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A Randomized, Double-Blind Placebo-Controlled Peanut Sublingual Immunotherapy Trial

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Consortium of Food Allergy Research
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00580606
First received: December 18, 2007
Last updated: May 23, 2013
Last verified: May 2013
Results First Received: September 28, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Crossover Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator);   Primary Purpose: Treatment
Conditions: Food Hypersensitivity
Hypersensitivity
Immediate Hypersensitivity
Peanut Hypersensitivity
Interventions: Drug: Glycerinated peanut allergenic extract
Drug: Placebo for peanut extract (glycerin)

  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
Recruitment took place at five university-based medical centers in the United States (Mt. Sinai School of Medicine, Johns Hopkins University, Duke University, National Jewish Medical Center, University of Arkansas Children's Hospital from April 2008 to January 2010.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Low Dose Peanut SLIT (Double Blind to Open Label) Subjects ingest peanut protein (glycerinated peanut allergenic extract) daily starting with 0.000165 mcg, followed by a build-up phase (escalating peanut doses every 2 weeks, achieving maintenance dose by 36 weeks). Thereafter, subjects are on a maximally tolerated maintenance dose (165 mcg to 1,386 mcg) for >= 8 weeks. After Week 44, subjects are given a 5,000 mg Oral Food Challenge (OFC) using peanut powder. Subjects/study staff are unblinded following this OFC and continue on an open label peanut protein maintenance dose of 1,386 mcg/day or may attempt escalation up to this dose. Subjects who at the Week 116 OFC are unable to consume >= 5,000 mg peanut powder or 10-fold the amount of peanut powder compared to the baseline OFC will discontinue study therapy. SLIT=Sublingual Immunotherapy
Placebo (DB) Crossed Over to High Dose Peanut SLIT (OL) Subjects ingest placebo (glycerin) daily beginning with a dose of 0.000165 mcg, followed by a build-up phase (escalating placebo doses every 2 weeks, achieving a maintenance dose by 36 weeks). Thereafter, subjects are on a maximally tolerated maintenance dose (165 mcg to 1,386 mcg) for >= 8 weeks. After Week 44, subjects are given a 5,000 mg Oral Food Challenge (OFC) using peanut powder. Subjects/study staff are unblinded following this OFC and subjects no longer receive placebo dosing but are crossed over and receive open label high dose peanut SLIT; the study procedures and schedule are the same as for the Low Dose Peanut SLIT group, the only difference is the maximum maintenance dose is almost 3-fold higher at 3,696 mcg/day. DB=Double Blind, SLIT=Sublingual Immunotherapy, OL=Open Label.

Participant Flow for 2 periods

Period 1:   Double Blind (DB)
    Low Dose Peanut SLIT (Double Blind to Open Label)     Placebo (DB) Crossed Over to High Dose Peanut SLIT (OL)  
STARTED     20     20  
Had Week 44 Oral Food Challenge     18     19  
COMPLETED     20 [1]   20 [1]
NOT COMPLETED     0     0  
[1] Completed: Participants who were assessed for the primary outcome measure.

Period 2:   Open Label (OL)
    Low Dose Peanut SLIT (Double Blind to Open Label)     Placebo (DB) Crossed Over to High Dose Peanut SLIT (OL)  
STARTED     18 [1]   17 [2]
COMPLETED     2 [3]   0 [3]
NOT COMPLETED     16     17  
Currently Dosing                 8                 10  
Withdrawal by Subject                 5                 3  
Lack of Efficacy                 2                 0  
Physician Decision                 1                 1  
Adverse Event                 0                 1  
Lost to Follow-up                 0                 1  
Pregnancy                 0                 1  
[1] 2 participants discontinued dosing before Week 44 OFC.
[2] 1 participant discontinued dosing before Wk 44 OFC; 2 passed Wk 44 OFC & ineligible for crossover.
[3] Completed: Participants who have completed dosing and final OFC.



