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

This study has been completed.
Sponsor:
Collaborator:
Inner-City Asthma Consortium
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT01430403
First received: September 1, 2011
Last updated: January 22, 2016
Last verified: January 2016
  Purpose
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+Conventional Therapy
Drug: Fluticasone+Conventional Therapy
Biological: Placebo omalizumab+Conventional Therapy
Biological: Placebo fluticasone+Conventional Therapy
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial 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 (All Treatment Steps [Steps 2-5]) [ Time Frame: 90 Day outcome period ] [ Designated as safety issue: Yes ]
    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).

  • Occurrence of One or More Asthma Exacerbations (Treatment Steps 2-4) [ Time Frame: 90 Day outcome period ] [ 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. Odds ratio comparing Inhaled corticosteroid boost therapy (ICS) and Omalizumab arms at Treatment Steps 2-4.


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 (CASI), Treatment Steps 2-5 (Omalizumab vs. Placebo) [ Time Frame: 90 Day outcome period ] [ Designated as safety issue: No ]
    CASI scores include 5 domains: day symptoms and albuterol use, night symptoms and albuterol use, controller treatment, lung function measures, and exacerbations. To calculate CASI, the 5 domain scores are summed to determine a final score, which can range from 0 to 20, with 0 being no severity of asthma and 20 being extremely severe asthma.

  • Composite Asthma Severity Index (CASI), Treatment Steps 2-4 (Omalizumab vs. ICS) [ Time Frame: 90 Day outcome period ] [ Designated as safety issue: No ]
    CASI scores include 5 domains: day symptoms and albuterol use, night symptoms and albuterol use, controller treatment, lung function measures, and exacerbations. To calculate CASI, the 5 domain scores are summed to determine a final score, which can range from 0 to 20, with 0 being no severity of asthma and 20 being extremely severe asthma.

  • Spirometry Measurements: Forced Expiratory Volume in 1 Second (FEV1) % Predicted, Treatment Steps 2-5 (Omalizumab vs. Placebo) [ Time Frame: 90 Day outcome period ] [ Designated as safety issue: No ]
    FEV1 is air volume exhaled in 1 second during spirometry. Asthma severity classification for trial: mild--pre-bronchodilator FEV1 ≥ 80% predicted requiring no/ low-moderate dose of inhaled glucocorticoids; moderate--pre-bronchodilator FEV1 <80% predicted requiring no/ low-moderate dose of inhaled glucocorticoids; severe--requiring high-dose inhaled glucocorticoids with/without continuous/near continuous oral glucocorticoids, or uncontrolled despite treatment. FEV1 percent of predicted value is FEV1 converted to a percentage of normal, based on height, weight, and race.

  • Spirometry Measurements: Forced Expiratory Volume in 1 Second (FEV1) % Predicted , Treatment Steps 2-4 (Omalizumab vs. ICS) [ Time Frame: 90 Day outcome period ] [ Designated as safety issue: No ]
    FEV1 is air volume exhaled in 1 second during spirometry. Asthma severity classification for trial: mild--pre-bronchodilator FEV1 ≥ 80% predicted requiring no/ low-moderate dose of inhaled glucocorticoids; moderate--pre-bronchodilator FEV1 <80% predicted requiring no/ low-moderate dose of inhaled glucocorticoids; severe--requiring high-dose inhaled glucocorticoids with/without continuous/near continuous oral glucocorticoids, or uncontrolled despite treatment. FEV1 percent of predicted value is FEV1 converted to a percentage of normal, based on height, weight, and race.

  • Spirometry Measurements: FEV1:FVCx100, Treatment Steps 2-5 (Omalizumab vs. Placebo) [ Time Frame: 90 Day outcome period ] [ Designated as safety issue: No ]
    The FEV1 (forced expiratory volume 1))/ FVC (forced vital capacity) ratio is used to evaluate airways obstructions since pure restrictive ventilatory defects cause an equal reduction in the FEV1 and the FVC. An FEV1/FVC ratio below 80% indicates airflow obstruction. Normal FEV1/FVC: 8 - 19 years of age=85%.

  • Spirometry Measurements: FEV1:FVCx100, Treatment Steps 2-4 (Omalizumab vs. ICS) [ Time Frame: 90 Day outcome period ] [ Designated as safety issue: No ]
    The FEV1 (forced expiratory volume 1))/ FVC (forced vital capacity) ratio is used to evaluate airways obstructions since pure restrictive ventilatory defects cause an equal reduction in the FEV1 and the FVC. An FEV1/FVC ratio below 80% indicates airflow obstruction. Normal FEV1/FVC: 8 - 19 years of age=85%.

  • Asthma Control Test Scores: Asthma Control Test (ACT), Treatment Steps 2-5 (Omalizumab vs. Placebo) [ Time Frame: 90 Day outcome period ] [ Designated as safety issue: No ]
    Outcome measure description: The Asthma Control Test (ACT) is a validated tool to assess asthma control (over the last 4 weeks) in patients >= 12 yrs old. It is comprised of 5 questions assessing symptoms, use of rescue medications, and the impact of asthma on everyday functioning. All questions are scored on a 5-point Likert scale (higher score indicating better control). Total scores can range from 5-25. A score of <= 19 is indicative of not well-controlled asthma. The minimally important difference is 3 points.

