Trial Outcomes & Findings for Allergy Immunotherapy for the Reduction of Asthma (NCT NCT01028560)

NCT ID: NCT01028560

Last Updated: 2019-05-28

Results Overview

The Asthma Severity Score is a customized score created for this study due to the lack of standardized instruments for this age group. It takes into account asthma symptom severity and frequency, as well as asthma medication dosing and potency. Data was collected at baseline and every 2 weeks through interviews conducted over the phone. If the caregiver could not be reached by the phone, the interview was conducted at the next face-to face opportunity (study or injection visit). The minimum score on this scale is 0 (no asthma symptoms and no asthma medicines used during the 14 day interview period). The maximum score is 224 (uncontrolled severe asthma with severe cough, shortness of breath and wheezing on 14 of 14 days, using Albuterol 2 puffs 4x/day, budesonide/formoterol 160ug/4.5ug 2 puffs twice daily and Montelukast 4mg daily on 14 of 14 days). Scores calculated from the collected data were averaged to produce one reported value at baseline and year 1, 2 and 3.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

58 participants

Primary outcome timeframe

baseline and every two weeks up to end of study (up to 36 months)

Results posted on

2019-05-28

Participant Flow

58 children were recruited from one tertiary treatment center, Jacobi Medical Center, which is the largest city hospital in the Bronx, New York. The referral population consists of primarily low-income, Medicaid beneficiaries residing in the Bronx.

There was no run-in phase. After consents were signed (by the parents), the 58 participants were immediately randomized into treatment or control group. 8 of the 58 participants were withdrawn from the study immediately after randomization, so only 50 participants began protocol treatment.

Participant milestones

Participant milestones
Measure
No Immunotherapy, Receive Standard of Care Asthma Treatment
This group consists of children who do not receive allergy immunotherapy. No placebo injections were used. The control group received standard of care asthma and allergy treatment, excluding allergy immunotherapy (subcutaneous or other routes). Standard of care: standard of care asthma and allergy treatment (medications, advice to environmental remediation)
Allergen Immunotherapy
This group receives initially weekly, later biweekly subcutaneous injections of a mixture of allergen extracts, tailored to the individual child's allergy sensitization profile. The maximum number of injections at each visit is 1-3 injections per child. In addition to allergy immunotherapy, this group receives standard of care asthma and allergy treatment (medications, advice to environmental remediation) Allergy immunotherapy consists of regular subcutaneous injections of an individualized mixture of allergen extracts according to the allergy sensitization profile of each child. Increasing doses of allergen extract are given in 1-3 injections until a predetermined maintenance dose is reached. This maintenance dose varies by extract and accords to the general practice guidelines of immunotherapy. To increase safety, the cumulative monthly maintenance doses are divided into biweekly visits during the maintenance phase. Standard of care: standard of care asthma and allergy treat
Overall Study
STARTED
27
31
Overall Study
Started Study Protocol
23
27
Overall Study
COMPLETED
17
13
Overall Study
NOT COMPLETED
10
18

Reasons for withdrawal

Reasons for withdrawal
Measure
No Immunotherapy, Receive Standard of Care Asthma Treatment
This group consists of children who do not receive allergy immunotherapy. No placebo injections were used. The control group received standard of care asthma and allergy treatment, excluding allergy immunotherapy (subcutaneous or other routes). Standard of care: standard of care asthma and allergy treatment (medications, advice to environmental remediation)
Allergen Immunotherapy
This group receives initially weekly, later biweekly subcutaneous injections of a mixture of allergen extracts, tailored to the individual child's allergy sensitization profile. The maximum number of injections at each visit is 1-3 injections per child. In addition to allergy immunotherapy, this group receives standard of care asthma and allergy treatment (medications, advice to environmental remediation) Allergy immunotherapy consists of regular subcutaneous injections of an individualized mixture of allergen extracts according to the allergy sensitization profile of each child. Increasing doses of allergen extract are given in 1-3 injections until a predetermined maintenance dose is reached. This maintenance dose varies by extract and accords to the general practice guidelines of immunotherapy. To increase safety, the cumulative monthly maintenance doses are divided into biweekly visits during the maintenance phase. Standard of care: standard of care asthma and allergy treat
Overall Study
Lack of Efficacy
3
6
Overall Study
Withdrawal by Subject
7
12

