Trial Outcomes & Findings for Sublingual Immunotherapy for Peanut Allergy and Induction of Tolerance (NCT NCT01373242)
NCT ID: NCT01373242
Last Updated: 2019-06-12
Results Overview
An estimate of the dose as assessed by the 48th month DBPCFC reported in mg peanut protein, also called population sensitization threshold, predicted to provoke reactions in 5% of the peanut-allergic population. This will also give population level no observed adverse event level (NOAEL) and lowest observed adverse event level (LOAEL) that would define interval of consecutive administered dose levels within which the population sensitization threshold lies. NOAEL is the highest dose observed not to produce any adverse effect and LOAEL is the lowest dose that is observed to produce an adverse effect.
COMPLETED
PHASE1/PHASE2
54 participants
48 - 52 months
2019-06-12
Participant Flow
Peanut allergic children ages 1-11 years
Participant milestones
| Measure |
Peanut (Liquid Peanut Extract) SLIT
All subjects will receive peanut SLIT upon enrollment for at least 48 months and then undergo a desensitization DBPCFC. Subjects will then be randomized to be off treatment for a period between 1 to 17 weeks. Subjects will then undergo a final DBPCFC.
Liquid peanut extract (Peanut SLIT): Liquid peanut extract will be administered under the tongue
|
|---|---|
|
Overall Study
STARTED
|
54
|
|
Overall Study
COMPLETED
|
38
|
|
Overall Study
NOT COMPLETED
|
16
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Sublingual Immunotherapy for Peanut Allergy and Induction of Tolerance
Baseline characteristics by cohort
| Measure |
Peanut ( Liquid Peanut Extract) SLIT
n=54 Participants
All subjects will receive peanut SLIT upon enrollment for at least the first 48 months. After the desensitization DBPCFC after at least 48 months of treatment, subjects will be randomized off treatment from 1 to 17 weeks. Subjects will then undergo another DBPCFC.
Liquid peanut extract (Peanut SLIT): Liquid peanut extract will be administered under the tongue
|
|---|---|
|
Age, Categorical
<=18 years
|
54 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
7.05 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
20 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
34 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
4 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
49 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
54 Participants
n=5 Participants
|
|
Peanut-specific IgE (kU/L)
|
85.6 kU/L
n=5 Participants
|
|
Peanut skin prick test wheal size (mm)
|
16 mm
n=5 Participants
|
PRIMARY outcome
Timeframe: 48 - 52 monthsAn estimate of the dose as assessed by the 48th month DBPCFC reported in mg peanut protein, also called population sensitization threshold, predicted to provoke reactions in 5% of the peanut-allergic population. This will also give population level no observed adverse event level (NOAEL) and lowest observed adverse event level (LOAEL) that would define interval of consecutive administered dose levels within which the population sensitization threshold lies. NOAEL is the highest dose observed not to produce any adverse effect and LOAEL is the lowest dose that is observed to produce an adverse effect.
Outcome measures
| Measure |
Peanut (Liquid Peanut Extract) SLIT
n=54 Participants
All subjects will receive peanut SLIT upon enrollment for at least 48 months and then undergo a desensitization DBPCFC. Subjects will then be randomized to be off treatment for a period between 1 to 17 weeks. Subjects will then undergo a final DBPCFC.
Liquid peanut extract (Peanut SLIT): Liquid peanut extract will be administered under the tongue
|
Non-desensitized After Peanut SLIT
All subjects will receive peanut SLIT upon enrollment for at least 48 months and then undergo a desensitization DBPCFC. 'Non-desensitized' defined as experiencing dose limiting symptoms during the 5000mg desensitization DBPCFC.
|
|---|---|---|
|
Population Sensitization Threshold in mg Peanut Protein Predicted to Provoke Reactions in 5% of the Peanut-allergic Population
NOAEL threshold
|
160 mg
|
—
|
|
Population Sensitization Threshold in mg Peanut Protein Predicted to Provoke Reactions in 5% of the Peanut-allergic Population
LOAEL threshold
|
300 mg
|
—
|
PRIMARY outcome
Timeframe: 48-52 monthsAn estimate of the dose as assessed by the 48th month DBPCFC reported in mg peanut protein, also called population sensitization threshold, predicted to provoke reactions in 10% of the peanut-allergic population. This will also give population level no observed adverse event level (NOAEL) and lowest observed adverse event level (LOAEL) that would define interval of consecutive administered dose levels within which the population sensitization threshold lies. NOAEL is the highest dose observed not to produce any adverse effect and LOAEL is the lowest dose that is observed to produce an adverse effect.