  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
Low Dose Peanut SLIT (Double Blind to Open Label) Subjects ingest peanut protein (glycerinated peanut allergenic extract) daily starting with 0.000165 mcg, followed by a build-up phase (escalating peanut doses every 2 weeks, achieving maintenance dose by 36 weeks). Thereafter, subjects are on a maximally tolerated maintenance dose (165 mcg to 1,386 mcg) for >= 8 weeks. After Week 44, subjects are given a 5,000 mg Oral Food Challenge (OFC) using peanut powder. Subjects/study staff are unblinded following this OFC and continue on an open label peanut protein maintenance dose of 1,386 mcg/day or may attempt escalation up to this dose. Subjects who at the Week 116 OFC are unable to consume >= 5,000 mg peanut powder or 10-fold the amount of peanut powder compared to the baseline OFC will discontinue study therapy. SLIT=Sublingual Immunotherapy
Placebo (DB) Crossed Over to High Dose Peanut SLIT (OL) Subjects ingest placebo (glycerin) daily beginning with a dose of 0.000165 mcg, followed by a build-up phase (escalating placebo doses every 2 weeks, achieving a maintenance dose by 36 weeks). Thereafter, subjects are on a maximally tolerated maintenance dose (165 mcg to 1,386 mcg) for >= 8 weeks. After Week 44, subjects are given a 5,000 mg Oral Food Challenge (OFC) using peanut powder. Subjects/study staff are unblinded following this OFC and subjects no longer receive placebo dosing but are crossed over and receive open label high dose peanut SLIT; the study procedures and schedule are the same as for the Low Dose Peanut SLIT group, the only difference is the maximum maintenance dose is almost 3-fold higher at 3,696 mcg/day. DB=Double Blind, SLIT=Sublingual Immunotherapy, OL=Open Label.
Total Total of all reporting groups

Baseline Measures
    Low Dose Peanut SLIT (Double Blind to Open Label)     Placebo (DB) Crossed Over to High Dose Peanut SLIT (OL)     Total  
Number of Participants  
[units: participants]
  20     20     40  
Age  
[units: participants]
     
<=18 years     15     15     30  
Between 18 and 65 years     5     5     10  
>=65 years     0     0     0  
Age  
[units: years]
Mean ± Standard Deviation
  17.2  ± 7.6     16.5  ± 3.5     16.8  ± 5.8  
Gender  
[units: participants]
     
Female     7     6     13  
Male     13     14     27  
Ethnicity (NIH/OMB)  
[units: Participants]
     
Hispanic or Latino     0     0     0  
Not Hispanic or Latino     20     20     40  
Unknown or Not Reported     0     0     0  
Race (NIH/OMB)  
[units: Participants]
     
American Indian or Alaska Native     0     0     0  
Asian     2     1     3  
Native Hawaiian or Other Pacific Islander     0     0     0  
Black or African American     1     0     1  
White     17     19     36  
More than one race     0     0     0  
Unknown or Not Reported     0     0     0  
Region of Enrollment  
[units: participants]
     
United States     20     20     40  
Atopic Dermatitis Total Score [1]
[units: Scores on a scale]
Mean ± Standard Deviation
  1.1  ± 1.7     0.9  ± 1.6     1.0  ± 1.6  
Total IgE [2]
[units: kU/L]
Mean ± Standard Deviation
  407.8  ± 254.1     330.5  ± 305.0     369.1  ± 279.9  
Peanut IgE [3]
[units: kUA/L]
Mean ± Standard Deviation
  33.6  ± 38.1     47.1  ± 58.0     40.4  ± 48.9  
Peanut Skin Prick Test Score [4]
[units: mm]
Mean ± Standard Deviation
  14.0  ± 6.9     12.4  ± 4.6     13.2  ± 5.9  
Age at Initial Peanut Allergic Reaction [5]
[units: years]
Mean ± Standard Deviation
  4.6  ± 6.9     1.9  ± 1.5     3.3  ± 5.2  
[1] The Atopic Dermatitis Total Score is scored on a 10 point scale of 0 to 9 where a higher score indicates increasing severity of atopic dermatitis. This score is a combination of three scores that range from 0 to 3 in the following areas: body surface area score, disease course, and disease intensity.
[2] Total amount of serum immunoglobulin E. Individuals who are not allergic may have a total IgE as high as 304 kU/L.
[3] Amount of serum peanut-specific immunoglobulin E. Individuals with a peanut IgE of <0.35 kUA/L are considered not to be sensitized to peanut.
[4] This score is calculated by subtracting the size of the saline wheal (in mm) from the size of the peanut wheal (in mm) observed for a skin prick test. Individuals with a peanut skin prick test score of < 3 mm are considered to have a negative result. 1 subject in the Placebo group did not have a value for this measure.
[5] Two subjects in the Placebo group did not have a value for this measure.



  Outcome Measures
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1.  Primary:   Percent of Participants Who Successfully Consumed 5,000 mg of Peanut Powder or at Least a 10-fold Increase in the Amount of Peanut Powder Compared to Their Baseline Oral Food Challenge   [ Time Frame: Week 44 (Double Blind Period) ]
  Hide Outcome Measure 1

Measure Type Primary
Measure Title Percent of Participants Who Successfully Consumed 5,000 mg of Peanut Powder or at Least a 10-fold Increase in the Amount of Peanut Powder Compared to Their Baseline Oral Food Challenge
Measure Description Desensitization Assessment: Participants who successfully consumed without dose-limiting symptoms 5,000 mg of peanut powder or at least a 10-fold increase in the amount of peanut powder compared to their baseline oral food challenge during a double-blind placebo-controlled oral food challenge were counted as successes.
Time Frame Week 44 (Double Blind Period)  
Safety Issue No  

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.
The intention to treat (ITT) population was used which included all subjects randomized to double-blind treatment.

