Preventative Omalizumab or Step-up Therapy for Severe Fall Exacerbations

NCT ID: NCT01430403

Last Updated: 2017-05-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 478 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-09-30
• Study Completion Date: 2014-03-31

Brief Summary

The purpose of this trial is to compare the efficacy of 4 to 5 months of three treatments - omalizumab, corticosteroid therapy boost, and placebo - in reducing fall exacerbations in inner-city children and adolescents with allergic persistent asthma when initiated approximately 4 -6 weeks prior to the start of the first day of each participant's school year.

Detailed Description

While the increase in the prevalence of asthma has abated, levels of asthma morbidity and mortality remain near record highs. An asthma exacerbation is a major factor contributing to morbidity, and even mortality in patients with asthma. Although current approaches to treatment have reduced these risks, asthma exacerbations are major problems for inner-city patients and their families, and prevention of these events continues to be a significant challenge. In children with asthma, there are predictable seasonal epidemics of exacerbations, especially during the fall season, otherwise known as the "September epidemic."

Conditions

Asthma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Omalizumab

Participants receive active omalizumab (Xolair®) injections and a placebo Flovent® Diskus® (fluticasone) inhaler. Each participant will receive omalizumab (Xolair®) subcutaneous injections at minimum dose of 0.016 mg/kg/IgE (immunoglobulin E) \[IU/mL\] every 2 or 4 weeks during the 4-5 months treatment period. In addition, all participants receive standardized specialist asthma care.

Group Type: EXPERIMENTAL

Omalizumab

Intervention Type: BIOLOGICAL

Participants received active omalizumab (Xolair(R)) injections and a placebo inhaler. Each participant received omalizumab (Xolair(R)) subcutaneous injections at minimum dose of 0.016 mg/kg/IgE (immunoglobulin E) \[IU/mL\] every 2 or 4 weeks during the 4-5 months treatment period. All participants received standardized specialist asthma care.

Placebo fluticasone

Intervention Type: BIOLOGICAL

Self-administered placebo fluticasone (placebo Flovent ® Diskus®) inhalers identical in dose and guidance as active fluticasone. All participants will receive standardized specialist asthma care.

Inhaled Corticosteroid Boost Therapy (ICS)

Participants in this group, the Inhaled Corticosteroid (ICS) boost arm, receive active ICS and placebo omalizumab (Xolair®) injections. Self-administered fluticasone (Flovent ® Diskus®) inhalers sufficient to deliver the required 200 mcg or 500 mcg daily boost of fluticasone will be used. In addition, all participants receive standardized specialist asthma care.

Group Type: EXPERIMENTAL

Inhaled Corticosteroid Boost Therapy (ICS)

Intervention Type: DRUG

Self-administered fluticasone (Flovent ® Diskus®) inhalers sufficient to deliver the required 200 mcg or 500 mcg daily boost of fluticasone. All participants will receive standardized specialist asthma care.

Placebo omalizumab

Intervention Type: BIOLOGICAL

Placebo was administered subcutaneously every 2 or 4 weeks over a period of 4 to 5 months. Doses (mg) and dosing frequency were determined by serum total immunoglobulin E (IgE) level (IU/mL) and body weight (kg). Also, participants continued with their conventional asthma therapy according to the National Asthma Education and Prevention Program (NAEPP, 2007) guidelines, under the management of an asthma specialist health care provider.

Placebo

The placebo group receive placebo omalizumab (Xolair®) injections and placebo Flovent® Diskus® (fluticasone) inhaler. In addition, all participants receive standardized specialist asthma care.

Group Type: PLACEBO_COMPARATOR

Placebo omalizumab

Intervention Type: BIOLOGICAL

Placebo was administered subcutaneously every 2 or 4 weeks over a period of 4 to 5 months. Doses (mg) and dosing frequency were determined by serum total immunoglobulin E (IgE) level (IU/mL) and body weight (kg). Also, participants continued with their conventional asthma therapy according to the National Asthma Education and Prevention Program (NAEPP, 2007) guidelines, under the management of an asthma specialist health care provider.

Placebo fluticasone

Intervention Type: BIOLOGICAL

Self-administered placebo fluticasone (placebo Flovent ® Diskus®) inhalers identical in dose and guidance as active fluticasone. All participants will receive standardized specialist asthma care.

Interventions

Omalizumab

Participants received active omalizumab (Xolair(R)) injections and a placebo inhaler. Each participant received omalizumab (Xolair(R)) subcutaneous injections at minimum dose of 0.016 mg/kg/IgE (immunoglobulin E) \[IU/mL\] every 2 or 4 weeks during the 4-5 months treatment period. All participants received standardized specialist asthma care.

