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

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

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.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: Omalizumab; Drug: Fluticasone; Drug: Placebo

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).

• Study Type: Interventional
• Enrollment (Actual): 628
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • Alabama Allergy and Asthma Center
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • University of Arkansas for Medical Sciences
    • Little Rock, Arkansas, United States, 72205
      • Clinical Research Center
  • California
    • Huntington Beach, California, United States, 92647
      • Allergy and Asthma Specialists Medical Group
    • Huntington Beach, California, United States, 92647
      • Pediatric Care and Medical Group
    • Long Beach, California, United States, 90806
      • West Coast Clinical Trials
    • Mission Viejo, California, United States, 92691
      • Southern California Research Center
    • Orange, California, United States, 92868
      • Children's Hosptial of Orange County, Div Asthma, Allergy & Immunology
    • Palmdale, California, United States, 93551
      • CA Allergy & Asthma Med Group
    • Palo Alto, California, United States, 94304
      • Dr. Joann Blessing-Moore
    • Riverside, California, United States, 92506
      • Integrated Research Group
    • San Diego, California, United States, 92120
      • Allergy Associates Medical Group
    • San Diego, California, United States, 92123
      • Allergy and Asthma Medical Group & Research Center
    • San Jose, California, United States, 95117
      • Allergy and Asthma Associates of Santa Clara Valley RC
    • Santa Monica, California, United States, 90404
      • 1304 15th St
    • Stockton, California, United States, 95207
      • Bensch Research Associates
    • Walnut Creek, California, United States, 94598
      • Allergy & Asthma Med Group of Diablo Valley CR
  • Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Medical and Research Center
  • Florida
    • Miami, Florida, United States, 33155
      • Miami Children's Hospital
  • Georgia
    • Albany, Georgia, United States, 31707
      • Georgia Pollens
    • Atlanta, Georgia, United States, 30342
      • Family Allergy and Asthma Center, PC
    • Savannah, Georgia, United States, 31406
      • Aeroallergy Research Labs of Savannah, Inc
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
  • Maryland
    • Elliott City, Maryland, United States, 21042
      • Asthma & Allergy Center
  • Massachusetts
    • North Dartmouth, Massachusetts, United States, 02747
      • Northeast Med Research Associates
  • Missouri
    • St. Louis, Missouri, United States, 63104
      • St. Louis University School of Medicine
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Midwest Allergy & Asthma Clinic
  • New Jersey
    • Brick, New Jersey, United States, 08724
      • Ocean Allergy & Respiratory Research Center
    • Newark, New Jersey, United States, 07101
      • UMDNJ
  • New York
    • Buffalo, New York, United States, 14222
      • Womes And childrens Hospital of Buffalo
    • Ithaca, New York, United States, 14850
      • Asthma & Allergy Associates
    • Liverpool, New York, United States, 13088
      • Allergy and Asthma Diagnostic Office
    • Rockville Center, New York, United States, 11570
      • Island Medical Research (Allergy and Asthma Center)
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • High Point, North Carolina, United States, 27262
      • Allergy & Asthma Center of North carolina
  • Ohio
    • Cincinnati, Ohio, United States, 45231
      • Bernstein Clinical Research Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Resp Dis of Children and Adolescents
  • Oregon
    • Medford, Oregon, United States, 97504
      • Clinical Research Institute of Southern Oregon
  • Pennsylvania
    • Altoona, Pennsylvania, United States, 16601
      • 501 Howard Av
    • Pittsburgh, Pennsylvania, United States, 15212
      • West Penn Allegheny General Health System
    • Upland, Pennsylvania, United States, 19013
      • Asthma and Allergy Associates
  • Rhode Island
    • Lincoln, Rhode Island, United States, 02865
      • AAPRI Clinical Research Institute
  • Tennessee
    • Knoxville, Tennessee, United States, 37922
      • Allergy Assoc., The ASthma, Allergy & Sinus Ctr
    • Nashville, Tennessee, United States, 37203
      • Vanderbilt University
  • Texas
    • Dallas, Texas, United States, 75230
      • Pediatric Allergy/Immunology Associates, PA
    • Dallas, Texas, United States, 75230
      • Pediatric Pulmonary Association of North Texas
    • Ft. Worth, Texas, United States, 76132
      • North Texas Institute for Clinical Trials
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • Houston, Texas, United States, 77054
      • 7707 Fannin/Ste. 195
    • San Antonio, Texas, United States, 78229
      • Sylvanna Research
  • Utah
    • South Jordan, Utah, United States, 84095
      • Copperview Medical Center
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Childrens Hospital of The Kings Daughters
    • Richmond, Virginia, United States, 23219
      • Virgina Commonwealth
  • Washington
    • Seattle, Washington, United States, 98105
      • A.S.T.H.M.A., Inc.
    • Spokane, Washington, United States, 99204
      • 508 W 6th Av
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 11 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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: 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.; Drug: Placebo; Placebo was administered subcutaneous (SC) every 2 or 4 weeks depending on the dosing schedule in the protocol.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
Percentage of Participants With at Least 1 Adverse Event	See Adverse Events module for details.	Baseline to end of the study (Week 68)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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)
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
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)

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Szefler SJ, Casale TB, Haselkorn T, Yoo B, Ortiz B, Kattan M, Busse WW. Treatment Benefit with Omalizumab in Children by Indicators of Asthma Severity. J Allergy Clin Immunol Pract. 2020 Sep;8(8):2673-2680.e3. doi: 10.1016/j.jaip.2020.03.033. Epub 2020 Apr 13.
• Busse WW, Szefler SJ, Haselkorn T, Iqbal A, Ortiz B, Lanier BQ, Chipps BE. Possible Protective Effect of Omalizumab on Lung Function Decline in Patients Experiencing Asthma Exacerbations. J Allergy Clin Immunol Pract. 2021 Mar;9(3):1201-1211. doi: 10.1016/j.jaip.2020.10.027. Epub 2020 Oct 24.
• 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. doi: 10.1016/j.jaci.2009.09.021.

Study record dates

Study Major Dates

• Study Start: April 1, 2004
• Primary Completion (Actual): March 1, 2008
• Study Completion (Actual): March 1, 2008

Study Registration Dates

• First Submitted: March 18, 2004
• First Submitted That Met QC Criteria: March 19, 2004
• First Posted (Estimate): March 22, 2004

Study Record Updates

• Last Update Posted (Estimate): April 11, 2012
• Last Update Submitted That Met QC Criteria: April 9, 2012
• Last Verified: April 1, 2012

More Information

Terms related to this study

• Keywords: asthma; omalizumab; IgE; allergic; anti-IgE; immunoglobulin E; atopic
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Dermatologic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Anti-Allergic Agents; Fluticasone; Omalizumab
• Other Study ID Numbers: CIGE025AIA05