Outcome measures
| Measure |
Peanut (Liquid Peanut Extract) SLIT
n=54 Participants
All subjects will receive peanut SLIT upon enrollment for at least 48 months and then undergo a desensitization DBPCFC. Subjects will then be randomized to be off treatment for a period between 1 to 17 weeks. Subjects will then undergo a final DBPCFC.
Liquid peanut extract (Peanut SLIT): Liquid peanut extract will be administered under the tongue
|
Non-desensitized After Peanut SLIT
All subjects will receive peanut SLIT upon enrollment for at least 48 months and then undergo a desensitization DBPCFC. 'Non-desensitized' defined as experiencing dose limiting symptoms during the 5000mg desensitization DBPCFC.
|
|---|---|---|
|
Population Sensitization Threshold in mg Peanut Protein Predicted to Provoke Reactions in 10% of the Peanut-allergic Population
NOAEL threshold
|
800 mg
|
—
|
|
Population Sensitization Threshold in mg Peanut Protein Predicted to Provoke Reactions in 10% of the Peanut-allergic Population
LOAEL threshold
|
750 mg
|
—
|
PRIMARY outcome
Timeframe: 52 monthsA population estimate of time to loss of desensitization will be calculated for a subject's true sensitivity threshold (LOAEL) to reduce by half, also called half-life of sensitivity threshold. This is calculated based on the Kaplan-Meier estimator of the survival function using study participant data.
Outcome measures
| Measure |
Peanut (Liquid Peanut Extract) SLIT
n=54 Participants
All subjects will receive peanut SLIT upon enrollment for at least 48 months and then undergo a desensitization DBPCFC. Subjects will then be randomized to be off treatment for a period between 1 to 17 weeks. Subjects will then undergo a final DBPCFC.
Liquid peanut extract (Peanut SLIT): Liquid peanut extract will be administered under the tongue
|
Non-desensitized After Peanut SLIT
All subjects will receive peanut SLIT upon enrollment for at least 48 months and then undergo a desensitization DBPCFC. 'Non-desensitized' defined as experiencing dose limiting symptoms during the 5000mg desensitization DBPCFC.
|
|---|---|---|
|
Population Estimate of Time for a Subject's True Sensitivity Threshold to Reduce by Half.
|
17 weeks
|
—
|
PRIMARY outcome
Timeframe: 52 monthsA population estimate of time to loss of desensitization will be calculated for a subject's true sensitivity threshold (LOAEL) to maintain at the same dose level during the double-blind, placebo-controlled food challenge. Food challenge dose levels are as follows: 100 mg, 200 mg, 500 mg, 800 mg, 1300 mg, 2100 mg. This is calculated based on the Kaplan-Meier estimator of the survival function using study participant data.
Outcome measures
| Measure |
Peanut (Liquid Peanut Extract) SLIT
n=54 Participants
All subjects will receive peanut SLIT upon enrollment for at least 48 months and then undergo a desensitization DBPCFC. Subjects will then be randomized to be off treatment for a period between 1 to 17 weeks. Subjects will then undergo a final DBPCFC.
Liquid peanut extract (Peanut SLIT): Liquid peanut extract will be administered under the tongue
|
Non-desensitized After Peanut SLIT
All subjects will receive peanut SLIT upon enrollment for at least 48 months and then undergo a desensitization DBPCFC. 'Non-desensitized' defined as experiencing dose limiting symptoms during the 5000mg desensitization DBPCFC.
|
|---|---|---|
|
Population Estimate of a Subject's True Sensitivity Threshold to Maintain at the Same Dose Level During DBPCFC
|
13 weeks
|
—
|
PRIMARY outcome
Timeframe: 52 monthsA population estimate of time to loss of desensitization will be calculated for a subject's true sensitivity threshold (LOAEL) to decrease by one dose level during the double-blind, placebo-controlled food challenge. Food challenge dose levels are as follows: 100 mg, 200 mg, 500 mg, 800 mg, 1300 mg, 2100 mg. This is calculated based on the Kaplan-Meier estimator of the survival function using study participant data.
