Inner-City Anti-IgE Therapy for Asthma

Study Overview
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Brief Summary
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The purpose of this study is to find out if adding omalizumab to standard asthma treatment results in a safer, more effective, and longer lasting asthma treatment strategy than standard treatment alone, in inner-city children with mild to severe asthma.

Detailed Description
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This study is testing a medication called omalizumab for the treatment of asthma. Immunoglobulin E (IgE) is produced when one is exposed to allergens and it can cause inflammation in the lungs. Omalizumab can reduce inflammation and asthma attacks by blocking IgE. Unlike other medications for asthma, omalizumab is not an inhaler medication or pill. Instead, omalizumab is dissolved in a liquid and given by injection. Studies indicate that people living in the inner-city areas are more likely to be exposed to indoor allergens that are difficult to avoid than people living in other areas. The purpose of this study is to find out if adding omalizumab to standard asthma treatment results in a safer, more effective, and longer lasting asthma treatment strategy than standard treatment alone. This study will recruit inner-city children and adolescents with moderate to severe allergic asthma. This study will last about 1.5 to 2 years. Participants will be randomly assigned to receive either omalizumab or placebo injections once every 2 or 4 weeks. The injection schedule will be determined based on the participant's weight and total IgE. Both groups will receive standardized specialist care and basic asthma education including environmental control measures. Participants must have some form of health care insurance to cover the costs of asthma controller medications prescribed during the study. Participants will complete a series of questionnaires about topics including perceived stress, home environment, physical activity, diet and nutrition, smoking habits, and quality of life. At study entry and monthly throughout the study, participants will complete questionnaires about their asthma symptoms and medical resource utilization. Some visits will include a physical examination, vital signs measurement, lung function tests, asthma medication evaluation, and an asthma action plan. Blood collection is required up to eight times during the study for safety labs.

Official Title
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Inner-City Anti-IgE Therapy for Asthma (ICAC-08)

Conditions
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Asthma

Intervention / Treatment
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* Biological: omalizumab
* Biological: omalizumab placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Both body weight and total serum IgE suitable for omalizumab dosing. Diagnosis of asthma made by a physician more than 1 year prior to study entry OR diagnosis of asthma made less than 1 year prior to study entry but have had asthma symptoms for longer than 1 year prior to study entry Are receiving long-term asthma control therapy OR have symptoms consistent with persistent asthma OR have evidence of uncontrolled disease Positive prick skin test to at least one perennial allergen (e.g., dust mite, cockroach, mold, cat, dog, rat, mouse) Live in a preselected zip code are Able to perform spirometry measurements Willing to sign informed consent or have parent or guardian willing to provide informed consent Previously had chicken pox or received varicella (chicken pox) vaccine Have some form of health care insurance that covers costs of medications Exclusion Criteria: If participant meets any of these criteria, they are not eligible at that time but may be reassessed: Systemic prednisone (or equivalent) during the 2 weeks prior to Visit 2 Systemic prednisone (or equivalent) for more than 30 of the 60 days prior to study entry Pregnancy or breastfeeding Acute sinusitis or chest infection requiring antibiotics within 1 month of study screening Currently participating in another asthma-related clinical trial or have previously participated in an another asthma-related trial within 1 month of study entry Does not sleep at least 4 nights per week in one home Lives with a foster parent Does not have access to a phone Plans to move during the study Previously treated with anti-IgE therapy within 1 year of study entry Currently receiving or received hyposensitization therapy to any allergen in the year prior to study entry Previously received hyposensitization therapy to dust mite, Alternaria, or cockroach for more than 6 months in the 3 years prior to study entry If participant meets any of these criteria, they are not eligible for the study and may not be reassessed: Significant medical illness. More information on this criterion can be found in the protocol. Certain medications within 4 weeks of study screening. More information on this criterion can be found in the protocol. Known hypersensitivity to any ingredients of omalizumab or related drugs Diagnosis of cancer, being investigated for possible cancer, or history of cancer Will not allow study physician to manage their asthma Does not primarily speak English (or Spanish at centers with Spanish-speaking staff) History of severe anaphylactoid or anaphylactic reaction(s)

