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

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: April 30, 2015
Last verified: April 2015
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 
Overall Participants Analyzed 
[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 (100.00%)   26/26 (100.00%) 
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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