Outcome measures
| Measure |
Peanut (Liquid Peanut Extract) SLIT
n=54 Participants
All subjects will receive peanut SLIT upon enrollment for at least 48 months and then undergo a desensitization DBPCFC. Subjects will then be randomized to be off treatment for a period between 1 to 17 weeks. Subjects will then undergo a final DBPCFC.
Liquid peanut extract (Peanut SLIT): Liquid peanut extract will be administered under the tongue
|
Non-desensitized After Peanut SLIT
All subjects will receive peanut SLIT upon enrollment for at least 48 months and then undergo a desensitization DBPCFC. 'Non-desensitized' defined as experiencing dose limiting symptoms during the 5000mg desensitization DBPCFC.
|
|---|---|---|
|
Population Estimate of a Subject's True Sensitivity Threshold to Decrease by One Dose Level of During the DBPCFC
|
14 weeks
|
—
|
SECONDARY outcome
Timeframe: 48 monthsNumber of participants with adverse events (AEs) and serious adverse events (SAEs) during the SLIT treatment portion of the study.
Outcome measures
| Measure |
Peanut (Liquid Peanut Extract) SLIT
n=54 Participants
All subjects will receive peanut SLIT upon enrollment for at least 48 months and then undergo a desensitization DBPCFC. Subjects will then be randomized to be off treatment for a period between 1 to 17 weeks. Subjects will then undergo a final DBPCFC.
Liquid peanut extract (Peanut SLIT): Liquid peanut extract will be administered under the tongue
|
Non-desensitized After Peanut SLIT
All subjects will receive peanut SLIT upon enrollment for at least 48 months and then undergo a desensitization DBPCFC. 'Non-desensitized' defined as experiencing dose limiting symptoms during the 5000mg desensitization DBPCFC.
|
|---|---|---|
|
Number of Participants With Adverse Events and Serious Adverse Events During the Study.
Adverse events
|
53 Participants
|
—
|
|
Number of Participants With Adverse Events and Serious Adverse Events During the Study.
Serious adverse events
|
0 Participants
|
—
|
SECONDARY outcome
Timeframe: 48 monthsWith published concerns for the development of eosinophilic gastrointestinal disease after food immunotherapy, will report the number of participants with gastrointestinal and possible gastrointestinal eosinophilic adverse events during SLIT therapy
Outcome measures
| Measure |
Peanut (Liquid Peanut Extract) SLIT
n=54 Participants
All subjects will receive peanut SLIT upon enrollment for at least 48 months and then undergo a desensitization DBPCFC. Subjects will then be randomized to be off treatment for a period between 1 to 17 weeks. Subjects will then undergo a final DBPCFC.
Liquid peanut extract (Peanut SLIT): Liquid peanut extract will be administered under the tongue
|
Non-desensitized After Peanut SLIT
All subjects will receive peanut SLIT upon enrollment for at least 48 months and then undergo a desensitization DBPCFC. 'Non-desensitized' defined as experiencing dose limiting symptoms during the 5000mg desensitization DBPCFC.
|
|---|---|---|
|
Number of Participants With Gastrointestinal and Possible Gastrointestinal Eosinophilic Adverse Events.
Gastrointestinal adverse events
|
16 Participants
|
—
|
|
Number of Participants With Gastrointestinal and Possible Gastrointestinal Eosinophilic Adverse Events.
Possible eosinophilic gastrointestinal AEs
|
2 Participants
|
—
|
SECONDARY outcome
Timeframe: 48 monthsComparative estimates of changes in immune parameters (wheal size in mm during peanut skin prick test) from baseline through end of treatment among subjects who were induced with clinical desensitization (ingesting 5000mg on DBPCFC without symptoms) versus those who failed (developing clinical symptoms after ingesting 5000mg on DBPCFC).