Baseline Characteristics

Allergy Immunotherapy for the Reduction of Asthma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
No Immunotherapy, Receive Standard of Care Asthma Treatment
n=23 Participants
This group only receives standard of care asthma and allergy treatment. This does not receive allergy immunotherapy. Both the experimental group and the control group receive otherwise standard of care asthma and allergy treatment.
Allergen Immunotherapy
n=27 Participants
This group receives initially weekly, later biweekly subcutaneous injections of a mixture of allergen extracts, tailored to the individual child's allergy sensitization profile. The maximum number of injections at each visit is 1-3 injections per child. In addition to allergy immunotherapy. this group receives standard of care asthma and allergy treatment Allergen extracts (subcutaneous injections): Allergy immunotherapy consists of regular subcutaneous injections of an individualized mixture of allergen extracts according to the allergy sensitization profile of each child. Increasing doses of allergen extract are given in 1-3 injections until a predetermined maintenance dose is reached. For safety, the cumulative monthly maintenance doses are divided into biweekly visits during the maintenance phase. Both the experimental group and the control group receive otherwise standard of care asthma and allergy treatment.
Total
n=50 Participants
Total of all reporting groups
Age, Continuous
3.1 years
STANDARD_DEVIATION 0.8 • n=5 Participants
3.0 years
STANDARD_DEVIATION 0.8 • n=7 Participants
3.1 years
STANDARD_DEVIATION 0.8 • n=5 Participants
Sex: Female, Male
Female
5 Participants
n=5 Participants
3 Participants
n=7 Participants
8 Participants
n=5 Participants
Sex: Female, Male
Male
18 Participants
n=5 Participants
24 Participants
n=7 Participants
42 Participants
n=5 Participants
Race/Ethnicity, Customized
Ethnicity · Hispanic/Latino
15 Participants
n=5 Participants
20 Participants
n=7 Participants
35 Participants
n=5 Participants
Race/Ethnicity, Customized
Ethnicity · Black/African American
5 Participants
n=5 Participants
7 Participants
n=7 Participants
12 Participants
n=5 Participants
Race/Ethnicity, Customized
Ethnicity · Unknown/not reported
3 Participants
n=5 Participants
0 Participants
n=7 Participants
3 Participants
n=5 Participants
Number of children with asthma related Emergency Department visits prior to enrollment
21 Participants
n=5 Participants
25 Participants
n=7 Participants
46 Participants
n=5 Participants

PRIMARY outcome

Timeframe: baseline and every two weeks up to end of study (up to 36 months)

Population: All participants were included in this analysis that started immunotherapy, regardless if they completed it or not (intention to treat analysis)

The Asthma Severity Score is a customized score created for this study due to the lack of standardized instruments for this age group. It takes into account asthma symptom severity and frequency, as well as asthma medication dosing and potency. Data was collected at baseline and every 2 weeks through interviews conducted over the phone. If the caregiver could not be reached by the phone, the interview was conducted at the next face-to face opportunity (study or injection visit). The minimum score on this scale is 0 (no asthma symptoms and no asthma medicines used during the 14 day interview period). The maximum score is 224 (uncontrolled severe asthma with severe cough, shortness of breath and wheezing on 14 of 14 days, using Albuterol 2 puffs 4x/day, budesonide/formoterol 160ug/4.5ug 2 puffs twice daily and Montelukast 4mg daily on 14 of 14 days). Scores calculated from the collected data were averaged to produce one reported value at baseline and year 1, 2 and 3.