Intervention Type: BIOLOGICAL

Inhaled Corticosteroid Boost Therapy (ICS)

Self-administered fluticasone (Flovent ® Diskus®) inhalers sufficient to deliver the required 200 mcg or 500 mcg daily boost of fluticasone. All participants will receive standardized specialist asthma care.

Intervention Type: DRUG

Placebo omalizumab

Placebo was administered subcutaneously every 2 or 4 weeks over a period of 4 to 5 months. Doses (mg) and dosing frequency were determined by serum total immunoglobulin E (IgE) level (IU/mL) and body weight (kg). Also, participants continued with their conventional asthma therapy according to the National Asthma Education and Prevention Program (NAEPP, 2007) guidelines, under the management of an asthma specialist health care provider.

Intervention Type: BIOLOGICAL

Placebo fluticasone

Self-administered placebo fluticasone (placebo Flovent ® Diskus®) inhalers identical in dose and guidance as active fluticasone. All participants will receive standardized specialist asthma care.

Intervention Type: BIOLOGICAL

Other Intervention Names

Xolair®; Flovent® Diskus®; Placebo Xolair®; Placebo Flovent® Diskus®

Eligibility Criteria

Inclusion Criteria

• Combined body weight (as measured at the screening visit) and total serum IgE level (as measured within 3 months of the screening visit) suitable for omalizumab (Xolair®) dosing;
• A diagnosis of asthma by a clinician made more than 1 year prior to recruitment; participants who received an asthma diagnosis by a clinician less than 1 year prior to recruitment must report that their respiratory symptoms were present for more than 1 year prior to recruitment;
• Having a requirement for at least 100 mcg fluticasone 100 mcg twice a day or equivalent at the Assumption of Care Visit AND who meet at least one of the following criteria:

i. ≥1 asthma-related exacerbations, separated by at least two weeks, requiring treatment with a systemic corticosteroid course in the previous 12 months ii. ≥1 asthma-related overnight hospitalizations in the past 12 months.

• A positive prick skin-test to at least one perennial allergen (i.e. dust mite, cockroach, mold, cat, dog, rat, mouse) documented at the screening visit or at a ICAC study visit within 12 months of the screening visit;
• Primary place of residence is in one of the pre-selected recruitment census tracts;
• Able to perform spirometry;
• Parent or legal guardian is willing to sign the written informed consent (age appropriate) prior to initiation of any study procedure;
• Willing to sign the assent form, if age appropriate;
• A history of chickenpox or receipt of the chickenpox vaccine;
• Insurance which covers costs of medications; and
• Have not used and do not plan to restart any of the following medications in the 7 days prior to the first visit: tricyclic antidepressants, ketaconazole, or beta adrenergic blocker drugs (oral and/or topical).

Exclusion Criteria

Participants who meet any of the following criteria are not eligible for enrollment but may be reassessed:

• Assigned to a treatment of less than 100 mcg fluticasone twice a day or equivalent at the Assumption of Care Visit;
• Pregnant or lactating. Females of child-bearing potential (post-menarche) must be abstinent or use a medically acceptable birth control method throughout the study (e.g. oral, subcutaneous, mechanical, or surgical contraception);
• Clinically significant laboratory abnormalities (not associated with the study indication) at the screening visit;
• Platelet count less than 100 x 10^9/L at the screening visit;
• Currently participating in another asthma-related pharmaceutical study or intervention study or who have participated in another asthma-related pharmaceutical study or intervention study in the month prior to Recruitment;
• Living with a foster parent: exception -not applicable if participant is able to provide consent;
• Does not have access to a phone (needed for scheduling appointments);
• Plan(s) to move from the area during the study period;
• Has previously been treated with omalizumab (Xolair®) within 1 year of recruitment;
• Currently receiving or has received hyposensitization therapy to any allergen in the past year prior to recruitment;
• Has received hyposensitization therapy to dust mite, Alternaria or cockroach for ≥ 6 months in the past 3 years prior to Recruitment;
• Has experienced a life-threatening asthma exacerbation in the last 2 years requiring intubation, mechanical ventilation, or resulting in a hypoxic seizure;
• Home-schooled or in year round school;
• Are currently taking or who have taken any of the following medications within 4 weeks of the Screening Visit: monoamine oxidase inhibitors (phenelzine, tranylcypromine); tricyclic and tetracyclic antidepressants; beta adrenergic blocker drugs (both oral and topical); anticonvulsants(carbamazepine, phenobarbital, phenytoin, mephobarbital, primidone,ethosuximide, methsuximide, felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, tiagabine, topiramate, valproic acid, divalproex sodium, zonisamide); protease inhibitors(ritonavir, indinavir, nelfinavir); calcium channel blockers (verapamil, diltiazem); modafinil; tamoxifen; non-nucleoside reverse transcriptase inhibitors; macrolide antibiotics*(erythromycin, clarithromycin, dirithromycin, troleandomycin); chloramphenicol; nefazodone; aprepitant; St. John's Wort (hypericum); Rifampin*; Azole antifungals* (ketoconazole, fluconazole,itraconazole); Sibutramine*; bergamottin* (constituent of grapefruit juice).*may be rescreened if this therapy is short-lived;
• Will not allow the study clinician, an asthma specialist, to manage their disease for the duration of the study or who are not willing to change their asthma medications to follow the protocol.

