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

NCT00079937 | Completed Phase 3 Results

• 1 other identifier: CIGE025AIA05
• Study Type: interventional
• Target: 628
• Locations: 1 country
• Sites: 56

Brief 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.

Conditions

Asthma

Keywords

allergic; asthma; atopic; omalizumab; immunoglobulin E; IgE; anti-IgE

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• Change in Mean Nocturnal Asthma Symptom Score From Baseline to the End (Last 4 Weeks) of the 24-week Fixed-dose Steroid Treatment Period

  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

  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

  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)

  Baseline to the end of the 24-week fixed-dose steroid treatment period (Week 24)

Study Arms (2)

Omalizumab

EXPERIMENTAL

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; Drug: Fluticasone

Placebo

PLACEBO COMPARATOR

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; Drug: Fluticasone

Interventions

Omalizumab DRUG

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.

Omalizumab

Placebo DRUG

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

Placebo

Fluticasone DRUG

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.

Omalizumab; Placebo

Eligibility Criteria

• Age: 6 Years - 11 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (56)

Alabama Allergy and Asthma Center

Birmingham, Alabama, 35209, United States

Location

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72202, United States

Location

Clinical Research Center

Little Rock, Arkansas, 72205, United States

Location

Allergy and Asthma Specialists Medical Group

Huntington Beach, California, 92647, United States

Location

Pediatric Care and Medical Group

Huntington Beach, California, 92647, United States

Location

West Coast Clinical Trials

Long Beach, California, 90806, United States

Location

Southern California Research Center

Mission Viejo, California, 92691, United States

Location

Children's Hosptial of Orange County, Div Asthma, Allergy & Immunology

Orange, California, 92868, United States

Location

CA Allergy & Asthma Med Group

Palmdale, California, 93551, United States

Location

Dr. Joann Blessing-Moore

Palo Alto, California, 94304, United States

Location

Integrated Research Group

Riverside, California, 92506, United States

Location

Allergy Associates Medical Group

San Diego, California, 92120, United States

Location

Allergy and Asthma Medical Group & Research Center

San Diego, California, 92123, United States

Location

Allergy and Asthma Associates of Santa Clara Valley RC

San Jose, California, 95117, United States

Location

1304 15th St

Santa Monica, California, 90404, United States

Location

Bensch Research Associates

Stockton, California, 95207, United States

Location

Allergy & Asthma Med Group of Diablo Valley CR

Walnut Creek, California, 94598, United States

Location

National Jewish Medical and Research Center

Denver, Colorado, 80206, United States

Location

Miami Children's Hospital

Miami, Florida, 33155, United States

Location

Georgia Pollens

Albany, Georgia, 31707, United States

Location

Family Allergy and Asthma Center, PC

Atlanta, Georgia, 30342, United States

Location

Aeroallergy Research Labs of Savannah, Inc

Savannah, Georgia, 31406, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Asthma & Allergy Center

Elliott, Maryland, 21042, United States

Location

Northeast Med Research Associates

North Dartmouth, Massachusetts, 02747, United States

Location

St. Louis University School of Medicine

St Louis, Missouri, 63104, United States

Location

Midwest Allergy & Asthma Clinic

Omaha, Nebraska, 68114, United States

Location

Ocean Allergy & Respiratory Research Center

Brick, New Jersey, 08724, United States

Location

UMDNJ

Newark, New Jersey, 07101, United States

Location

Womes And childrens Hospital of Buffalo

Buffalo, New York, 14222, United States

Location

Asthma & Allergy Associates

Ithaca, New York, 14850, United States

Location

Allergy and Asthma Diagnostic Office

Liverpool, New York, 13088, United States

Location

Island Medical Research (Allergy and Asthma Center)

Rockville Centre, New York, 11570, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Allergy & Asthma Center of North carolina

High Point, North Carolina, 27262, United States

Location

Bernstein Clinical Research Center

Cincinnati, Ohio, 45231, United States

Location

Resp Dis of Children and Adolescents

Oklahoma City, Oklahoma, 73112, United States

Location

Clinical Research Institute of Southern Oregon

Medford, Oregon, 97504, United States

Location

501 Howard Av

Altoona, Pennsylvania, 16601, United States

Location

West Penn Allegheny General Health System

Pittsburgh, Pennsylvania, 15212, United States

Location

Asthma and Allergy Associates

Upland, Pennsylvania, 19013, United States

Location

AAPRI Clinical Research Institute

Lincoln, Rhode Island, 02865, United States

Location

Allergy Assoc., The ASthma, Allergy & Sinus Ctr

Knoxville, Tennessee, 37922, United States

Location

Vanderbilt University

Nashville, Tennessee, 37203, United States

Location

Pediatric Allergy/Immunology Associates, PA

Dallas, Texas, 75230, United States

Location

Pediatric Pulmonary Association of North Texas

Dallas, Texas, 75230, United States

Location

North Texas Institute for Clinical Trials

Fort Worth, Texas, 76132, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

7707 Fannin/Ste. 195

Houston, Texas, 77054, United States

Location

Sylvanna Research

San Antonio, Texas, 78229, United States

Location

Copperview Medical Center

South Jordan, Utah, 84095, United States

Location

Childrens Hospital of the Kings Daughters

Norfolk, Virginia, 23507, United States

Location

Virgina Commonwealth

Richmond, Virginia, 23219, United States

Location

A.S.T.H.M.A., Inc.

Seattle, Washington, 98105, United States

Location

508 W 6th Av

Spokane, Washington, 99204, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (5)

• Fiocchi A, Chinthrajah RS, Ansotegui IJ, Sriaroon P, Mustafa SS, Raut P, Cameron B, Gupta S, Fleischer DM. Does Comorbid Food Allergy Affect Response to Omalizumab in Patients with Asthma? J Asthma Allergy. 2024 Sep 17;17:889-900. doi: 10.2147/JAA.S475517. eCollection 2024.

  PMID: 39309477 DERIVED

• Witonsky J, Elhawary JR, Millette LA, Holweg CTJ, Ko J, Raut P, Borrell LN. Similar response to omalizumab in children with allergic asthma from different racial backgrounds. J Allergy Clin Immunol Pract. 2023 Sep;11(9):2911-2913. doi: 10.1016/j.jaip.2023.03.055. Epub 2023 Apr 23. No abstract available.

  PMID: 37088376 DERIVED

• 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.

  PMID: 33223095 DERIVED

• 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.

  PMID: 32298853 DERIVED

• 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.

  PMID: 19910033 DERIVED

MeSH Terms

Conditions

Asthma

Interventions

Omalizumab; Fluticasone

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; Androstadienes; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2004
• First Posted: March 22, 2004
• Study Start: April 1, 2004
• Primary Completion: March 1, 2008
• Study Completion: March 1, 2008
• Last Updated: April 11, 2012
• Results First Posted: August 3, 2011

Record last verified: 2012-04

Locations

US (56)