Determining the Efficacy and Value of Immunotherapy on the Likelihood of Peanut Tolerance: The DEVIL Study

• Sponsor: University of North Carolina, Chapel Hill (Other)
• Overall Status: Completed
• CT.gov ID: NCT00932828
• Collaborator: (none)
• Enrollment: 37
• Location: 1
• Arm: 1
• Actual Duration (Months): 91.4
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

Peanut allergy is known to cause severe anaphylactic reactions.The goal of this proposal is to produce a new treatment that would benefit young subjects who have recently been diagnosed with peanut allergy by lowering the risk of anaphylactic reactions (desensitization), and changing the peanut-specific immune response in subjects who have peanut allergy (tolerance).

Condition or Disease	Intervention/Treatment	Phase
Food Hypersensitivity	Drug: Peanut oral immunotherapy	Phase 2

Detailed Description

Peanut allergy is known to cause severe anaphylactic reactions. Compared with other food allergies, it tends to be more persistent and its prevalence seems to be rising. Currently, there is no proven treatment other than strict avoidance. We are attempting to decrease the risk of anaphylaxis on accidental ingestion by desensitizing subjects to peanut using peanut mucosal immunotherapy (PMIT) more commonly called oral immunotherapy (OIT). We are also studying the effect of PMIT on the peanut-specific immune response to determine if tolerance to peanut protein will develop. Based on our preliminary work and recent studies supporting the importance of early oral exposure in tolerance induction, we propose that early treatment of peanut allergy with PMIT will be safe and effective. Children ages 9 to 36 months with peanut allergy will be randomized to receive high or low dose PMIT using peanut flour. Subjects will undergo desensitization on the first day and then increase the doses gradually to a maintenance dose. Doses will be taken daily at home except for dose increases which will be done on the research unit. Subjects will undergo a double-blinded, placebo-controlled food challenge (DBPCFC) if challenge criteria are met. Subjects passing the first challenge will stop PMIT and repeat the DBPCFC to assess tolerance. Outcome variables of interest include response to oral food challenges (OFC), skin prick testing, peanut specific serum immunoglobin E (IgE), immunoglobin G (IgG), and immunoglobin G4 (IgG4) and stool immunoglobin A (IgA), T and B cell responses, quality of life, and adverse events. As secondary and exploratory outcomes, these longitudinal results will be compared between high and low dose PMIT groups and controls using appropriate statistical analysis.

Study Design

• Study Type: Interventional
• Actual Enrollment: 37 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: For the purposes of the primary outcome, all subjects will receive peanut OIT and represent a single group. For exploratory analysis, subjects will be randomized to high and low dose OIT to potentially look for a dose response.For the purposes of the primary outcome, all subjects will receive peanut OIT and represent a single group. For exploratory analysis, subjects will be randomized to high and low dose OIT to potentially look for a dose response.
• Masking: None (Open Label)
• Masking Description: For exploratory analysis, subjects will be randomized 1:1 to high (3000mg) and low dose (300mg) OIT to potentially look for a dose response. Low dose will be masked by adding oat flour to provide a dose equal to high dose with respect to flour but with lower peanut protein content
• Primary Purpose: Treatment
• Official Title: Determining the Efficacy and Value of Immunotherapy on the Likelihood of Peanut Tolerance: The DEVIL Study; Grant "Optimizing Tolerance Induction in Peanut Allergy: The DEVIL Study"
• Actual Study Start Date: Jun 22, 2009
• Actual Primary Completion Date: Feb 1, 2017
• Actual Study Completion Date: Feb 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Peanut oral immunotherapy Newly diagnosed allergic children receiving peanut flour as oral immunotherapy for the treatment of peanut allergy.	Drug: Peanut oral immunotherapy; Defatted peanut in flour form to be used as treatment for peanut allergy; Other Names: Peanut mucosal immunotherapy Peanut OIT

Outcome Measures

Primary Outcome Measures

1. Determine the Percentage of Subjects Who Demonstrate Sustained Unresponsiveness (SU) by a Negative Double-blind Placebo-controlled Food Challenge (DBPCFC). [After 36 months of OIT dosing followed by 1 month of avoidance]

   The goal of the study is to treat peanut-allergic subjects with peanut OIT and to determine whether this protocol lowers their risk of anaphylactic reactions and causes SU. We expect to demonstrate the effectiveness of peanut OIT in inducing SU by showing that subjects will have a negative DBPCFC to 5 grams of peanut following completion of a 36-month course of peanut OIT followed by avoidance of therapy for 4 weeks.