Outcome measures
| Measure |
Peanut (Liquid Peanut Extract) SLIT
n=17 Participants
All subjects will receive peanut SLIT upon enrollment for at least 48 months and then undergo a desensitization DBPCFC. Subjects will then be randomized to be off treatment for a period between 1 to 17 weeks. Subjects will then undergo a final DBPCFC.
Liquid peanut extract (Peanut SLIT): Liquid peanut extract will be administered under the tongue
|
Non-desensitized After Peanut SLIT
n=37 Participants
All subjects will receive peanut SLIT upon enrollment for at least 48 months and then undergo a desensitization DBPCFC. 'Non-desensitized' defined as experiencing dose limiting symptoms during the 5000mg desensitization DBPCFC.
|
|---|---|---|
|
Change in Peanut Skin Test Wheal Over Time Among Subjects Who Were Induced With Clinical Desensitization Versus Those Who Failed
Baseline wheal size
|
14.5 mm
Interval 2.0 to 27.0
|
16.25 mm
Interval 5.5 to 36.5
|
|
Change in Peanut Skin Test Wheal Over Time Among Subjects Who Were Induced With Clinical Desensitization Versus Those Who Failed
48 month wheal size
|
7.25 mm
Interval 1.0 to 14.0
|
9.25 mm
Interval 2.0 to 25.5
|
SECONDARY outcome
Timeframe: 48 monthsComparative estimates of changes in immune parameters (serum levels of peanut specific IgE in kU/L) from baseline through end of treatment among subjects who were induced with clinical desensitization (ingesting 5000mg on DBPCFC without symptoms) versus those who failed (developing clinical symptoms after ingesting 5000mg on DBPCFC).
Outcome measures
| Measure |
Peanut (Liquid Peanut Extract) SLIT
n=17 Participants
All subjects will receive peanut SLIT upon enrollment for at least 48 months and then undergo a desensitization DBPCFC. Subjects will then be randomized to be off treatment for a period between 1 to 17 weeks. Subjects will then undergo a final DBPCFC.
Liquid peanut extract (Peanut SLIT): Liquid peanut extract will be administered under the tongue
|
Non-desensitized After Peanut SLIT
n=37 Participants
All subjects will receive peanut SLIT upon enrollment for at least 48 months and then undergo a desensitization DBPCFC. 'Non-desensitized' defined as experiencing dose limiting symptoms during the 5000mg desensitization DBPCFC.
|
|---|---|---|
|
Change in Peanut IgE Over Time Among Subjects Who Were Induced With Clinical Desensitization Versus Those Who Failed
Baseline peanut IgE
|
107 kU/L
Interval 0.3 to 1139.4
|
84.7 kU/L
Interval 10.9 to 1804.0
|
|
Change in Peanut IgE Over Time Among Subjects Who Were Induced With Clinical Desensitization Versus Those Who Failed
48 month peanut IgE
|
12.1 kU/L
Interval 0.05 to 484.0
|
11.2 kU/L
Interval 1.4 to 970.0
|
SECONDARY outcome
Timeframe: 48 monthsComparative estimates of changes in immune parameters (serum levels of peanut-specific IgG4 in mg/L) from baseline through end of treatment among subjects who were induced with clinical desensitization (ingesting 5000mg on DBPCFC without symptoms) versus those who failed (developing clinical symptoms after ingesting 5000mg on DBPCFC).
Outcome measures
| Measure |
Peanut (Liquid Peanut Extract) SLIT
n=17 Participants
All subjects will receive peanut SLIT upon enrollment for at least 48 months and then undergo a desensitization DBPCFC. Subjects will then be randomized to be off treatment for a period between 1 to 17 weeks. Subjects will then undergo a final DBPCFC.