Reporting Groups
  Description
Low Dose Peanut SLIT (Double Blind) Subjects ingest peanut protein (glycerinated peanut allergenic extract) daily starting with 0.000165 mcg, followed by a build-up phase (escalating peanut doses every 2 weeks, achieving maintenance dose by 36 weeks). Thereafter, subjects are on a maximally tolerated maintenance dose (165 mcg to 1,386 mcg) for >= 8 weeks. After Week 44, subjects are given a 5,000 mg Oral Food Challenge (OFC) using peanut powder. Subjects/study staff are unblinded following this OFC and continue on an open label peanut protein maintenance dose of 1,386 mcg/day or may attempt escalation up to this dose. SLIT=Sublingual Immunotherapy, mcg=microgram
Placebo (Double Blind) Subjects ingest placebo (glycerin) daily beginning with a dose of 0.000165 mcg, followed by a build-up phase (escalating placebo doses every 2 weeks, achieving a maintenance dose by 36 weeks). Thereafter, subjects are on a maximally tolerated maintenance dose (165 mcg to 1,386 mcg) for >= 8 weeks. After Week 44, subjects are given a 5,000 mg Oral Food Challenge (OFC) using peanut powder. Subjects/study staff are unblinded following this OFC and subjects no longer receive placebo dosing but are crossed over into the High Dose Peanut SLIT Crossover (Open Label) group. SLIT=Sublingual Immunotherapy, mcg=microgram

Measured Values
    Low Dose Peanut SLIT (Double Blind)     Placebo (Double Blind)  
Number of Participants Analyzed  
[units: participants]
  20     20  
Percent of Participants Who Successfully Consumed 5,000 mg of Peanut Powder or at Least a 10-fold Increase in the Amount of Peanut Powder Compared to Their Baseline Oral Food Challenge  
[units: Percentage of participants]
  70     15  


Statistical Analysis 1 for Percent of Participants Who Successfully Consumed 5,000 mg of Peanut Powder or at Least a 10-fold Increase in the Amount of Peanut Powder Compared to Their Baseline Oral Food Challenge
Groups [1] All groups
Method [2] Barnard's Statistic
P Value [3] <0.001
Risk Difference (RD) [4] 55
95% Confidence Interval ( 22.2 to 77.6 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Number of participants who successfully consumed 5,000 mg of peanut powder or at least a 10-fold increase in the amount of peanut powder compared to their baseline OFC was compared using Barnard's Statistic with the null hypothesis that there was no difference between treatment groups.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  The a priori threshold for statistical significance is 0.05.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No adjustments were made to the p-value.
[4] Other relevant estimation information:
  No text entered.



2.  Secondary:   Percent of Participants Who Achieved a Maintenance Dose of 1,386 Mcg   [ Time Frame: Week 44 (Double Blind Period) ]

3.  Secondary:   Percent of Crossover Participants Who Successfully Consumed 5,000 mg of Peanut Powder or at Least a 10-fold Increase in the Amount of Peanut Powder Compared to Their Baseline Oral Food Challenge After 44 Weeks of Open Label Peanut Protein Consumption   [ Time Frame: Week 44 after initiating crossover open label peanut protein consumption ]

4.  Secondary:   Percent of Crossover Participants Who Achieved an Open Label Peanut Protein Consumption Maintenance Dose of 3,696 Mcg   [ Time Frame: Week 44 after initiating crossover open label peanut protein consumption ]

5.  Secondary:   Number of Participants With Serious Adverse Events (SAEs)   [ Time Frame: Baseline through Week 44 (Double Blind Period) ]

6.  Secondary:   Number of Crossover Participants With Serious Adverse Events (SAEs) During 44 Weeks of Open Label Peanut Protein Consumption   [ Time Frame: Initiation of open label peanut protein study therapy through Week 44 of open label peanut protein consumption ]

7.  Secondary:   Percent of Participants Who Successfully Consumed 10,000 mg of Peanut Powder   [ Time Frame: Approximately 8 weeks after discontinuing study therapy after 3 years on maintenance study therapy ]
Results not yet reported.   Anticipated Reporting Date:   06/2014   Safety Issue:   No


  Serious Adverse Events


  Other Adverse Events


  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
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