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Omalizumab (Xolair) + Conventional Therapy<br>Omalizumab was administered subcutaneously every 2 or 4 weeks over a period of 60 weeks to participants classified as having moderate to severe asthma. Doses (mg) and dosing frequency were determined by serum total 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-II, 2002) guidelines, under the management of an asthma specialist health care provider. | Biological: omalizumab<br>* Subcutaneous injections of omalizumab will be administered every 2 or 4 weeks along with standard of care for asthma for 60 weeks, beginning with the Randomization Visit. Dosage is dependent on participant's individual characteristics.<br>* Other names: Anti-IgE antibody,humanized monoclonal;|
| Placebo Comparator: Placebo + Conventional Therapy<br>Placebo was administered subcutaneously every 2 or 4 weeks over a period of 60 weeks to participants classified as having moderate to severe asthma. Doses (mg) and dosing frequency were determined by serum total 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-II, 2002) guidelines, under the management of an asthma specialist health care provider. | Biological: omalizumab placebo<br>* Subcutaneous injections of placebo will be administered every 2 or 4 weeks along with standard of care for asthma for 60 weeks, beginning with the Randomization Visit. Dosage is dependent on participant's individual characteristics.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Number of Asthma Symptom Days | Maximum symptom days was calculated as the largest of the following variables: number of days with wheezing, chest tightness, or cough; number of nights of sleep disturbance; and number of days when activities were affected. This symptom scale ranges from 0 to 14 days per a 2-week look-back period. A higher score reflected a greater number of asthma symptoms. Data represent an average of those collected in the time period (weeks 12-60), where at least one value was available in this assessment period and at baseline for a participant. | Weeks 12-60: 12 months of assessments starting 12 weeks after the initiation of study treatment. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Economic Outcome: Comparison of Number of Missed School Days Due to Asthma | The number of school days missed was available for 307 of the 419 (73%) study participants, of which 152 were in the Omalizumab (Xolair) + Conventional Therapy arm. Source of data: caretaker/participant self-report. Data represent an average of those collected in the time period (weeks 12-60), where at least one value was available in this assessment period and at baseline for a participant. | Weeks 12-60: 12 months of assessments starting 12 weeks after the initiation of study treatment. | 
| Economic Outcome: Number of Missed Work Days by Caretaker Due to Asthma | The number of work days missed by the caretaker due to the study participant's asthma was available for 138 of 419 (33%) study participant caretakers. Source of data: caretaker self-report. Data represent an average of those collected in the time period (weeks 12-60). | Weeks 12-60: 12 months of assessments starting 12 weeks after the initiation of study treatment. | 
| Child Asthma Control Test (C-ACT) Score | 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. C-ACT scores were available as an outcome measure in 236 of the 419 participants, 118 of whom were in the Omalizumab (Xolair) + Conventional Therapy arm. Data represent an average of those collected in the time period (weeks 12-60), where at least one value was available in this assessment period and at baseline for a participant. | Weeks 12-60: 12 months of assessments starting 12 weeks after the initiation of treatment. | 