Outcome measures

Outcome measures
Measure
No Immunotherapy, Receive Standard of Care Asthma Treatment
n=23 Participants
This group only receives standard of care asthma and allergy treatment. This does not receive allergy immunotherapy. Both the experimental group and the control group receive otherwise standard of care asthma and allergy treatment.
Allergen Immunotherapy
n=27 Participants
This group receives initially weekly, later biweekly subcutaneous injections of a mixture of allergen extracts, tailored to the individual child's allergy sensitization profile. The maximum number of injections at each visit is 1-3 injections per child. In addition to allergy immunotherapy. this group receives standard of care asthma and allergy treatment Allergen extracts (subcutaneous injections): Allergy immunotherapy consists of regular subcutaneous injections of an individualized mixture of allergen extracts according to the allergy sensitization profile of each child. Increasing doses of allergen extract are given in 1-3 injections until a predetermined maintenance dose is reached. For safety, the cumulative monthly maintenance doses are divided into biweekly visits during the maintenance phase. Both the experimental group and the control group receive otherwise standard of care asthma and allergy treatment.
Asthma Severity as Measured by the Asthma Severity Score (Averaged up to 36 Months)
Score at baseline
21.95 score on a scale
Standard Error 3.74
25.68 score on a scale
Standard Error 3.53
Asthma Severity as Measured by the Asthma Severity Score (Averaged up to 36 Months)
Score at Year 1
27.72 score on a scale
Standard Error 3.52
27.85 score on a scale
Standard Error 3.34
Asthma Severity as Measured by the Asthma Severity Score (Averaged up to 36 Months)
Score at Year 2
31.40 score on a scale
Standard Error 4.16
29.68 score on a scale
Standard Error 4.03
Asthma Severity as Measured by the Asthma Severity Score (Averaged up to 36 Months)
Score at Year 3
33.00 score on a scale
Standard Error 5.23
31.15 score on a scale
Standard Error 5.11

SECONDARY outcome

Timeframe: Baseline and end of treatment (36 months)

Population: In the intention to treat analysis, only 30 children (15 in each group) had serum tests available at baseline and after 36 months of the study.

Young children with allergies tend to develop additional environmental allergies over time. This study investigated if allergy immunotherapy could be used to prevent the development of new allergic sensitizations. Participants were tested for sensitivity to a panel of 8 common environmental allergens. Testing was conducted via serum specific immunoglobulin E (IgE) testing. A test was considered negative (non-allergic) if the specific IgE level was \<0.35 kIU/L (Kilo International Units/Liter) and positive (allergic) if the levels was \>0.35 kIU/L. A "test pair" is the result of a serum IgE test, for a specific allergen, done at two different times. Test pairs can be negative-negative, negative-positive (newly gained allergic sensitization), positive-negative (lost sensitization) or positive-positive. Reported values indicate the total number of newly gained allergic sensitization (negative-positive) for the group.

Outcome measures

Outcome measures
Measure
No Immunotherapy, Receive Standard of Care Asthma Treatment
n=103 test pairs (baseline and at 36+/-6months
This group only receives standard of care asthma and allergy treatment. This does not receive allergy immunotherapy. Both the experimental group and the control group receive otherwise standard of care asthma and allergy treatment.
Allergen Immunotherapy
n=105 test pairs (baseline and at 36+/-6months
This group receives initially weekly, later biweekly subcutaneous injections of a mixture of allergen extracts, tailored to the individual child's allergy sensitization profile. The maximum number of injections at each visit is 1-3 injections per child. In addition to allergy immunotherapy. this group receives standard of care asthma and allergy treatment Allergen extracts (subcutaneous injections): Allergy immunotherapy consists of regular subcutaneous injections of an individualized mixture of allergen extracts according to the allergy sensitization profile of each child. Increasing doses of allergen extract are given in 1-3 injections until a predetermined maintenance dose is reached. For safety, the cumulative monthly maintenance doses are divided into biweekly visits during the maintenance phase. Both the experimental group and the control group receive otherwise standard of care asthma and allergy treatment.
Number of Newly Gained Allergic Sensitizations as Assessed by Serum Specific Immunoglobulin E (IgE) Testing
12 Newly gained allergic sensitizations
16 Newly gained allergic sensitizations

SECONDARY outcome

Timeframe: Baseline and every 12 months until end of treatment (36 months)

Population: Only 27 participants had yearly data for Treg cells from baseline through 36 months (+/- 6 months). Data for 23 participants were not included in the analysis because either parents declined to have blood drawn or because results were not returned from the outside laboratory (despite many efforts to retrieve these data).

