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

This study has been completed.
Sponsor:
Collaborator:
Immune Tolerance Network (ITN)
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00346398
First received: June 27, 2006
Last updated: June 4, 2014
Last verified: June 2014
Results First Received: August 29, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Prevention
Conditions: Asthma
Allergic Sensitization
Interventions: Biological: Oral mucosal immunoprophylaxis (OMIP)
Biological: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Subject recruitment occurred between June 2006 and July 2007 at 2 sites in Australia and 1 site in the United States

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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

Reporting Groups
  Description
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.

Participant Flow:   Overall Study
    OMIP With Timothy Grass, Cat and House Dust Mite Allergens     Placebo  
STARTED     25     26  
COMPLETED     22     24  
NOT COMPLETED     3     2  
Lost to Follow-up                 3                 0  
Withdrawal by Subject                 0                 2  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
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.
Total Total of all reporting groups

Baseline Measures
    OMIP With Timothy Grass, Cat and House Dust Mite Allergens     Placebo     Total  
Number of Participants  
[units: participants]
  25     26     51  
Age, Customized  
[units: participants]
     
Aged 12-17 Months     6     6     12  
Aged 18-23 Months     16     12     28  
Aged 24-30 Months     3     8     11  
Gender  
[units: participants]
     
Female     13     12     25  
Male     12     14     26  
Region of Enrollment  
[units: participants]
     
United States     4     4     8  
Australia     21     22     43  
Severity of Atopic Dermatitis (AD) Using SCORAD Index [1]
[units: Units on a Scale]
Mean ± Standard Deviation
  13.3  ± 8.5     11.4  ± 9.1     12.3  ± 8.8  
[1] Scoring of Atopic Dermatitis (SCORAD) disease-severity scale measures intensity of erythema, edema/papulation, oozing/crusts, excoriations, lichenification and dryness, each on a scale from 0-3 for a maximum total of 18 points. This score is multiplied by 3.5 and added to 1/5 of the affected percent body surface area. The final score is added to the score from a 0-10 point pruritus visual analog scale (VAS) and a 0-10 point loss of sleep VAS. Summary: SCORAD (0-103)=extent (0-100)/5+intensity (0-18)x3.5 + pruritus and sleep (0-20).Interpretation: SCORAD (0 (no disease) to 103 (most severe)).



  Outcome Measures
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1.  Primary:   Number of Participants With Allergic Sensitization at Month 36 Status Post Treatment Completion   [ Time Frame: Three years (36 months) after Treatment Completion ]

2.  Secondary:   Number of Participants With Current Asthma at Month 36 Status Post Treatment Completion   [ Time Frame: Three years (36 months) after Treatment Completion ]

3.  Secondary:   Time to First Onset of Asthma   [ Time Frame: From Treatment Initiation to Month 36 Status Post Treatment Completion ]


  Serious Adverse Events


  Other Adverse Events
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Time Frame Start of study through three years post-treatment (up to four years total)
Additional Description 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.

Frequency Threshold
Threshold above which other adverse events are reported   5%  

Reporting Groups
  Description
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.