Liquid peanut extract (Peanut SLIT): Liquid peanut extract will be administered under the tongue
|
Non-desensitized After Peanut SLIT
n=37 Participants
All subjects will receive peanut SLIT upon enrollment for at least 48 months and then undergo a desensitization DBPCFC. 'Non-desensitized' defined as experiencing dose limiting symptoms during the 5000mg desensitization DBPCFC.
|
|---|---|---|
|
Change in Peanut IgG4 Over Time Among Subjects Who Were Induced With Clinical Desensitization Versus Those Who Failed
Baseline peanut IgG4
|
0.47 mg/L
Interval 0.02 to 6.38
|
0.37 mg/L
Interval 0.02 to 19.65
|
|
Change in Peanut IgG4 Over Time Among Subjects Who Were Induced With Clinical Desensitization Versus Those Who Failed
48 month peanut IgG4
|
9.69 mg/L
Interval 0.04 to 80.0
|
4.39 mg/L
Interval 0.05 to 57.4
|
Adverse Events
Peanut (Liquid Peanut Extract) SLIT
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Peanut (Liquid Peanut Extract) SLIT
n=54 participants at risk
All subjects will receive peanut SLIT upon enrollment for at least 48 months and then undergo a desensitization DBPCFC. Subjects will then be randomized to be off treatment for a period between 1 to 17 weeks. Subjects will then undergo a final DBPCFC.
Liquid peanut extract (Peanut SLIT): Liquid peanut extract will be administered under the tongue
|
|---|---|
|
Gastrointestinal disorders
Vomiting
|
14.8%
8/54 • Adverse event data collected over 48 month peanut SLIT treatment period.
|
|
Gastrointestinal disorders
Diarrhea
|
5.6%
3/54 • Adverse event data collected over 48 month peanut SLIT treatment period.
|
|
Skin and subcutaneous tissue disorders
Rash
|
7.4%
4/54 • Adverse event data collected over 48 month peanut SLIT treatment period.
|
|
Respiratory, thoracic and mediastinal disorders
Runny nose
|
1.9%
1/54 • Adverse event data collected over 48 month peanut SLIT treatment period.
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
3.7%
2/54 • Adverse event data collected over 48 month peanut SLIT treatment period.
|
|
Skin and subcutaneous tissue disorders
Oropharyngeal itch
|
66.7%
36/54 • Adverse event data collected over 48 month peanut SLIT treatment period.
|
|
Respiratory, thoracic and mediastinal disorders
Sneezing
|
5.6%
3/54 • Adverse event data collected over 48 month peanut SLIT treatment period.
|
|
Respiratory, thoracic and mediastinal disorders
Coughing
|
5.6%
3/54 • Adverse event data collected over 48 month peanut SLIT treatment period.
|
|
Skin and subcutaneous tissue disorders
Itchy nose
|
1.9%
1/54 • Adverse event data collected over 48 month peanut SLIT treatment period.
|
|
Skin and subcutaneous tissue disorders
Skin itch
|
25.9%
14/54 • Adverse event data collected over 48 month peanut SLIT treatment period.
|
|
Skin and subcutaneous tissue disorders
Lip swelling
|
27.8%
15/54 • Adverse event data collected over 48 month peanut SLIT treatment period.
|
|
Skin and subcutaneous tissue disorders
Eye swelling
|
3.7%
2/54 • Adverse event data collected over 48 month peanut SLIT treatment period.
|
|
Skin and subcutaneous tissue disorders
Eye itch
|
3.7%
2/54 • Adverse event data collected over 48 month peanut SLIT treatment period.
|
|
Skin and subcutaneous tissue disorders
Eye tearing
|
3.7%
2/54 • Adverse event data collected over 48 month peanut SLIT treatment period.
|
|
Skin and subcutaneous tissue disorders
Hives
|
18.5%
10/54 • Adverse event data collected over 48 month peanut SLIT treatment period.
|
|
Gastrointestinal disorders
Belly pain
|
29.6%
16/54 • Adverse event data collected over 48 month peanut SLIT treatment period.
|
|
Skin and subcutaneous tissue disorders
Nasal congestion
|
1.9%
1/54 • Adverse event data collected over 48 month peanut SLIT treatment period.
|
Additional Information
Edwin Kim, MD; Director UNC Food Allergy Initiative
University of North Carolina at Chapel Hill
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place