Sublingual Immunotherapy for Peanut Allergy and Induction of Tolerance (SLIT-TLC)

• ClinicalTrials.gov Identifier: NCT01373242
• Recruitment Status: Completed
• First Posted: June 14, 2011
• Results First Posted: June 12, 2019
• Last Update Posted: June 12, 2019
• Sponsor: University of North Carolina, Chapel Hill
• Collaborator: National Center for Complementary and Integrative Health (NCCIH)
• Information provided by (Responsible Party): University of North Carolina, Chapel Hill

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Peanut Hypersensitivity; Food Hypersensitivity; Food Allergy; Peanut Allergy
• Intervention: Drug: Liquid peanut extract (Peanut SLIT)
• Enrollment: 54

Participant Flow

Recruitment Details	Peanut allergic children ages 1-11 years
Pre-assignment Details

Arm/Group Title	Peanut (Liquid Peanut Extract) SLIT
Arm/Group Description	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
Period Title: Overall Study
Started	54
Completed	38
Not Completed	16

Baseline Characteristics

Arm/Group Title		Peanut ( Liquid Peanut Extract) SLIT
Arm/Group Description		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
Overall Number of Baseline Participants		54
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	54 participants
	<=18 years	54 100.0%
	Between 18 and 65 years	0 0.0%
	>=65 years	0 0.0%
Age, Continuous [1]; Median (Full Range); Unit of measure: Years
	Number Analyzed	54 participants
		7.05; (2.3 to 11.9)
		[1] Measure Description: Inclusion criteria: age 1 year up to but not including 12 years.
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	54 participants
	Female	20 37.0%
	Male	34 63.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	54 participants
	American Indian or Alaska Native	0 0.0%
	Asian	4 7.4%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	0 0.0%
	White	49 90.7%
	More than one race	1 1.9%
	Unknown or Not Reported	0 0.0%
Region of Enrollment; Measure Type: Count of Participants; Unit of measure: Participants
United States	Number Analyzed	54 participants
		54 100.0%
Peanut-specific IgE (kU/L); Median (Full Range); Unit of measure: kU/L
	Number Analyzed	54 participants
		85.6; (0.3 to 1804)
Peanut skin prick test wheal size (mm); Median (Full Range); Unit of measure: Mm
	Number Analyzed	54 participants
		16; (2 to 36.5)

Outcome Measures

1. Primary Outcome

Title	Population Sensitization Threshold in mg Peanut Protein Predicted to Provoke Reactions in 5% of the Peanut-allergic Population
Description	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.
Time Frame	48 - 52 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Peanut (Liquid Peanut Extract) SLIT
Arm/Group Description:	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 Number of Participants Analyzed	54
Measure Type: Number; Unit of Measure: mg
NOAEL threshold	160
LOAEL threshold	300

2. Primary Outcome

Title	Population Sensitization Threshold in mg Peanut Protein Predicted to Provoke Reactions in 10% of the Peanut-allergic Population
Description	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 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.
Time Frame	48-52 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Peanut (Liquid Peanut Extract) SLIT
Arm/Group Description:	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 Number of Participants Analyzed	54
Measure Type: Number; Unit of Measure: mg
NOAEL threshold	800
LOAEL threshold	750

3. Primary Outcome

Title	Population Estimate of Time for a Subject's True Sensitivity Threshold to Reduce by Half.
Description	A 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.
Time Frame	52 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Peanut (Liquid Peanut Extract) SLIT
Arm/Group Description:	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 Number of Participants Analyzed	54
Measure Type: Number; Unit of Measure: weeks
	17

4. Primary Outcome

Title	Population Estimate of a Subject's True Sensitivity Threshold to Maintain at the Same Dose Level During DBPCFC
Description	A 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.
Time Frame	52 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Peanut (Liquid Peanut Extract) SLIT
Arm/Group Description:	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 Number of Participants Analyzed	54
Measure Type: Number; Unit of Measure: weeks
	13

5. Primary Outcome

Title	Population Estimate of a Subject's True Sensitivity Threshold to Decrease by One Dose Level of During the DBPCFC
Description	A 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.
Time Frame	52 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Peanut (Liquid Peanut Extract) SLIT
Arm/Group Description:	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 Number of Participants Analyzed	54
Measure Type: Number; Unit of Measure: weeks
	14

6. Secondary Outcome

Title	Number of Participants With Adverse Events and Serious Adverse Events During the Study.
Description	Number of participants with adverse events (AEs) and serious adverse events (SAEs) during the SLIT treatment portion of the study.
Time Frame	48 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Peanut (Liquid Peanut Extract) SLIT
Arm/Group Description:	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 Number of Participants Analyzed	54
Measure Type: Count of Participants; Unit of Measure: Participants
Adverse events	53 98.1%
Serious adverse events	0 0.0%