T regulatory cells are thought to play a role in mediating the effects of immunotherapy in increasing allergen tolerance and dampen the clinical expression of allergy. However, existing studies have not found clear relationship between numbers of T regulatory cells in blood and effect of immunotherapy. The aim of this analysis was to observe potential changes in T regulatory cell numbers in response to immunotherapy in this age group. Peripheral blood cells were acquired and analyzed for T regulatory (Treg) cell markers. In molecular biology, CD4+ (cluster of differentiation 4), a particular cell marker, is a glycoprotein found on the surface of immune cells such as T helper cells and certain groups of T regulatory cells. Testing was done at baseline and then every 12 months. Reported values represents the percentage of CD4+ that are Treg cells.

Outcome measures

Outcome measures
Measure
No Immunotherapy, Receive Standard of Care Asthma Treatment
n=13 Participants
This group only receives standard of care asthma and allergy treatment. This does not receive allergy immunotherapy. Both the experimental group and the control group receive otherwise standard of care asthma and allergy treatment.
Allergen Immunotherapy
n=14 Participants
This group receives initially weekly, later biweekly subcutaneous injections of a mixture of allergen extracts, tailored to the individual child's allergy sensitization profile. The maximum number of injections at each visit is 1-3 injections per child. In addition to allergy immunotherapy. this group receives standard of care asthma and allergy treatment Allergen extracts (subcutaneous injections): Allergy immunotherapy consists of regular subcutaneous injections of an individualized mixture of allergen extracts according to the allergy sensitization profile of each child. Increasing doses of allergen extract are given in 1-3 injections until a predetermined maintenance dose is reached. For safety, the cumulative monthly maintenance doses are divided into biweekly visits during the maintenance phase. Both the experimental group and the control group receive otherwise standard of care asthma and allergy treatment.
Peripheral Blood T Regulatory Cells as a Percentage of CD4+ (Cluster of Differentiation 4) Cells
Baseline average Treg %
4.87 % of CD4+ cells are Treg cells
Standard Error 0.65
5.90 % of CD4+ cells are Treg cells
Standard Error 0.62
Peripheral Blood T Regulatory Cells as a Percentage of CD4+ (Cluster of Differentiation 4) Cells
1st Year Treg percentage
5.09 % of CD4+ cells are Treg cells
Standard Error 0.66
5.30 % of CD4+ cells are Treg cells
Standard Error 0.73
Peripheral Blood T Regulatory Cells as a Percentage of CD4+ (Cluster of Differentiation 4) Cells
2nd Year Treg percentage
5.26 % of CD4+ cells are Treg cells
Standard Error 0.72
5.76 % of CD4+ cells are Treg cells
Standard Error 0.74
Peripheral Blood T Regulatory Cells as a Percentage of CD4+ (Cluster of Differentiation 4) Cells
3rd Year Treg percentage
5.499 % of CD4+ cells are Treg cells
Standard Error 0.92
7.08 % of CD4+ cells are Treg cells
Standard Error 0.77

SECONDARY outcome

Timeframe: From baseline through end of study (maximum 36 months)

Population: Participants with available data (intention to treat population)

Any reported use of consequent systemic corticosteroid use due to asthma exacerbation counted as one "corticosteroid burst" (CSB). For example, if a child used 5 days of prednisolone due to asthma exacerbation, this counted as one corticosteroid burst (CSB). An interval of at least 7 days was determined to be necessary to count 2 courses of systemic corticosteroids as separated bursts. The presented data reflect the intention-to-treat analysis. The time between baseline and each participant's study end time was counted towards the "years in study". The incidence rate describes the number of CSB per child per "year in study".

Outcome measures

Outcome measures
Measure
No Immunotherapy, Receive Standard of Care Asthma Treatment
n=23 Participants
This group only receives standard of care asthma and allergy treatment. This does not receive allergy immunotherapy. Both the experimental group and the control group receive otherwise standard of care asthma and allergy treatment.
Allergen Immunotherapy
n=27 Participants
This group receives initially weekly, later biweekly subcutaneous injections of a mixture of allergen extracts, tailored to the individual child's allergy sensitization profile. The maximum number of injections at each visit is 1-3 injections per child. In addition to allergy immunotherapy. this group receives standard of care asthma and allergy treatment Allergen extracts (subcutaneous injections): Allergy immunotherapy consists of regular subcutaneous injections of an individualized mixture of allergen extracts according to the allergy sensitization profile of each child. Increasing doses of allergen extract are given in 1-3 injections until a predetermined maintenance dose is reached. For safety, the cumulative monthly maintenance doses are divided into biweekly visits during the maintenance phase. Both the experimental group and the control group receive otherwise standard of care asthma and allergy treatment.
Incidence Rate of Systemic Corticosteroid Bursts (CSB) Per Child
1.28 Number of CSB per child per year
Interval 1.03 to 1.6
1.55 Number of CSB per child per year
Interval 1.26 to 1.9

