory drugs (NSAID)-related asthma (unless the NSAID could be avoided), with active lung disease or acute sinusitis/chest infection, elevated serum IgE levels for other reasons, presence/history of a clinically significant uncontrolled systemic disease, cancer, abnormal, electrocardiogram (ECG) in the previous month, or platelets ≤ 100 x 109/L or clinically significant laboratory abnormalities at Screening.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00079937

Show 56 Study Locations

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

Study Director:

Novartis Pharmaceuticals

More Information

No publications provided by Novartis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Lanier B, Bridges T, Kulus M, Taylor AF, Berhane I, Vidaurre CF. Omalizumab for the treatment of exacerbations in children with inadequately controlled allergic (IgE-mediated) asthma. J Allergy Clin Immunol. 2009 Dec;124(6):1210-6.

Responsible Party:	External Affairs, Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT00079937 History of Changes
Other Study ID Numbers:	CIGE025AIA05
Study First Received:	March 18, 2004
Results First Received:	December 3, 2010
Last Updated:	July 7, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Novartis:

allergic
asthma
atopic
omalizumab

immunoglobulin E
IgE
anti-IgE

Additional relevant MeSH terms:

Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Fluticasone
Omalizumab

Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Dermatologic Agents
Anti-Allergic Agents
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on February 12, 2012