Participants who meet any of the following criteria are not eligible for assumption of care and may not be reassessed except where noted:

• A current severe hypersensitivity to milk;
• Individuals who were enrolled in the previous ICAC trial, Inner-City Anti-IgE Therapy for Asthma (ICATA,ICAC-NCT00377572);
• Individuals who have any medical illnesses that in the opinion of the investigators would a.) increase the risk the subject would incur by participating in the study; b.) interfere with the measured outcomes of the study; or c.) interfere with the performance of the study procedures. Examples of such diseases are: cystic fibrosis, bronchiectasis, type 1 diabetes, hemophilia, Von Willebrand disease, sickle cell disease, cerebral palsy, rheumatoid arthritis, lupus, psoriasis, hyperimmunoglobulin E syndrome, parasite infections, Wiskott-Aldrich Syndrome or allergic bronchopulmonary aspergillosis.
• Known hypersensitivity to any ingredients, including excipients (sucrose, histidine, polysorbate 20) of the study medication or drugs related to omalizumab (e.g. monoclonal antibodies, polyclonal gamma globulin) or fluticasone;
• Currently have diagnosed cancer, are currently being investigated for possible cancer, or who have a history of cancer;
• Do not primarily speak English (or Spanish at centers with Spanish speaking staff)
• The participant's caretaker does not primarily speak English (or Spanish at centers with Spanish speaking staff); not applicable if participant is able to provide consent.
• A history of severe(grade 3) anaphylactoid or anaphylactic reaction(s).

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Inner-City Asthma Consortium

NETWORK

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stanley Szefler, MD

Role: STUDY_CHAIR

National Jewish Health

Stephen Teach, MD, MPH

Role: STUDY_CHAIR

Children's National Research Institute

Locations

National Jewish Health

Denver, Colorado, United States

Children's National Medical Center

Washington D.C., District of Columbia, United States

Children's Memorial Hospital - Department of Allergy

Chicago, Illinois, United States

Boston University School of Medicine

Boston, Massachusetts, United States

Henry Ford Health System

Detroit, Michigan, United States

Columbia University Medical Center

New York, New York, United States

Cincinnati Children's Hospital

Cincinnati, Ohio, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Countries

United States

References

Teach SJ, Gill MA, Togias A, Sorkness CA, Arbes SJ Jr, Calatroni A, Wildfire JJ, Gergen PJ, Cohen RT, Pongracic JA, Kercsmar CM, Khurana Hershey GK, Gruchalla RS, Liu AH, Zoratti EM, Kattan M, Grindle KA, Gern JE, Busse WW, Szefler SJ. Preseasonal treatment with either omalizumab or an inhaled corticosteroid boost to prevent fall asthma exacerbations. J Allergy Clin Immunol. 2015 Dec;136(6):1476-1485. doi: 10.1016/j.jaci.2015.09.008. Epub 2015 Oct 27.

Reference Type: RESULT

PMID: 26518090 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32298853 (View on PubMed)

Esquivel A, Busse WW, Calatroni A, Togias AG, Grindle KG, Bochkov YA, Gruchalla RS, Kattan M, Kercsmar CM, Khurana Hershey G, Kim H, Lebeau P, Liu AH, Szefler SJ, Teach SJ, West JB, Wildfire J, Pongracic JA, Gern JE. Effects of Omalizumab on Rhinovirus Infections, Illnesses, and Exacerbations of Asthma. Am J Respir Crit Care Med. 2017 Oct 15;196(8):985-992. doi: 10.1164/rccm.201701-0120OC.

Reference Type: DERIVED

PMID: 28608756 (View on PubMed)

Related Links

https://www.niaid.nih.gov/about/dait

Division of Allergy, Immunology, and Transplantation (DAIT) website

https://www.niaid.nih.gov/research/role

National Institute of Allergy and Infectious Diseases (NIAID) website

http://www.niaid.nih.gov/topics/asthma/research/Pages/innerCity.aspx#icac

Inner City Asthma Consortium (ICAC) Description and Goals

Other Identifiers

DAIT ICAC-20

Identifier Type: -

Identifier Source: org_study_id