Adverse Events

No Immunotherapy, Receive Standard of Care Asthma Treatment

Serious events: 7 serious events
Other events: 0 other events
Deaths: 0 deaths

Allergen Immunotherapy

Serious events: 6 serious events
Other events: 22 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
No Immunotherapy, Receive Standard of Care Asthma Treatment
n=23 participants at risk
This group consists of children who do not receive allergy immunotherapy. Both groups - the experimental as well as the control group receive otherwise standard of care asthma and allergy treatment Standard of care: standard of care asthma and allergy treatment
Allergen Immunotherapy
n=27 participants at risk
This group receives initially weekly, later biweekly subcutaneous injections of a mixture of allergen extracts, tailored to the individual child's allergy sensitization profile. The maximum number of injections at each visit is 1-3 injections per child. In addition to allergy immunotherapy. this group receives standard of care asthma and allergy treatment Allergen extracts (subcutaneous injections): Allergy immunotherapy consists of regular subcutaneous injections of an individualized mixture of allergen extracts according to the allergy sensitization profile of each child. Increasing doses of allergen extract are given in 1-3 injections until a predetermined maintenance dose is reached. This maintenance dose varies by extract and accords to the general practice guidelines of immunotherapy. To increase safety the cumulative monthly maintenance doses are divided into biweekly visits during the maintenance phase. Standard of care: standard of care asthma and allergy treat
Respiratory, thoracic and mediastinal disorders
Asthma related hospitalization
30.4%
7/23 • Number of events 14 • Adverse event data was collected during the 3-year study period.
Definition: Serious adverse events= hospitalization, death In the immunotherapy group, all allergic or asthmatic events occurring the 48 hours after immunotherapy injections had been administered were considered a possible consequence of immunotherapy (immediate or late allergic reaction). Immediate type reactions were defined as any allergic reaction occurring within 2 hours after the injections.
22.2%
6/27 • Number of events 11 • Adverse event data was collected during the 3-year study period.
Definition: Serious adverse events= hospitalization, death In the immunotherapy group, all allergic or asthmatic events occurring the 48 hours after immunotherapy injections had been administered were considered a possible consequence of immunotherapy (immediate or late allergic reaction). Immediate type reactions were defined as any allergic reaction occurring within 2 hours after the injections.
Skin and subcutaneous tissue disorders
Cellulitis/skin abscess/infected insect bite
17.4%
4/23 • Number of events 4 • Adverse event data was collected during the 3-year study period.
Definition: Serious adverse events= hospitalization, death In the immunotherapy group, all allergic or asthmatic events occurring the 48 hours after immunotherapy injections had been administered were considered a possible consequence of immunotherapy (immediate or late allergic reaction). Immediate type reactions were defined as any allergic reaction occurring within 2 hours after the injections.
3.7%
1/27 • Number of events 1 • Adverse event data was collected during the 3-year study period.
Definition: Serious adverse events= hospitalization, death In the immunotherapy group, all allergic or asthmatic events occurring the 48 hours after immunotherapy injections had been administered were considered a possible consequence of immunotherapy (immediate or late allergic reaction). Immediate type reactions were defined as any allergic reaction occurring within 2 hours after the injections.
Infections and infestations
pneumonia
0.00%
0/23 • Adverse event data was collected during the 3-year study period.
Definition: Serious adverse events= hospitalization, death In the immunotherapy group, all allergic or asthmatic events occurring the 48 hours after immunotherapy injections had been administered were considered a possible consequence of immunotherapy (immediate or late allergic reaction). Immediate type reactions were defined as any allergic reaction occurring within 2 hours after the injections.
3.7%
1/27 • Number of events 1 • Adverse event data was collected during the 3-year study period.
Definition: Serious adverse events= hospitalization, death In the immunotherapy group, all allergic or asthmatic events occurring the 48 hours after immunotherapy injections had been administered were considered a possible consequence of immunotherapy (immediate or late allergic reaction). Immediate type reactions were defined as any allergic reaction occurring within 2 hours after the injections.
Infections and infestations
tooth abscess
4.3%
1/23 • Number of events 1 • Adverse event data was collected during the 3-year study period.
Definition: Serious adverse events= hospitalization, death In the immunotherapy group, all allergic or asthmatic events occurring the 48 hours after immunotherapy injections had been administered were considered a possible consequence of immunotherapy (immediate or late allergic reaction). Immediate type reactions were defined as any allergic reaction occurring within 2 hours after the injections.
0.00%
0/27 • Adverse event data was collected during the 3-year study period.
Definition: Serious adverse events= hospitalization, death In the immunotherapy group, all allergic or asthmatic events occurring the 48 hours after immunotherapy injections had been administered were considered a possible consequence of immunotherapy (immediate or late allergic reaction). Immediate type reactions were defined as any allergic reaction occurring within 2 hours after the injections.

