Trial Outcomes & Findings for Promoting Tolerance to Common Allergens in High-Risk Children: Global Prevention of Asthma in Children (GPAC) Study (NCT NCT00346398)

Last Updated: 2017-05-01

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

51 participants

Primary outcome timeframe

Three years (36 months) after Treatment Completion

Results posted on

2017-05-01

Participant Flow

Subject recruitment occurred between June 2006 and July 2007 at 2 sites in Australia and 1 site in the United States

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

Participant milestones

Participant milestones
Measure	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.	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.
Overall Study STARTED	25	26
Overall Study COMPLETED	22	24
Overall Study NOT COMPLETED	3	2

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.
Overall Study Lost to Follow-up	3	0
Overall Study Withdrawal by Subject	0	2

Baseline Characteristics

Promoting Tolerance to Common Allergens in High-Risk Children: Global Prevention of Asthma in Children (GPAC) Study

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	OMIP With Timothy Grass, Cat and House Dust Mite Allergens n=25 Participants 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.	Placebo n=26 Participants 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.	Total n=51 Participants Total of all reporting groups
Age, Customized Aged 12-17 Months	6 participants n=99 Participants	6 participants n=107 Participants	12 participants n=206 Participants
Age, Customized Aged 18-23 Months	16 participants n=99 Participants	12 participants n=107 Participants	28 participants n=206 Participants
Age, Customized Aged 24-30 Months	3 participants n=99 Participants	8 participants n=107 Participants	11 participants n=206 Participants
Sex: Female, Male Female	13 Participants n=99 Participants	12 Participants n=107 Participants	25 Participants n=206 Participants
Sex: Female, Male Male	12 Participants n=99 Participants	14 Participants n=107 Participants	26 Participants n=206 Participants
Region of Enrollment United States	4 participants n=99 Participants	4 participants n=107 Participants	8 participants n=206 Participants
Region of Enrollment Australia	21 participants n=99 Participants	22 participants n=107 Participants	43 participants n=206 Participants
Severity of Atopic Dermatitis (AD) Using SCORAD Index	13.3 Units on a Scale STANDARD_DEVIATION 8.5 • n=99 Participants	11.4 Units on a Scale STANDARD_DEVIATION 9.1 • n=107 Participants	12.3 Units on a Scale STANDARD_DEVIATION 8.8 • n=206 Participants

PRIMARY outcome

Timeframe: Three years (36 months) after Treatment Completion

Population: Intent-to-treat minus one participant in placebo group who had a sibling in trial

Outcome measures

Outcome measures
Measure	OMIP With Timothy Grass, Cat and House Dust Mite Allergens n=25 Participants 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.	Placebo n=25 Participants 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.
Number of Participants With Allergic Sensitization at Month 36 Status Post Treatment Completion	22 participants	19 participants

SECONDARY outcome

Timeframe: Three years (36 months) after Treatment Completion

Population: Intent-to-treat minus one participant in placebo group who had a sibling in trial

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.

Outcome measures

Outcome measures
Measure	OMIP With Timothy Grass, Cat and House Dust Mite Allergens n=25 Participants 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.	Placebo n=25 Participants 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.
Number of Participants With Current Asthma at Month 36 Status Post Treatment Completion	4 participants	4 participants

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure	OMIP With Timothy Grass, Cat and House Dust Mite Allergens n=25 Participants 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.	Placebo n=25 Participants 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.
Time to First Onset of Asthma	31.0 Months Standard Error 1.9	38.3 Months Standard Error 2.1

Adverse Events

OMIP With Timothy Grass, Cat and House Dust Mite Allergens

Serious events: 8 serious events

Other events: 25 other events

Deaths: 0 deaths

Placebo

Serious events: 7 serious events

Other events: 26 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Director, Clinical Research Operations Program