| Asthma Control Test (ACT) Score | The Asthma Control Test (ACT) is a validated tool to assess overall asthma control (over the last 4 weeks) in patients >= 12 years of age. It is a questionnaire comprised of 5 questions assessing: asthma symptoms, use of rescue medications, and the impact of asthma on everyday functioning. All questions are scored on a 5-point Likert scale, with a higher score indicating better control. All scores were added together to calculate a total score. Total scores can range from 5 to 25. A score of 19 or less is indicative of asthma that is not well controlled. The minimally important difference for ACT is 3 points. ACT scores as an outcome measure were available in 150 of the 419 participants, 77 of whom were in the Omalizumab (Xolair) + Conventional Therapy arm. Data represent an average of those collected in the time period (weeks 12-60), where at least one value was available in this assessment period and at baseline for a participant. | Weeks 12-60: 12 months of assessments starting 12 weeks after the initiation of study treatment. | 
| Forced Expiratory Volume in 1 Second (FEV1) % Predicted | FEV1 is air volume exhaled in 1 second during spirometry. For the trial, mild asthma is defined as pre-bronchodilator FEV1 ≥80% predicted, requiring no/low-moderate dose of inhaled glucocorticoids; moderate asthma and severe asthma, respectively, as pre-bronchodilator FEV1 <80% predicted requiring the same glucocorticoids as mild asthma and FEV1 <80% predicted requiring high-dose inhaled glucocorticoids (with/without continuous oral glucocorticoids) or uncontrolled despite treatment. FEV1 % of predicted is FEV1 converted to a percentage of normal, based on height, weight, and race. FEV1 percent predicted data as an outcome measure were available in 363 of the 419 participants, 190 of whom were in the Omalizumab (Xolair) + Conventional Therapy arm. Data represent an average of those collected in the time period (weeks 12-60), where at least one value was available in this assessment period and at baseline for a participant. | Weeks 12-60: 12 months of assessments starting 12 weeks after the initiation of study treatment. | 
| FEV1/FVC Ratio | 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%. FEV1/FVC ratio data as an outcome measure were available in 363 of the 419 participants, 190 of whom were in the Omalizumab (Xolair) + Conventional Therapy arm. Data represent an average of those collected in the time period (weeks 12-60), where at least one value was available in this assessment period and at baseline for a participant. | Weeks 12-60: 12 months of assessments starting 12 weeks after the initiation of study treatment. | 
| Exhaled Nitric Oxide | Exhaled nitric oxide is a biomarker of airway inflammation. Measurement (in parts per billion,ppb) of exhaled nitric oxide (eNO) prior to spirometry, employing a technique modified after Silkoff et al (1997) and following American Thoracic Society guidelines for eNO assessment (American Thoracic Society, 1999). Nitric oxide concentrations were measured using a rapid-response chemiluminescent analyzer (NIOX™ System, Aerocrine, Sweden) which has a response time of < 700 ms for 10-90% full scale. The Food and Drug Administration has approved this device for clinical application in asthma management. Data represent an average of those collected in the time period (weeks 12-60), where at least one value was available in this assessment period and at baseline for a participant. | Weeks 12-60: 12 months of assessments starting 12 weeks after the initiation of study treatment. | 
| Percent Adherence to Asthma Medication | 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 every 3 months. Adherence data as an outcome were available in 384 of the 419 participants, 193 of whom were in the Omalizumab (Xolair) + Conventional Therapy arm. Data represent an average of those collected in the time period (weeks 12-60), where at least one value was available in this assessment period and at baseline for a participant. | Weeks 12-60: 12 months of assessments starting 12 weeks after the initiation of study treatment | 
| Percent Prevalence: Treatment Step Level 1 or 2 (Mild Asthma) | Treatment steps were established, per the National Asthma Education and Prevention Program Expert Panel Report 3 guidelines. Steps 1-2 apply to mild asthma, 3 to moderate asthma, and 4-6 to severe asthma. At Step 0, the recommendation is for no asthma-control medication or albuterol as needed; at 1, budesonide 180 mcg once a day; at 2, budesonide 180 mcg twice a day; at 3, budesonide 360 mcg twice a day; at 4, fluticasone-salmeterol (Advair, GlaxoSmithKline) 250 mcg fluticasone and 50 mcg salmeterol twice a day; at 5, Advair 250 mcg and 50 mcg twice a day plus montelukast once a day; and at 6, Advair 500 mcg and 50 mcg twice a day plus montelukast once a day. (The doses for montelukast are 5 mg per day for those <=14 years old and 10 mg per day for those >=15 years.) Data represent an average of those in the time period, where at >/= 1 value was available in this period and at baseline for a participant; results are model predicted numbers (e.g.,odds ratios converted to percentages). | Weeks 12-60: 12 months of assessments starting 12 weeks after the initiation of study treatment | 