  • Asthma Control Test Scores: Asthma Control Test (ACT), Treatment Steps 2-4 (Omalizumab vs. ICS) [ Time Frame: 90 Day outcome period ] [ Designated as safety issue: No ]
    The Asthma Control Test (ACT) is a validated tool to assess asthma control (over the last 4 weeks) in patients >= 12 yrs old. It is comprised of 5 questions assessing symptoms, use of rescue medications, and the impact of asthma on everyday functioning. All questions are scored on a 5-point Likert scale (higher score indicating better control). Total scores can range from 5-25. A score of <= 19 is indicative of not well-controlled asthma. The minimally important difference is 3 points.

  • Asthma Control Test Score: Child Asthma Control Test (C-ACT), Treatment Steps 2-5 (Omalizumab vs. Placebo) [ Time Frame: 90 Day outcome period ] [ Designated as safety issue: No ]
    The Childhood Asthma Control Test (C-ACT) is a validated tool to assess overall asthma control (over the last 4 weeks) in patients ages 4 to 11 years. Scores can range from 0 to 27. A score of 19 or less is indicative of asthma that is not well controlled. The minimally important difference in C-ACT scores is not defined

  • Asthma Control Test Score: Child Asthma Control Test (C-ACT), Treatment Steps 2-4 (Omalizumab vs. ICS) [ Time Frame: 90 Day outcome period ] [ Designated as safety issue: No ]
    The Childhood Asthma Control Test (C-ACT) is a validated tool to assess overall asthma control (over the last 4 weeks) in patients ages 4 to 11 years. Scores can range from 0 to 27. A score of 19 or less is indicative of asthma that is not well controlled. The minimally important difference in C-ACT scores is not defined.

  • Work Disruptions Due to Child's Asthma, Treatment Steps 2-5 (Omalizumab vs. Placebo) [ Time Frame: 90 Day outcome period ] [ Designated as safety issue: No ]
    The ratio of the work hours missed due to child's asthma over the numbers of work hours in the past 14 days among caretakers working.

  • Work Disruptions Due to Child's Asthma, Treatment Steps 2-4 (Omalizumab vs. ICS) [ Time Frame: 90 Day outcome period ] [ Designated as safety issue: No ]
    The ratio of the work hours missed due to child's asthma over the numbers of work hours in the past 14 days among caretakers working

  • School Absences (Percent), Treatment Steps 2-5 (Omalizumab vs. Placebo) [ Time Frame: 90 Day outcome period ] [ Designated as safety issue: No ]
    The ratio of the number of school days missed over the numbers of school days in session

  • School Absences (Percent), Treatment Steps 2-4 (Omalizumab vs. ICS) [ Time Frame: 90 Day outcome period ] [ Designated as safety issue: No ]
    The ratio of the number of school days missed over the numbers of school days in session

  • Percent Adherence to Asthma Medication, Treatment Steps 2-5 (Omalizumab vs. Placebo) [ Time Frame: 90 Day outcome period ] [ Designated as safety issue: No ]
    Adherence to the study regimen and other asthma treatments, assessed as percent of expected dose taken, by means of study interviews and study physician corroboration.

  • Percent Adherence to Asthma Medication, Treatment Steps 2-4 (Omalizumab vs. ICS) [ Time Frame: 90 Day outcome period ] [ Designated as safety issue: No ]
    Adherence to the study regimen and other asthma treatments, assessed as percent of expected dose taken, by means of study interviews and study physician corroboration.

  • Home Allergen Levels [ Time Frame: 4-5 months ] [ Designated as safety issue: No ]

Enrollment: 478
Study Start Date: September 2011
Study Completion Date: March 2014
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Omalizumab+Conventional Therapy
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+Conventional Therapy
Omalizumab 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.
Other Name: Xolair®
Biological: Placebo fluticasone+Conventional Therapy
Self-administered placebo fluticasone (placebo Flovent ® Diskus®) inhalers identical in dose and guidance as active fluticasone. All participants will receive standardized specialist asthma care.
Other Name: Placebo Flovent® Diskus®
Experimental: Fluticasone+Conventional Therapy
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: Fluticasone+Conventional Therapy
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.
Other Name: Flovent® Diskus®
Biological: Placebo omalizumab+Conventional Therapy
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.
Other Name: Placebo Xolair®
Placebo Comparator: Placebo+Conventional Therapy
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+Conventional Therapy
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.
Other Name: Placebo Xolair®
Biological: Placebo fluticasone+Conventional Therapy
Self-administered placebo fluticasone (placebo Flovent ® Diskus®) inhalers identical in dose and guidance as active fluticasone. All participants will receive standardized specialist asthma care.
Other Name: Placebo Flovent® Diskus®

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."
  Eligibility

Ages Eligible for Study:   6 Years to 17 Years   (Child)
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 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
  • 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 10E9/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
  • who were enrolled in the previous ICAC trial, Inner-City Anti-IgE 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 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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
National Institute of Allergy and Infectious Diseases (NIAID)
Inner-City Asthma Consortium
Investigators
Study Chair: Stanley Szefler, MD National Jewish Health
Study Chair: Stephen Teach, MD, MPH Children's Research Institute
  More Information

Additional Information:
Publications:
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
Results First Received: August 14, 2015
Last Updated: January 22, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
persistent allergic asthma
asthma exacerbations reduction
Xolair® (omalizumab)
Flovent® Diskus® (fluticasone)
placebo
inhaled corticosteroid therapy
anti-immunoglobulin E therapy
anti-IgE therapy

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

ClinicalTrials.gov processed this record on July 25, 2016