DAIT/NIAID

Phone: 301-594-7669

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	OMIP With Timothy Grass, Cat and House Dust Mite Allergens n=25 participants at risk 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.	Placebo n=26 participants at risk 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.
Ear and labyrinth disorders Conductive deafness	0.00% 0/25 • Start of study through three years post-treatment (up to four years total) This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003). One participant in the placebo group is included in adverse event reports, but excluded from further analysis.	3.8% 1/26 • Number of events 1 • Start of study through three years post-treatment (up to four years total) This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003). One participant in the placebo group is included in adverse event reports, but excluded from further analysis.
Immune system disorders Anaphylactic reaction	4.0% 1/25 • Number of events 1 • Start of study through three years post-treatment (up to four years total) This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003). One participant in the placebo group is included in adverse event reports, but excluded from further analysis.	0.00% 0/26 • Start of study through three years post-treatment (up to four years total) This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003). One participant in the placebo group is included in adverse event reports, but excluded from further analysis.
Infections and infestations Acute tonsillitis	4.0% 1/25 • Number of events 1 • Start of study through three years post-treatment (up to four years total) This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003). One participant in the placebo group is included in adverse event reports, but excluded from further analysis.	0.00% 0/26 • Start of study through three years post-treatment (up to four years total) This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003). One participant in the placebo group is included in adverse event reports, but excluded from further analysis.
Infections and infestations Ear infection	0.00% 0/25 • Start of study through three years post-treatment (up to four years total) This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003). One participant in the placebo group is included in adverse event reports, but excluded from further analysis.	7.7% 2/26 • Number of events 2 • Start of study through three years post-treatment (up to four years total) This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003). One participant in the placebo group is included in adverse event reports, but excluded from further analysis.
Infections and infestations Gastroenteritis viral	0.00% 0/25 • Start of study through three years post-treatment (up to four years total) This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003). One participant in the placebo group is included in adverse event reports, but excluded from further analysis.	3.8% 1/26 • Number of events 1 • Start of study through three years post-treatment (up to four years total) This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003). One participant in the placebo group is included in adverse event reports, but excluded from further analysis.
Infections and infestations Tonsillitis	4.0% 1/25 • Number of events 1 • Start of study through three years post-treatment (up to four years total) This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003). One participant in the placebo group is included in adverse event reports, but excluded from further analysis.	3.8% 1/26 • Number of events 1 • Start of study through three years post-treatment (up to four years total) This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003). One participant in the placebo group is included in adverse event reports, but excluded from further analysis.
Injury, poisoning and procedural complications Joint dislocation	4.0% 1/25 • Number of events 1 • Start of study through three years post-treatment (up to four years total) This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003). One participant in the placebo group is included in adverse event reports, but excluded from further analysis.	0.00% 0/26 • Start of study through three years post-treatment (up to four years total) This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003). One participant in the placebo group is included in adverse event reports, but excluded from further analysis.
Injury, poisoning and procedural complications Skin laceration	0.00% 0/25 • Start of study through three years post-treatment (up to four years total) This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003). One participant in the placebo group is included in adverse event reports, but excluded from further analysis.	3.8% 1/26 • Number of events 1 • Start of study through three years post-treatment (up to four years total) This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003). One participant in the placebo group is included in adverse event reports, but excluded from further analysis.
Injury, poisoning and procedural complications Tooth fracture	0.00% 0/25 • Start of study through three years post-treatment (up to four years total) This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003). One participant in the placebo group is included in adverse event reports, but excluded from further analysis.	3.8% 1/26 • Number of events 1 • Start of study through three years post-treatment (up to four years total) This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003). One participant in the placebo group is included in adverse event reports, but excluded from further analysis.
Psychiatric disorders Breathing-related sleep disorder	4.0% 1/25 • Number of events 1 • Start of study through three years post-treatment (up to four years total) This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003). One participant in the placebo group is included in adverse event reports, but excluded from further analysis.	0.00% 0/26 • Start of study through three years post-treatment (up to four years total) This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003). One participant in the placebo group is included in adverse event reports, but excluded from further analysis.
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/25 • Start of study through three years post-treatment (up to four years total) This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003). One participant in the placebo group is included in adverse event reports, but excluded from further analysis.	3.8% 1/26 • Number of events 2 • Start of study through three years post-treatment (up to four years total) This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003). One participant in the placebo group is included in adverse event reports, but excluded from further analysis.
Respiratory, thoracic and mediastinal disorders Bronchial hyperreactivity	4.0% 1/25 • Number of events 1 • Start of study through three years post-treatment (up to four years total) This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003). One participant in the placebo group is included in adverse event reports, but excluded from further analysis.	0.00% 0/26 • Start of study through three years post-treatment (up to four years total) This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003). One participant in the placebo group is included in adverse event reports, but excluded from further analysis.
Respiratory, thoracic and mediastinal disorders Sleep apnoea syndrome	4.0% 1/25 • Number of events 1 • Start of study through three years post-treatment (up to four years total) This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003). One participant in the placebo group is included in adverse event reports, but excluded from further analysis.	0.00% 0/26 • Start of study through three years post-treatment (up to four years total) This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003). One participant in the placebo group is included in adverse event reports, but excluded from further analysis.
Respiratory, thoracic and mediastinal disorders Tonsillar hypertrophy	4.0% 1/25 • Number of events 1 • Start of study through three years post-treatment (up to four years total) This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003). One participant in the placebo group is included in adverse event reports, but excluded from further analysis.	0.00% 0/26 • Start of study through three years post-treatment (up to four years total) This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003). One participant in the placebo group is included in adverse event reports, but excluded from further analysis.
Respiratory, thoracic and mediastinal disorders Wheezing	0.00% 0/25 • Start of study through three years post-treatment (up to four years total) This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003). One participant in the placebo group is included in adverse event reports, but excluded from further analysis.	3.8% 1/26 • Number of events 1 • Start of study through three years post-treatment (up to four years total) This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003). One participant in the placebo group is included in adverse event reports, but excluded from further analysis.
Skin and subcutaneous tissue disorders Eczema	4.0% 1/25 • Number of events 1 • Start of study through three years post-treatment (up to four years total) This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003). One participant in the placebo group is included in adverse event reports, but excluded from further analysis.	0.00% 0/26 • Start of study through three years post-treatment (up to four years total) This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003). One participant in the placebo group is included in adverse event reports, but excluded from further analysis.