Other Adverse Events
    OMIP With Timothy Grass, Cat and House Dust Mite Allergens     Placebo  
Total, other (not including serious) adverse events      
# participants affected / at risk     25/25     26/26  
Blood and lymphatic system disorders      
Lymphadenopathy † 1    
# participants affected / at risk     1/25 (4.00%)     4/26 (15.38%)  
# events     1     4  
Ear and labyrinth disorders      
Ear pain † 1    
# participants affected / at risk     1/25 (4.00%)     5/26 (19.23%)  
# events     1     6  
Eye disorders      
Conjunctivitis † 1    
# participants affected / at risk     8/25 (32.00%)     14/26 (53.85%)  
# events     23     20  
Conjunctivitis allergic † 1    
# participants affected / at risk     5/25 (20.00%)     3/26 (11.54%)  
# events     5     3  
Eye pruritus † 1    
# participants affected / at risk     3/25 (12.00%)     5/26 (19.23%)  
# events     4     12  
Lacrimation increased † 1    
# participants affected / at risk     6/25 (24.00%)     8/26 (30.77%)  
# events     11     18  
Gastrointestinal disorders      
Abdominal discomfort † 1    
# participants affected / at risk     2/25 (8.00%)     1/26 (3.85%)  
# events     3     1  
Abdominal pain upper † 1    
# participants affected / at risk     2/25 (8.00%)     1/26 (3.85%)  
# events     3     2  
Constipation † 1    
# participants affected / at risk     4/25 (16.00%)     3/26 (11.54%)  
# events     6     3  
Diarrhoea † 1    
# participants affected / at risk     17/25 (68.00%)     21/26 (80.77%)  
# events     32     57  
Oral pruritus † 1    
# participants affected / at risk     2/25 (8.00%)     1/26 (3.85%)  
# events     7     1  
Teething † 1    
# participants affected / at risk     8/25 (32.00%)     8/26 (30.77%)  
# events     10     22  
Vomiting † 1    
# participants affected / at risk     15/25 (60.00%)     18/26 (69.23%)  
# events     34     52  
General disorders      
Pyrexia † 1    
# participants affected / at risk     18/25 (72.00%)     19/26 (73.08%)  
# events     60     51  
Immune system disorders      
Allergy to animal † 1    
# participants affected / at risk     2/25 (8.00%)     3/26 (11.54%)  
# events     2     11  
Drug hypersensitivity † 1    
# participants affected / at risk     2/25 (8.00%)     1/26 (3.85%)  
# events     2     1  
Food allergy † 1    
# participants affected / at risk     9/25 (36.00%)     8/26 (30.77%)  
# events     35     20  
Hypersensitivity † 1    
# participants affected / at risk     7/25 (28.00%)     6/26 (23.08%)  
# events     28     14  
Seasonal allergy † 1    
# participants affected / at risk     4/25 (16.00%)     4/26 (15.38%)  
# events     12     5  
Infections and infestations      
Bronchitis † 1    
# participants affected / at risk     3/25 (12.00%)     1/26 (3.85%)  
# events     3     2  
Croup infectious † 1    
# participants affected / at risk     1/25 (4.00%)     2/26 (7.69%)  
# events     4     2  
Ear infection † 1    
# participants affected / at risk     10/25 (40.00%)     6/26 (23.08%)  
# events     15     17  
Gastroenteritis † 1    
# participants affected / at risk     13/25 (52.00%)     12/26 (46.15%)  
# events     30     26  
Lower respiratory tract infection † 1    
# participants affected / at risk     3/25 (12.00%)     4/26 (15.38%)  
# events     9     7  
Nasopharyngitis † 1    
# participants affected / at risk     21/25 (84.00%)     23/26 (88.46%)  
# events     141     145  
Otitis media † 1    
# participants affected / at risk     4/25 (16.00%)     3/26 (11.54%)  
# events     14     4  
Otitis media acute † 1    
# participants affected / at risk     3/25 (12.00%)     4/26 (15.38%)  
# events     5     7  
Pharyngitis † 1    
# participants affected / at risk     1/25 (4.00%)     3/26 (11.54%)  
# events     1     4  
Respiratory tract infection viral † 1    
# participants affected / at risk     3/25 (12.00%)     2/26 (7.69%)  
# events     4     7  
Rhinitis † 1    
# participants affected / at risk     7/25 (28.00%)     5/26 (19.23%)  
# events     18     9  
Tonsillitis † 1    
# participants affected / at risk     7/25 (28.00%)     7/26 (26.92%)  
# events     11     17  
Upper respiratory tract infection † 1    
# participants affected / at risk     22/25 (88.00%)     24/26 (92.31%)  
# events     192     184  
Urinary tract infection † 1    
# participants affected / at risk     3/25 (12.00%)     3/26 (11.54%)  
# events     5     6  
Varicella † 1    
# participants affected / at risk     2/25 (8.00%)     6/26 (23.08%)  
# events     2     6  
Viral infection † 1    
# participants affected / at risk     12/25 (48.00%)     10/26 (38.46%)  
# events     36     26  
Injury, poisoning and procedural complications      
Arthropod bite † 1    
# participants affected / at risk     4/25 (16.00%)     3/26 (11.54%)  
# events     6     5  
Fall † 1    
# participants affected / at risk     4/25 (16.00%)     1/26 (3.85%)  
# events     5     1  
Musculoskeletal and connective tissue disorders      
Pain in extremity † 1    
# participants affected / at risk     2/25 (8.00%)     3/26 (11.54%)  
# events     2     3  
Nervous system disorders      
Febrile convulsion † 1    
# participants affected / at risk     2/25 (8.00%)     1/26 (3.85%)  
# events     5     2  
Headache † 1    
# participants affected / at risk     4/25 (16.00%)     4/26 (15.38%)  
# events     5     11  
Respiratory, thoracic and mediastinal disorders      
Asthma † 1    
# participants affected / at risk     8/25 (32.00%)     4/26 (15.38%)  
# events     25     10  
Cough † 1    
# participants affected / at risk     21/25 (84.00%)     20/26 (76.92%)  
# events     111     83  
Epistaxis † 1    
# participants affected / at risk     3/25 (12.00%)     3/26 (11.54%)  
# events     14     8  
Nasal congestion † 1    
# participants affected / at risk     11/25 (44.00%)     12/26 (46.15%)  
# events     27     48  
Oropharyngeal pain † 1    
# participants affected / at risk     6/25 (24.00%)     2/26 (7.69%)  
# events     11     4  
Rhinorrhoea † 1    
# participants affected / at risk     20/25 (80.00%)     20/26 (76.92%)  
# events     82     99  
Sneezing † 1    
# participants affected / at risk     11/25 (44.00%)     8/26 (30.77%)  
# events     33     20  
Stridor † 1    
# participants affected / at risk     2/25 (8.00%)     1/26 (3.85%)  
# events     7     1  
Tonsillar hypertrophy † 1    
# participants affected / at risk     3/25 (12.00%)     2/26 (7.69%)  
# events     4     2  
Wheezing † 1    
# participants affected / at risk     11/25 (44.00%)     10/26 (38.46%)  
# events     62     31  
Skin and subcutaneous tissue disorders      
Dermatitis diaper † 1    
# participants affected / at risk     3/25 (12.00%)     0/26 (0.00%)  
# events     4     0  
Eczema † 1    
# participants affected / at risk     11/25 (44.00%)     7/26 (26.92%)  
# events     25     12  
Erythema † 1    
# participants affected / at risk     2/25 (8.00%)     1/26 (3.85%)  
# events     2     4  
Pruritus † 1    
# participants affected / at risk     4/25 (16.00%)     2/26 (7.69%)  
# events     12     3  
Rash † 1    
# participants affected / at risk     8/25 (32.00%)     6/26 (23.08%)  
# events     20     6  
Urticaria † 1    
# participants affected / at risk     9/25 (36.00%)     6/26 (23.08%)  
# events     28     9  
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA 11.1



  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
One participant in the placebo group could not be included in intent-to-treat analyses because a sibling was also in the study


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