Allergic Sensitization, Asthma
Conditions
Keywords
asthma, allergen, allergic disease, allergen immunotherapy, allergic sensitization, atopic dermatitis, eczema, food allergy, oral mucosal immunoprophylaxis (OMIP)
Brief summary
The purpose of this study is to determine whether early childhood exposure to common allergens (substances that can trigger allergies and asthma) can prevent the development of asthma in children at high risk for developing the disease.
Detailed description
Researchers suspect that allergies to common inhaled allergens (such as house dust mite, cat dander, and grass pollens) are a major cause of childhood asthma. Recent evidence suggests that if allergies to inhaled allergens are prevented, this can cause changes in the immune system that may inhibit the development of asthma. Although strategies to prevent allergies generally focus on avoiding the allergen, complete avoidance of the common allergens linked to asthma would require extreme measures and is impractical. Oral mucosal immunoprophylaxis (OMIP) therapy is an allergy treatment that can induce long-lasting immune tolerance in people already suffering from allergies. By exposing the patient to small, repeated, but increasing doses of the problem allergen over a long period of time, the patient's immune system is eventually desensitized to that particular allergen. OMIP therapy has been shown to be safe in children as young as 2 years old. This study will evaluate if OMIP therapy against common inhaled allergens is safe and effective in preventing the development of asthma in children at high risk for developing the disease. Children enrolled in this study have been diagnosed with eczema or food allergies and have a family history of eczema, allergic rhinitis, or asthma. There are two groups in this study. The experimental arm participants will receive OMIP therapy (a mixture of house dust mite, cat, and timothy grass allergens) as daily oral drops under the tongue for 1 year; Placebo arm participants will receive an allergen free placebo solution. Participants will be followed for an additional 3 years to see whether they develop allergies or asthma and to determine how OMIP affects their immune system's response to allergens. There will be 5 study visits in the first year and 6 visits over the next 3 years. At all visits, participants will be assessed for allergy/asthma symptoms, will be asked to complete questionnaires, and may be asked to provide blood or saliva samples.
Interventions
BIOLOGICALOral mucosal immunoprophylaxis (OMIP)
OMIP consists of a mixture of allergen extracts including 0.2 milliliters (mL) timothy grass, 0.2 mL cat, and 0.2 mL house dust mite for a total daily dose of 0.6 mL.
BIOLOGICALPlacebo
The placebo consists of three 0.2 mL vials of solution mixed together for a total daily dose of 0.6 mL.
Sponsors
Immune Tolerance Network (ITN)
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Months to 30 Months
Healthy volunteers
No
Inclusion criteria
* Diagnosed with eczema (atopic dermatitis) * Family history of eczema, allergic rhinitis, or asthma * Allergy to one or more of the following: egg white, cow's milk, peanut, or soybean * Weigh at least 9.5 kg (20.9 lbs) * Parent or guardian willing to provide informed consent
Exclusion criteria
* Allergy to house dust mite, cat, or timothy grass * Born prematurely (before 36th week's gestation) * Previous diagnosis of asthma OR have had 3 or more distinct episodes of wheeze during the first year of life * Chronic pulmonary disease * Chronic disease requiring therapy * Past or current treatment with systemic immunomodulator medication * Past or current treatment with allergen-specific immunotherapy * Received 10 or more days of systemic steroids in the 3 months prior to study entry * Orofacial abnormalities that are likely to interfere with the subject's ability to take study treatment * Participated in another clinical study within the 3 months prior to study entry
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Allergic Sensitization at Month 36 Status Post Treatment Completion | Three years (36 months) after Treatment Completion | Allergic sensitization is defined as a positive serum allergen specific Immunoglobulin E (IgE) CAP test\[1\] or a positive allergy skin prick test\[2\]. Not experiencing allergic sensitization is the better outcome for this measure. 1. A positive serum allergen specific IgE CAP (ImmunoCAP) test result is defined by a result \>= 0.35 kU/L. Higher scores indicate greater allergic sensitization. 2. A positive skin prick test is defined as a wheal diameter that is 3 mm larger than that produced by a negative control. Higher wheal sizes indicate greater allergic reaction or sensitization. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Current Asthma at Month 36 Status Post Treatment Completion | Three years (36 months) after Treatment Completion | Participants who currently have asthma three years after end of treatment. Asthma is defined as three distinct episodes of wheeze after the first year of life, each of which lasts 3 or more consecutive days and occurs in a clinical setting where asthma is likely and other likely conditions have been excluded. Episodes must be separated by at least 7 days without wheeze. Current asthma is defined as a diagnosis of asthma and at least one episode of wheeze lasting 3 or more consecutive days in the past 12 months. |
| Time to First Onset of Asthma | From Treatment Initiation to Month 36 Status Post Treatment Completion | Time to first onset of asthma is the time from the day a participant is randomized and initiates study treatment to the diagnosis of the first of three episodes of asthma. Asthma is defined as three distinct episodes of wheeze after the first year of life, each of which lasts 3 or more consecutive days and occurs in a clinical setting where asthma is likely and other likely conditions have been excluded. Episodes must be separated by at least 7 days without wheeze. |
Countries
Australia, United States