Secondary Outcome Measures

1. Determine the Percentage of Subjects Who Demonstrate Desensitization by a Negative Double-blind Placebo-controlled Food Challenge (DBPCFC). [After 36 months of OIT dosing]

   We expect to demonstrate the effectiveness of peanut OIT in inducing desensitization by showing that subjects will have a negative DBPCFC to 5 grams of peanut following completion of a 36-month course of peanut OIT .

2. Determine the Frequency of Treatment-related Adverse Effects (TAE) From Peanut OIT. [After 36 months of OIT dosing followed by 1 month of avoidance]

   In addition to studying the effectiveness of peanut OIT, we will also determine the safety of peanut OIT by reporting the average rate of TAEs per person per dose.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 9 Months to 36 Months
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age 9-36 months of either sex, any race, any ethnicity at the time of the initial visit

• EITHER a positive skin prick test to peanuts or in vitro [CAP-FEIA] peanut immunoglobin E (IgE) level in the blood > 0.35 kU/L PLUS a history of a clinical allergic reaction (defined as significant clinical symptoms occurring within 60 minutes after ingesting peanuts) within 6 months of screening

• OR a positive prick skin test to peanuts and in vitro [CAP-FEIA] peanut IgE level > 5 kU/L when there is no history of allergic reaction and no known peanut exposure

• Provision of signed informed consent

• Development of symptoms characteristic of IgE-mediated food allergy (urticaria, angioedema, respiratory distress/wheeze/cough, vomiting/diarrhea, anaphylaxis) during initial oral food challenge

Exclusion Criteria:

• History of severe anaphylaxis to peanut as defined by hypoxia, hypotension, or neurological compromise

• Currently participating in a study using an investigational new drug

• Participation in any interventional study for the treatment of food allergy in the past 12 months

• Subjects with a known wheat food allergy will be excluded because of cross contamination of oat with wheat

• Severe atopic dermatitis

• Currently being treated with greater than medium daily doses of inhaled corticosteroids, as defined by the National Heart Lung and Blood Institute (NHLBI) guidelines

• Inability to discontinue antihistamines for skin testing and OFCs

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of North Carolina	Chapel Hill	North Carolina	United States	27599

Sponsors and Collaborators

• University of North Carolina, Chapel Hill

Investigators

• Principal Investigator: Arvil W Burks, MD, University of North Carolina

Study Documents (Full-Text)

• Study Protocol - Apr 8, 2013
• Statistical Analysis Plan - Apr 8, 2013

More Information

Publications

None provided.

• Responsible Party: University of North Carolina, Chapel Hill
• ClinicalTrials.gov Identifier: NCT00932828
• Other Study ID Numbers: 11-2307
• First Posted: Jul 3, 2009
• Last Update Posted: May 24, 2018
• Last Verified: Feb 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by University of North Carolina, Chapel Hill: Peanut allergy
• Additional relevant MeSH terms: Hypersensitivity; Food Hypersensitivity; Immunologic Factors

Study Results

Participant Flow

Arm/Group Title	Peanut Oral Immunotherapy
Arm/Group Description	All subjects are treated with peanut oral immunotherapy for primary outcome. Patients randomized to 300mg or 3000mg for secondary dose finding outcome.
Period Title: Overall Study
STARTED	37
COMPLETED	32
NOT COMPLETED	5

Baseline Characteristics

Arm/Group Title	Peanut Oral Immunotherapy
Arm/Group Description	All subjects who are treated with peanut OIT (300mg or 3000mg) and undergo a DBPCFC after 36 months of treatment and an additional DBPCFC after 4 weeks of treatment avoidance. Analysis was completed ITT.
Overall Participants	37
Age (Count of Participants)
<=18 years	37 100%
Between 18 and 65 years	0 0%
>=65 years	0 0%
Age (months) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [months]	28.5
Sex: Female, Male (Count of Participants)
Female	12 32.4%
Male	25 67.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 2.7%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	3 8.1%
White	33 89.2%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	37 100%
Peanut immunoglobin E (IgE) (kUA/L) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [kUA/L]	14.4
Peanut skin prick test (SPT) (mm wheal size) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [mm wheal size]	11.5

