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

Asthma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00079937
• Other study ID #: CIGE025AIA05
• Status: Completed
• Phase: Phase 3
• First received: March 18, 2004
• Last updated: April 9, 2012
• Start date: April 2004
• Est. completion date: March 2008

Study information

• Verified date: April 2012
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 628
• Est. completion date: March 2008
• Est. primary completion date: March 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 6 Years to 11 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Asthma

Intervention

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

Locations

Country	Name	City	State
United States	Georgia Pollens	Albany	Georgia
United States	501 Howard Av	Altoona	Pennsylvania
United States	Family Allergy and Asthma Center, PC	Atlanta	Georgia
United States	Alabama Allergy and Asthma Center	Birmingham	Alabama
United States	Ocean Allergy & Respiratory Research Center	Brick	New Jersey
United States	Womes And childrens Hospital of Buffalo	Buffalo	New York
United States	Rush University Medical Center	Chicago	Illinois
United States	Bernstein Clinical Research Center	Cincinnati	Ohio
United States	Pediatric Allergy/Immunology Associates, PA	Dallas	Texas
United States	Pediatric Pulmonary Association of North Texas	Dallas	Texas
United States	National Jewish Medical and Research Center	Denver	Colorado
United States	Duke University Medical Center	Durham	North Carolina
United States	Asthma & Allergy Center	Elliott City	Maryland
United States	North Texas Institute for Clinical Trials	Ft. Worth	Texas
United States	Allergy & Asthma Center of North carolina	High Point	North Carolina
United States	7707 Fannin/Ste. 195	Houston	Texas
United States	Baylor College of Medicine	Houston	Texas
United States	Allergy and Asthma Specialists Medical Group	Huntington Beach	California
United States	Pediatric Care and Medical Group	Huntington Beach	California
United States	Asthma & Allergy Associates	Ithaca	New York
United States	Allergy Assoc., The ASthma, Allergy & Sinus Ctr	Knoxville	Tennessee
United States	AAPRI Clinical Research Institute	Lincoln	Rhode Island
United States	Clinical Research Center	Little Rock	Arkansas
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Allergy and Asthma Diagnostic Office	Liverpool	New York
United States	West Coast Clinical Trials	Long Beach	California
United States	Clinical Research Institute of Southern Oregon	Medford	Oregon
United States	Miami Children's Hospital	Miami	Florida
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Southern California Research Center	Mission Viejo	California
United States	Vanderbilt University	Nashville	Tennessee
United States	UMDNJ	Newark	New Jersey
United States	Childrens Hospital of the Kings Daughters	Norfolk	Virginia
United States	Northeast Med Research Associates	North Dartmouth	Massachusetts
United States	Resp Dis of Children and Adolescents	Oklahoma City	Oklahoma
United States	Midwest Allergy & Asthma Clinic	Omaha	Nebraska
United States	Children's Hosptial of Orange County, Div Asthma, Allergy & Immunology	Orange	California
United States	CA Allergy & Asthma Med Group	Palmdale	California
United States	Dr. Joann Blessing-Moore	Palo Alto	California
United States	West Penn Allegheny General Health System	Pittsburgh	Pennsylvania
United States	Virgina Commonwealth	Richmond	Virginia
United States	Integrated Research Group	Riverside	California
United States	Island Medical Research (Allergy and Asthma Center)	Rockville Center	New York
United States	Sylvanna Research	San Antonio	Texas
United States	Allergy and Asthma Medical Group & Research Center	San Diego	California
United States	Allergy Associates Medical Group	San Diego	California
United States	Allergy and Asthma Associates of Santa Clara Valley RC	San Jose	California
United States	1304 15th St	Santa Monica	California
United States	Aeroallergy Research Labs of Savannah, Inc	Savannah	Georgia
United States	A.S.T.H.M.A., Inc.	Seattle	Washington
United States	Copperview Medical Center	South Jordan	Utah
United States	508 W 6th Av	Spokane	Washington
United States	St. Louis University School of Medicine	St. Louis	Missouri
United States	Bensch Research Associates	Stockton	California
United States	Asthma and Allergy Associates	Upland	Pennsylvania
United States	Allergy & Asthma Med Group of Diablo Valley CR	Walnut Creek	California

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of Clinically Significant Asthma Exacerbations Per Patient in the 24-week Fixed-dose Steroid Treatment Period	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.	Baseline to end of the fixed-dose steroid treatment period (Week 24)	No
Primary	Percentage of Participants With at Least 1 Adverse Event	See Adverse Events module for details.	Baseline to end of the study (Week 68)	Yes
Secondary	Change in Mean Nocturnal Asthma Symptom Score From Baseline to the End (Last 4 Weeks) of the 24-week Fixed-dose Steroid Treatment Period	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 negative change in mean score indicated improvement.	Baseline to the end (last 4 weeks) of the 24-week fixed-dose steroid treatment period	No
Secondary	Rate of Clinically Significant Asthma Exacerbations Per Patient in the 52-week Treatment Period	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.	Baseline to end of the treatment period (Week 52)	No
Secondary	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	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 negative change in mean daily number of puffs indicated reduced use of rescue medication.	Baseline to the end (last 4 weeks) of the 24-week fixed-dose steroid treatment period	No
Secondary	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)	PAQLQ measures functional problems that are most troublesome to children with asthma. PAQLQ has 23 questions in 3 domains (activity limitation=5, emotional function=8, symptoms=10). Patients responded to each question on a 7-point Likert scale. Overall PAQLQ score is mean of 23 questions; each domain score is mean of questions in that domain. Minimum possible value is 1 (maximum impairment); maximum possible value is 7 (no impairment). Positive change indicated improvement. The analysis included country, baseline PAQLQ value, and dosing schedule (2-weekly/4-weekly) as factors and covariates.	Baseline to the end of the 24-week fixed-dose steroid treatment period (Week 24)	No