Participant flow
Recruitment details
Subject recruitment occurred between June 2006 and July 2007 at 2 sites in Australia and 1 site in the United States
Pre-assignment details
At a screening visit, subjects underwent procedures to establish that all inclusion criteria were met and none of the exclusion criteria were met. All guardians provided written informed consent
Participants by arm
| Arm | Count |
|---|---|
| OMIP With Timothy Grass, Cat and House Dust Mite Allergens Participants were administered oral mucosal immunoprophylaxis (OMIP) daily for 12 months. OMIP consisted of a mixture of allergen extracts including 0.2 milliliters (mL) timothy grass, 0.2 mL cat, and 0.2 mL house dust mite for a total daily dose of 0.6 mL. After 12 months, treatment stopped and participants were tested 3 years after end of treatment for development of allergic sensitization and asthma. | 25 |
| Placebo Participants were administered via the same route as the experimental group an oral placebo solution daily for 12 months. The placebo consisted of three 0.2 mL vials of solution mixed together for a total daily dose of 0.6 mL. After 12 months, treatment stopped and participants were tested 3 years after end of treatment for development of allergic sensitization and asthma. | 26 |
| Total | 51 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 3 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | OMIP With Timothy Grass, Cat and House Dust Mite Allergens | Placebo | Total |
|---|---|---|---|
| Age, Customized Aged 12-17 Months | 6 participants | 6 participants | 12 participants |
| Age, Customized Aged 18-23 Months | 16 participants | 12 participants | 28 participants |
| Age, Customized Aged 24-30 Months | 3 participants | 8 participants | 11 participants |
| Region of Enrollment Australia | 21 participants | 22 participants | 43 participants |
| Region of Enrollment United States | 4 participants | 4 participants | 8 participants |
| Severity of Atopic Dermatitis (AD) Using SCORAD Index | 13.3 Units on a Scale STANDARD_DEVIATION 8.5 | 11.4 Units on a Scale STANDARD_DEVIATION 9.1 | 12.3 Units on a Scale STANDARD_DEVIATION 8.8 |
| Sex: Female, Male Female | 13 Participants | 12 Participants | 25 Participants |
| Sex: Female, Male Male | 12 Participants | 14 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 25 / 25 | 26 / 26 |
| serious Total, serious adverse events | 8 / 25 | 7 / 26 |
Outcome results
Primary
Number of Participants With Allergic Sensitization at Month 36 Status Post Treatment Completion
Allergic sensitization is defined as a positive serum allergen specific Immunoglobulin E (IgE) CAP test\[1\] or a positive allergy skin prick test\[2\]. Not experiencing allergic sensitization is the better outcome for this measure. 1. A positive serum allergen specific IgE CAP (ImmunoCAP) test result is defined by a result \>= 0.35 kU/L. Higher scores indicate greater allergic sensitization. 2. A positive skin prick test is defined as a wheal diameter that is 3 mm larger than that produced by a negative control. Higher wheal sizes indicate greater allergic reaction or sensitization.
Time frame: Three years (36 months) after Treatment Completion
Population: Intent-to-treat minus one participant in placebo group who had a sibling in trial
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OMIP With Timothy Grass, Cat and House Dust Mite Allergens | Number of Participants With Allergic Sensitization at Month 36 Status Post Treatment Completion | 22 participants |
| Placebo | Number of Participants With Allergic Sensitization at Month 36 Status Post Treatment Completion | 19 participants |
Comparison: Participants who drop out (have missing efficacy endpoints) are considered treatment failures.p-value: 0.2895% CI: [0.5, 10.5]Chi-squared
Secondary
Number of Participants With Current Asthma at Month 36 Status Post Treatment Completion
Participants who currently have asthma three years after end of treatment. Asthma is defined as three distinct episodes of wheeze after the first year of life, each of which lasts 3 or more consecutive days and occurs in a clinical setting where asthma is likely and other likely conditions have been excluded. Episodes must be separated by at least 7 days without wheeze. Current asthma is defined as a diagnosis of asthma and at least one episode of wheeze lasting 3 or more consecutive days in the past 12 months.
Time frame: Three years (36 months) after Treatment Completion
Population: Intent-to-treat minus one participant in placebo group who had a sibling in trial
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OMIP With Timothy Grass, Cat and House Dust Mite Allergens | Number of Participants With Current Asthma at Month 36 Status Post Treatment Completion | 4 participants |
| Placebo | Number of Participants With Current Asthma at Month 36 Status Post Treatment Completion | 4 participants |
Comparison: Participants who drop out (have missing efficacy endpoints) are considered treatment failures.p-value: 0.8595% CI: [0.2, 6.1]Chi-squared
Secondary
Time to First Onset of Asthma
Time to first onset of asthma is the time from the day a participant is randomized and initiates study treatment to the diagnosis of the first of three episodes of asthma. Asthma is defined as three distinct episodes of wheeze after the first year of life, each of which lasts 3 or more consecutive days and occurs in a clinical setting where asthma is likely and other likely conditions have been excluded. Episodes must be separated by at least 7 days without wheeze.
Time frame: From Treatment Initiation to Month 36 Status Post Treatment Completion
Population: Intent-to-treat minus one participant in placebo group who had a sibling in trial
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OMIP With Timothy Grass, Cat and House Dust Mite Allergens | Time to First Onset of Asthma | 31.0 Months | Standard Error 1.9 |
| Placebo | Time to First Onset of Asthma | 38.3 Months | Standard Error 2.1 |
p-value: 0.2895% CI: [0.6, 5.6]Regression, Logistic