| Percent Prevalence: Treatment Step Level 4 Through 6 (Severe Asthma) | Steps were established, per the National Asthma Education and Prevention Program Expert Panel Report 3 guidelines. Steps 1-2 apply to mild asthma, 3 to moderate asthma, and 4-6 to severe asthma. At Step 0, the recommendation is for no asthma-control medication or albuterol as needed; at 1, budesonide 180 mcg once a day; at 2, budesonide 180 mcg twice a day; at 3, budesonide 360 mcg twice a day; at 4, fluticasone-salmeterol (Advair, GlaxoSmithKline) 250 mcg fluticasone and 50 mcg salmeterol twice a day; at 5, Advair 250 mcg and 50 mcg twice a day plus montelukast once a day; and at 6, Advair 500 mcg and 50 mcg twice a day plus montelukast once a day. (The doses for montelukast are 5 mg per day for those <=14 years old and 10 mg per day for those >=15 years.) Data represent an average of those in the time period, where at least one value was available in this period and at baseline for a participant. Results values are model predicted numbers,(e.g, odds ratios converted to percentages). | Weeks 12-60: 12 months of assessments starting 12 weeks after the initiation of study treatment | 
| Dose Inhaled Corticosteroids (Glucocorticoids) | Prescribed dose (mcg/day) of inhaled glucocorticoids to maintain asthma control. The dose of inhaled glucocorticoids was converted to the budesonide-equivalent dose. Data represent an average of those collected in the time period (weeks 12-60), where at least one value was available in this assessment period and at baseline for a participant. | Weeks 12-60: 12 months of assessments starting 12 weeks after the initiation of study treatment. | 
| Percent Prevalence: Prescribed Rescue Beta 2 Agonists | Percent of participants prescribed long-acting beta 2 agonists to maintain asthma control. Data represent an average of those collected in the time period (weeks 12-60), where at least one value was available in this assessment period and at baseline for a participant. Results values are model predicted numbers, (e.g.,odds ratios converted to percentages). | Weeks 12-60: 12 months of assessments starting 12 weeks after the initiation of study treatment. | 
| Percent Prevalence: Asthma-Related Medical Care Resource Utilization - Hospitalizations | Percent participants with >=1 hospitalizations. A hospitalization is defined as an asthma-related, overnight hospitalization. . Results values are model predicted numbers,(e.g., odds ratios converted to percentages). | Weeks 12-60: 12 months of assessments starting 12 weeks after the initiation of study treatment. | 
| Percent Prevalence: Asthma Exacerbations | Percent participants with >=1 exacerbations. An exacerbation was defined as a prednisone burst (a minimum of 20 mg per day of prednisone, or the equivalent, taken for any 3 of 5 consecutive days) or hospitalization. Results values are model predicted numbers, (e.g.,odds ratios converted to percentages). | Weeks 12-60: 12 months of assessments starting 12 weeks after the initiation of study treatment. | 
| Asthma Caregiver's Quality of Life Questionnaire (PACQLQ) Overall Score | Asthma-Specific Quality of Life (QOL) Measure . The PACQLQ is a validated tool that measures limitations and anxieties faced by primary caregivers of children with asthma. Scores are calculated as the mean score within two domains of questions (re: activity limitation and emotional function) and overall scores represent the mean across all questions. The use of the PACQLQ is valid for use in the caretakers of children ages 7 to 17 years of age. Higher scores indicate better quality of life. Minimum possible score is 1 (maximum impairment); maximum possible score is 7 (no impairment). The range of actual scores were a minimum of 2.4 and a maximum of 7. Method: Caretaker self-report. PACQLQ scores were available for 320 of 419 (76%) of study participant caretakers (159 in the Omalizumab (Xolair) + Conventional Therapy arm). | Week 60 | 
| Paediatric Asthma Quality of Life Questionnaire (PAQLQ) Overall Score | Asthma-specific quality of life (QOL) validated tool designed for children 7 to 17 years of age. PAQLQ measures functional problems that are most troublesome to children with asthma. PAQLQ has 23 questions in 3 domains (activity limitation=5, emotional function=8, symptoms=10). Patients responded to each question on a 7-point Likert scale. Overall PAQLQ score is mean of 23 questions; each domain score is mean of questions in that domain. Minimum possible score is 1 (maximum impairment); maximum possible score is 7 (no impairment). Actual scores ranged from 2.1 to 7. PAQLQ scores were available for 338 of 419 (81%) of study participants, 170 of whom were in the Omalizumab (Xolair) + Conventional Therapy arm. | Week 60 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immunoglobulins, Immunoglobulin E, omalizumab, anti-IgE