Outcome Measures

1. Primary Outcome

Title	Determine the Percentage of Subjects Who Demonstrate Sustained Unresponsiveness (SU) by a Negative Double-blind Placebo-controlled Food Challenge (DBPCFC).
Description	The goal of the study is to treat peanut-allergic subjects with peanut OIT and to determine whether this protocol lowers their risk of anaphylactic reactions and causes SU. We expect to demonstrate the effectiveness of peanut OIT in inducing SU by showing that subjects will have a negative DBPCFC to 5 grams of peanut following completion of a 36-month course of peanut OIT followed by avoidance of therapy for 4 weeks.
Time Frame	After 36 months of OIT dosing followed by 1 month of avoidance

Outcome Measure Data

Analysis Population Description

37 subjects considered with ITT analysis including 5 withdrawals

Arm/Group Title	Peanut Oral Immunotherapy
Arm/Group Description	All subjects who are treated with peanut OIT (300mg or 3000mg) and undergo a DBPCFC after 36 months of treatment and an additional DBPCFC after 4 weeks of treatment avoidance. Analysis was completed as ITT.
Measure Participants	37
Count of Participants [Participants]	29 78.4%

2. Secondary Outcome

Title	Determine the Percentage of Subjects Who Demonstrate Desensitization by a Negative Double-blind Placebo-controlled Food Challenge (DBPCFC).
Description	We expect to demonstrate the effectiveness of peanut OIT in inducing desensitization by showing that subjects will have a negative DBPCFC to 5 grams of peanut following completion of a 36-month course of peanut OIT .
Time Frame	After 36 months of OIT dosing

Outcome Measure Data

Analysis Population Description

37 subjects considered with ITT analysis including 5 withdrawals

Arm/Group Title	Peanut Oral Immunotherapy
Arm/Group Description	All subjects who are treated with peanut OIT (300mg or 3000mg) and undergo a DBPCFC after 36 months of treatment and an additional DBPCFC after 4 weeks of treatment avoidance. Analysis was completed as ITT.
Measure Participants	37
Count of Participants [Participants]	30 81.1%

3. Secondary Outcome

Title	Determine the Frequency of Treatment-related Adverse Effects (TAE) From Peanut OIT.
Description	In addition to studying the effectiveness of peanut OIT, we will also determine the safety of peanut OIT by reporting the average rate of TAEs per person per dose.
Time Frame	After 36 months of OIT dosing followed by 1 month of avoidance

Outcome Measure Data

Analysis Population Description

37 subjects considered with ITT analysis including 5 withdrawals

Arm/Group Title	Peanut Oral Immunotherapy
Arm/Group Description	All subjects who are treated with peanut OIT (300mg or 3000mg) and undergo a DBPCFC after 36 months of treatment and an additional DBPCFC after 4 weeks of treatment avoidance. Analysis was completed as ITT.
Measure Participants	37
Median (95% Confidence Interval) [AEs per person per dose]	0.8

Adverse Events

Time Frame	TAEs reported over the course of 36 months of peanut OIT treatment for each subject
Arm/Group Title	Peanut Oral Immunotherapy
Arm/Group Description	All subjects who are treated with peanut OIT (300mg or 3000mg) and undergo a DBPCFC after 36 months of treatment and an additional DBPCFC after 4 weeks of treatment avoidance. Analysis was completed as ITT.
All Cause Mortality
	Peanut Oral Immunotherapy
	Affected / at Risk (%)	# Events
Total	0/37 (0%)
Serious Adverse Events
	Peanut Oral Immunotherapy
	Affected / at Risk (%)	# Events
Total	0/37 (0%)
Other (Not Including Serious) Adverse Events
	Peanut Oral Immunotherapy
	Affected / at Risk (%)	# Events
Total	35/37 (94.6%)
Gastrointestinal disorders
Abdominal pain	22/37 (59.5%)
Nausea/vomiting	23/37 (62.2%)
General disorders
Multiple symptoms	11/37 (29.7%)
Respiratory, thoracic and mediastinal disorders
Sneezing/congestion	13/37 (35.1%)
Skin and subcutaneous tissue disorders
Skin/oral pruritus	19/37 (51.4%)
Hives	20/37 (54.1%)
Rash (not hives)	29/37 (78.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.