Preventative Omalizumab or Step-up Therapy for Severe Fall Exacerbations (PROSE)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Inner City Asthma Consortium (ICAC)
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT01430403
First received: September 1, 2011
Last updated: September 11, 2013
Last verified: September 2013
  Purpose

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." 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.


Condition Intervention Phase
Asthma
Biological: Omalizumab
Drug: Fluticasone
Biological: Placebo omalizumab
Biological: Placebo fluticasone
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Preventative Omalizumab or Step-up Therapy for Severe Fall Exacerbations (ICAC-20)

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Occurrence of one or more asthma exacerbations [ Time Frame: 4-5 months ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Virus-induced exacerbations as measured by an exacerbation that is associated with a virus detected using the nasal mucus samples. [ Time Frame: 4-5 month ] [ Designated as safety issue: Yes ]
  • Severity of asthma symptoms associated with a viral infection [ Time Frame: 4-5 months ] [ Designated as safety issue: Yes ]
    defined as the highest value among the following 3 variables: number of days with wheezing, tightness in the chest, or cough; number of nights with disturbed sleep as a result of asthma; and number of days on which the participant had to slow down or discontinue play/physical activities over a two-week period

  • Number of exacerbations evaluated monthly with and without viral respiratory infections [ Time Frame: 4-5 months ] [ Designated as safety issue: Yes ]
  • Composite Asthma Severity Index [ Time Frame: 4-5 months ] [ Designated as safety issue: No ]
  • Spirometry measurements [ Time Frame: 4-5 months ] [ Designated as safety issue: No ]
  • Asthma control measurements [ Time Frame: 4-5 months ] [ Designated as safety issue: No ]
    Measurements based on scores obtained from Asthma Control Test (ACT) and Childhood Asthma Control Test (CACT)questionnaire

  • Economic outcomes [ Time Frame: 4-5 months ] [ Designated as safety issue: No ]
  • School absences [ Time Frame: 4-5 months ] [ Designated as safety issue: No ]
  • Estimates of treatment adherence [ Time Frame: 4-5 months ] [ Designated as safety issue: No ]
  • Safety data (adverse events and serious adverse events) [ Time Frame: 4-5 months ] [ Designated as safety issue: No ]
  • Home allergen levels [ Time Frame: 4-5 months ] [ Designated as safety issue: No ]

Enrollment: 494
Study Start Date: September 2011
Estimated Study Completion Date: March 2014
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Omalizumab
Participants will receive active omalizumab (Xolair®) injections and a placebo 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. All participants will receive standardized specialist asthma care.
Biological: Omalizumab
Other Name: Xolair®
Biological: Placebo fluticasone
Each placebo blister for fluticasone will contain 13mg fill of lactose powder.
Other Name: Placebo Flovent® Diskus®
Experimental: Inhaled corticosteroid boost therapy (ICS)
Participants in the Inhaled Corticosteroid (ICS) boost arm will receive active ICS and placebo injections of omalizumab (Xolair®). Self-administered fluticasone (Flovent ® Diskus) inhalers sufficient to deliver the required 200 mcg or 500 mcg daily boost of fluticasone will used. All participants will receive standardized specialist asthma care.
Drug: Fluticasone
Other Name: Flovent® Diskus®
Biological: Placebo omalizumab
The composition of the placebo omalizumab is the same as the active study drug without the omalizumab.
Other Name: Placebo Xolair®
Placebo Comparator: Placebo
The placebo group will receive placebo injection and placebo inhaler. All participants will receive standardized specialist asthma care.
Biological: Placebo omalizumab
The composition of the placebo omalizumab is the same as the active study drug without the omalizumab.
Other Name: Placebo Xolair®
Biological: Placebo fluticasone
Each placebo blister for fluticasone will contain 13mg fill of lactose powder.
Other Name: Placebo Flovent® Diskus®

  Eligibility

Ages Eligible for Study:   6 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • combined body weight (as measured at the screening visit) and total serum IgE (immunoglobulin E) 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 100mcg fluticasone 100 mcg twice a day or equivalent at the Assumption of Care Visit and meet at least one of the following criteria: i. One or more asthma-related exacerbations, separated by at least two weeks, requiring treatment with a systemic corticosteroid course in the previous 12 months.

ii. One or more 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 received the chickenpox vaccine.
  • insurance which covers costs of medications.
  • have not used and do not plan to restart the following medications in the 7 days prior to the first visit: tricyclic antidepressants, ketaconazole, or beta adrenergic blocker drugs (both oral and 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 100mcg 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 counts less than 100 x 109/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.
  • live with a foster parent; not applicable if participant is able to provide consent.
  • do not have access to a phone (needed for scheduling appointments).
  • plan to move from the area during the study period.
  • have previously been treated with omalizumab (Xolair®) within 1 year of recruitment.
  • currently receiving or have received hyposensitization therapy to any allergen in the past year prior to recruitment.
  • received hyposensitization therapy to dust mite, Alternaria or cockroach for ≥ 6 months in the past 3 years prior to Recruitment.
  • 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.
  • Who 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 Johns Wort; 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.
  • Who were enrolled in the previous ICAC trial, Inner-City Anti-IgE (immunoglobulin E) Therapy for Asthma (ICATA,ICAC-08/09).
  • 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 Willebrands 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).
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01430403

Locations
United States, Colorado
National Jewish Health
Denver, Colorado, United States, 80206
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010
United States, Illinois
Children's Memorial Hospital - Department of Allergy
Chicago, Illinois, United States, 60614-3363
United States, Massachusetts
Boston University School of Medicine
Boston, Massachusetts, United States, 02118
United States, Michigan
Henry Ford Health System
Detroit, Michigan, United States, 48202
United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
United States, Ohio
Cincinnati Children's Hospital
Cincinnati, Ohio, United States, 45229
United States, Texas
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75235
Sponsors and Collaborators
Inner City Asthma Consortium (ICAC)
Investigators
Study Chair: Stanley Szefler, MD National Jewish Health
Study Chair: Stephen Teach, MD, MPH Children's Research Institute
  More Information

Additional Information:
No publications provided

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01430403     History of Changes
Other Study ID Numbers: DAIT ICAC-20
Study First Received: September 1, 2011
Last Updated: September 11, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Xolair
Omalizumab
Fluticasone
Flovent® Diskus®
Inhaled Corticosteroid Therapy
Anti-IgE Therapy
Anti-immunoglobulin E Therapy

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Immunoglobulin E
Immunoglobulins
Fluticasone
Omalizumab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Dermatologic Agents
Anti-Allergic Agents
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on April 16, 2014