7. Secondary Outcome

Title	Number of Participants With Gastrointestinal and Possible Gastrointestinal Eosinophilic Adverse Events.
Description	With 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
Time Frame	48 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Peanut (Liquid Peanut Extract) SLIT
Arm/Group Description:	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 Number of Participants Analyzed	54
Measure Type: Count of Participants; Unit of Measure: Participants
Gastrointestinal adverse events	16 29.6%
Possible eosinophilic gastrointestinal AEs	2 3.7%

8. Secondary Outcome

Title	Change in Peanut Skin Test Wheal Over Time Among Subjects Who Were Induced With Clinical Desensitization Versus Those Who Failed
Description	Comparative 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).
Time Frame	48 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Desensitized After Peanut SLIT	Non-desensitized After Peanut SLIT
Arm/Group Description:	All subjects will receive peanut SLIT upon enrollment for at least 48 months and then undergo a desensitization DBPCFC. 'Desensitized' defined as completing the 5000mg desensitization DBPCFC without dose limiting symptoms.	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.
Overall Number of Participants Analyzed	17	37
Median (Full Range); Unit of Measure: mm
Baseline wheal size	14.5; (2 to 27)	16.25; (5.5 to 36.5)
48 month wheal size	7.25; (1 to 14)	9.25; (2 to 25.5)

9. Secondary Outcome

Title	Change in Peanut IgE Over Time Among Subjects Who Were Induced With Clinical Desensitization Versus Those Who Failed
Description	Comparative 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).
Time Frame	48 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Desensitized After Peanut SLIT	Non-desensitized After Peanut SLIT
Arm/Group Description:	All subjects will receive peanut SLIT upon enrollment for at least 48 months and then undergo a desensitization DBPCFC. 'Desensitized' defined as completing the 5000mg desensitization DBPCFC without dose limiting symptoms.	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.
Overall Number of Participants Analyzed	17	37
Median (Full Range); Unit of Measure: kU/L
Baseline peanut IgE	107; (0.3 to 1139.4)	84.7; (10.9 to 1804)
48 month peanut IgE	12.1; (0.05 to 484)	11.2; (1.4 to 970)

10. Secondary Outcome

Title	Change in Peanut IgG4 Over Time Among Subjects Who Were Induced With Clinical Desensitization Versus Those Who Failed
Description	Comparative 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).
Time Frame	48 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Desensitized After Peanut SLIT	Non-desensitized After Peanut SLIT
Arm/Group Description:	All subjects will receive peanut SLIT upon enrollment for at least 48 months and then undergo a desensitization DBPCFC. 'Desensitized' defined as completing the 5000mg desensitization DBPCFC without dose limiting symptoms.	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.
Overall Number of Participants Analyzed	17	37
Median (Full Range); Unit of Measure: mg/L
Baseline peanut IgG4	0.47; (0.02 to 6.38)	0.37; (0.02 to 19.65)
48 month peanut IgG4	9.69; (0.04 to 80)	4.39; (0.05 to 57.4)

Adverse Events

Time Frame	Adverse event data collected over 48 month peanut SLIT treatment period.
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Peanut (Liquid Peanut Extract) SLIT
Arm/Group Description	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
All-Cause Mortality
	Peanut (Liquid Peanut Extract) SLIT
	Affected / at Risk (%)
Total	0/54 (0.00%)
Serious Adverse Events
	Peanut (Liquid Peanut Extract) SLIT
	Affected / at Risk (%)
Total	0/54 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Peanut (Liquid Peanut Extract) SLIT
	Affected / at Risk (%)
Total	53/54 (98.15%)
Gastrointestinal disorders
Vomiting †	8/54 (14.81%)
Diarrhea †	3/54 (5.56%)
Belly pain †	16/54 (29.63%)
Respiratory, thoracic and mediastinal disorders
Runny nose †	1/54 (1.85%)
Wheezing †	2/54 (3.70%)
Sneezing †	3/54 (5.56%)
Coughing †	3/54 (5.56%)
Skin and subcutaneous tissue disorders
Rash †	4/54 (7.41%)
Oropharyngeal itch †	36/54 (66.67%)
Itchy nose †	1/54 (1.85%)
Skin itch †	14/54 (25.93%)
Lip swelling †	15/54 (27.78%)
Eye swelling †	2/54 (3.70%)
Eye itch †	2/54 (3.70%)
Eye tearing †	2/54 (3.70%)
Hives †	10/54 (18.52%)
Nasal congestion †	1/54 (1.85%)
† Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Edwin Kim, MD; Director UNC Food Allergy Initiative
• Organization: University of North Carolina at Chapel Hill
• Phone: 919-537-3193
• EMail: edwinkim@email.unc.edu

• Responsible Party: University of North Carolina, Chapel Hill
• ClinicalTrials.gov Identifier: NCT01373242
• Other Study ID Numbers: 11-2308; 5R01AT004435-09 ( U.S. NIH Grant/Contract )
• First Submitted: June 12, 2011
• First Posted: June 14, 2011
• Results First Submitted: April 11, 2019
• Results First Posted: June 12, 2019
• Last Update Posted: June 12, 2019