Preventative Omalizumab or Step-up Therapy for Severe Fall Exacerbations

NCT01430403 | Completed Phase 4 Results DMC

• 1 other identifier: DAIT ICAC-20
• Study Type: interventional
• Target: 478
• Locations: 1 country
• Sites: 8

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.

Conditions

Asthma

Keywords

persistent allergic asthma; asthma exacerbations reduction; Xolair® (omalizumab); Flovent® Diskus® (fluticasone); placebo; inhaled corticosteroid therapy; anti-immunoglobulin E therapy; anti-IgE therapy

Outcome Measures

Primary Outcomes (2)

• Occurrence of One or More Asthma Exacerbations (All Treatment Steps [Steps 2-5])

  Asthma exacerbation defined as a prescribed course of systemic steroids by a clinician or initiation of a course of systemic steroids by a participant or a hospitalization during the fall outcome period (90 day period beginning on the first day of the participant's school year) to prevent a serious asthma outcome. If a participant initiates and completes a course of systemic steroids without clinician involvement, this course will be counted only if it meets the following minimum dosage: prednisone, prednisolone, or methylprednisolone at ≥ 20mg per day for 3 of any 5 consecutive days; or dexamethasone at ≥10mg per day for ≥1 day. Odds ratio comparing Placebo and Omalizumab arms across all treatment steps (Steps 2-5).

  90 Day outcome period

• Occurrence of One or More Asthma Exacerbations (Treatment Steps 2-4)

  Asthma exacerbation defined as a prescription of a course of systemic steroids by a clinician or initiation of a course of systemic steroids by a participant or a hospitalization during the fall outcome period (90 day period beginning on the first day of the participant's school year) to prevent a serious asthma outcome. If a participant initiates and completes a course of systemic steroids without clinician involvement, this course will be counted only if it meets the following minimum dosage: prednisone, prednisolone, or methylprednisolone at ≥20mg per day for 3 of any 5 consecutive days; or dexamethasone at ≥10mg per day for ≥1 day. Odds ratio comparing Inhaled corticosteroid boost therapy (ICS) and Omalizumab arms at Treatment Steps 2-4.

  90 Day outcome period

Secondary Outcomes (20)

• Virus-induced Exacerbations as Measured by an Exacerbation That is Associated With a Virus Detected Using the Nasal Mucus Samples

  90 Day outcome period

• Severity of Asthma Symptoms Associated With a Viral Infection:Omalizumab vs. Placebo

  90 Day outcome period

• Number of Exacerbations Evaluated Monthly With Viral Respiratory Infections: Omalizumab vs. Placebo

  90 Day outcome period

• Composite Asthma Severity Index (CASI), Treatment Steps 2-5: Omalizumab vs. Placebo

  90 Day outcome period

• Composite Asthma Severity Index (CASI), Treatment Steps 2-4: Omalizumab vs. ICS

  90 Day outcome period

Study Arms (3)

Omalizumab

EXPERIMENTAL

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.

Biological: Omalizumab; Biological: Placebo fluticasone

Inhaled Corticosteroid Boost Therapy (ICS)

EXPERIMENTAL

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.

Drug: Inhaled Corticosteroid Boost Therapy (ICS); Biological: Placebo omalizumab

Placebo

PLACEBO COMPARATOR

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

Biological: Placebo omalizumab; Biological: Placebo fluticasone

Interventions

Omalizumab 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.

Also known as: Xolair®

Omalizumab

Inhaled Corticosteroid Boost Therapy (ICS) 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.

Also known as: Flovent® Diskus®

Inhaled Corticosteroid Boost Therapy (ICS)

Placebo omalizumab 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.

Also known as: Placebo Xolair®

Inhaled Corticosteroid Boost Therapy (ICS); Placebo

Placebo fluticasone 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.

Also known as: Placebo Flovent® Diskus®

Omalizumab; Placebo

Eligibility Criteria

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

You may qualify if:

• 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).

You may not qualify if:

• 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;

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Inner-City Asthma Consortium: collaborator

Study Sites (8)

National Jewish Health

Denver, Colorado, 80206, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Children's Memorial Hospital - Department of Allergy

Chicago, Illinois, 60614-3363, United States

Location

Boston University School of Medicine

Boston, Massachusetts, 02118, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Cincinnati Children's Hospital

Cincinnati, Ohio, 45229, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75235, United States

Location

Related Publications (3)

• 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.

  PMID: 26518090 RESULT

• 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

• 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.

  PMID: 28608756 DERIVED

Related Links

• Division of Allergy, Immunology, and Transplantation (DAIT) website
• National Institute of Allergy and Infectious Diseases (NIAID) website
• Inner City Asthma Consortium (ICAC) Description and Goals

MeSH Terms

Conditions

Asthma

Interventions

Omalizumab

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

Results Point of Contact

• Title: Director, Clinical Research Operations Program
• Organization: DAIT/NIAID

DAITClinicalTrialsGov@niaid.nih.gov

301-594-7669

Study Officials

• Stanley Szefler, MD

  National Jewish Health

  STUDY CHAIR

• Stephen Teach, MD, MPH

  Children's National Research Institute

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2011
• First Posted: September 8, 2011
• Study Start: September 1, 2011
• Primary Completion: December 1, 2013
• Study Completion: March 1, 2014
• Last Updated: May 30, 2017
• Results First Posted: September 16, 2015

Record last verified: 2017-05

Locations

US (8)