Other adverse events

Other adverse events
Measure
No Immunotherapy, Receive Standard of Care Asthma Treatment
n=23 participants at risk
This group consists of children who do not receive allergy immunotherapy. Both groups - the experimental as well as the control group receive otherwise standard of care asthma and allergy treatment Standard of care: standard of care asthma and allergy treatment
Allergen Immunotherapy
n=27 participants at risk
This group receives initially weekly, later biweekly subcutaneous injections of a mixture of allergen extracts, tailored to the individual child's allergy sensitization profile. The maximum number of injections at each visit is 1-3 injections per child. In addition to allergy immunotherapy. this group receives standard of care asthma and allergy treatment Allergen extracts (subcutaneous injections): Allergy immunotherapy consists of regular subcutaneous injections of an individualized mixture of allergen extracts according to the allergy sensitization profile of each child. Increasing doses of allergen extract are given in 1-3 injections until a predetermined maintenance dose is reached. This maintenance dose varies by extract and accords to the general practice guidelines of immunotherapy. To increase safety the cumulative monthly maintenance doses are divided into biweekly visits during the maintenance phase. Standard of care: standard of care asthma and allergy treat
Skin and subcutaneous tissue disorders
Local allergic reaction after immunotherapy injectionss
0.00%
0/23 • Adverse event data was collected during the 3-year study period.
Definition: Serious adverse events= hospitalization, death In the immunotherapy group, all allergic or asthmatic events occurring the 48 hours after immunotherapy injections had been administered were considered a possible consequence of immunotherapy (immediate or late allergic reaction). Immediate type reactions were defined as any allergic reaction occurring within 2 hours after the injections.
81.5%
22/27 • Number of events 128 • Adverse event data was collected during the 3-year study period.
Definition: Serious adverse events= hospitalization, death In the immunotherapy group, all allergic or asthmatic events occurring the 48 hours after immunotherapy injections had been administered were considered a possible consequence of immunotherapy (immediate or late allergic reaction). Immediate type reactions were defined as any allergic reaction occurring within 2 hours after the injections.
Immune system disorders
Systemic allergic reactions after immunotherapy injections
0.00%
0/23 • Adverse event data was collected during the 3-year study period.
Definition: Serious adverse events= hospitalization, death In the immunotherapy group, all allergic or asthmatic events occurring the 48 hours after immunotherapy injections had been administered were considered a possible consequence of immunotherapy (immediate or late allergic reaction). Immediate type reactions were defined as any allergic reaction occurring within 2 hours after the injections.
44.4%
12/27 • Number of events 63 • Adverse event data was collected during the 3-year study period.
Definition: Serious adverse events= hospitalization, death In the immunotherapy group, all allergic or asthmatic events occurring the 48 hours after immunotherapy injections had been administered were considered a possible consequence of immunotherapy (immediate or late allergic reaction). Immediate type reactions were defined as any allergic reaction occurring within 2 hours after the injections.

Additional Information

Gabriele de Vos, M.D.

Jacobi Medical Center / Albert Einstein College of Medicine

Phone: 7184152809

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place