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Oral Immunotherapy for Childhood Egg Allergy

Primary Purpose

Hypersensitivity, Immediate Hypersensitivity, Food Hypersensitivity

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Egg oral immunotherapy
Control Group
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hypersensitivity focused on measuring Egg Allergy, Egg Oral Immunotherapy (OIT), Food Allergy

Eligibility Criteria

5 Years - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Convincing clinical history of egg allergy
  • Age 6 to 18 years, with a serum IgE [UniCAP] to egg > 5 kUA/L OR
  • Age 5 to 6 years, with a serum IgE [UniCAP] to egg ≥ 12kUA/L
  • Parent/guardian willing to provide informed consent
  • Willing to use acceptable forms of contraception

Exclusion Criteria:

  • History of severe anaphylaxis to egg. More information on this criterion can be found in the protocol.
  • Known allergy to corn
  • Chronic disease requiring therapy (e.g., heart disease, diabetes). Participants who have asthma, atopic dermatitis, or rhinitis are not excluded.
  • Participation in any interventional study for the treatment of food allergy in the 6 months prior to study entry
  • Participant is on "build-up phase" of immunotherapy and has not reached maintenance dosing. Participants tolerating maintenance allergen immunotherapy are not excluded.
  • Severe asthma, uncontrolled mild or moderate asthma. More information on this criterion can be found in the protocol.
  • Inability to discontinue antihistamines for the initial day of escalation, skin testing, and OFC
  • Omalizumab or other nontraditional forms of oral or sublingual allergen immunotherapy, immunomodulator therapy, or biologic therapy in the 12 months prior to study entry. Participants who have taken corticosteroids are not excluded.
  • Investigational drugs 90 days prior to study entry or planned use of an investigational drug during the study period
  • Pregnancy or breastfeeding

Sites / Locations

  • University of Arkansas Children's Hospital Research Institute
  • National Jewish Medical and Research Center
  • Johns Hopkins University School of Medicine
  • Mount Sinai School of Medicine
  • University of North Carolina

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Egg Oral Immunotherapy (OIT)

Control Group

Arm Description

Subjects ingest egg white solid (EWS) on Visit 1 (initial day dose escalation up to 50 mg), followed by a build-up phase (escalating daily egg doses every 2 wks, achieving a maintenance dose by 32-40 wks). Thereafter, subjects are on a maximally tolerated daily egg dose (306 mg to 2 gm) for ≥8 wks. After wk 44, subjects are given a 5 gm Oral Food Challenge (OFC) using EWS to identify desensitized [1] subjects. Subjects/study staff are unblinded following this OFC and either continue on their egg OIT maintenance dose of 2 gm/day or are allowed to attempt escalation up to 2 gm/day for the remainder of the study (1-3 years). A 10 gm OFC to identify desensitized [1] subjects occurs at specified intervals under prescribed conditions (yrs 2 - 4). Subjects who pass this 1st 10 gm OFC stop study therapy for 4-6 wks, then have a 2nd 10 gm OFC. Subjects that pass this 2nd 10 gm OFC are considered tolerant [2], stop EWS dosing and add egg to their diet.

Subjects ingest placebo (cornstarch) during Visit 1 (initial day of dose escalation up to 50 mg), followed by a build-up phase (escalating daily placebo doses every 2 wks, achieving a maintenance dose by 32-40 wks). Thereafter, subjects were on a maximally tolerated daily placebo dose (306 mg to 2 gm) for ≥8 wks. After wk 44, subjects were given a 5 gm Oral Food Challenge (OFC) using egg white solid to identify desensitized [1] subjects. Subjects/study staff were unblinded following this initial 5 gm OFC. After unblinding, subjects discontinued further placebo dosing and continued on an egg-restricted diet. A 10 gm OFC was administered under prescribed conditions to subjects if their egg-specific serum IgE level was below 2 kUA/L. They were followed in the study up to 2 years. [1] Desensitized: Subject does not react to egg during OFC while taking daily doses of therapy. [2] Tolerant: Subject does not react to egg during OFC 4-6 wks after abstinence from egg consumption.

Outcomes

Primary Outcome Measures

Percent of Participants Who Successfully Consumed 10,000 mg of Egg White Solid Followed by Open Feeding of Egg
Tolerance Assessment: Participants who successfully consumed without dose-limiting symptoms 10,000 mg of egg white solid during a double-blind placebo-controlled oral food challenge were then given an open feeding of egg and those who successfully consumed the open feeding of egg were counted as successes.

Secondary Outcome Measures

Percent of Participants Who Successfully Consumed 5,000 mg of Egg White Solid
Desensitization assessment: Participants who successfully consumed without dose-limiting symptoms 5,000 mg of egg white solid during a double-blind placebo-controlled oral food challenge were counted as successes.
Percent of Participants Who Successfully Consumed a 50 mg Dose at Initial Escalation
On the initial day of dosing, participants were offered 0.1 mg of egg white solid or placebo followed by an approximate doubling every 30 minutes up to a 50 mg dose providing limiting reactions do not occur.
Percent of Participants Who Achieved a Maintenance Dose of 2,000 mg
For participants whose maximum tolerated dose on the initial escalation day was less than 50 mg, doses were doubled every 2 weeks up to 50 mg. After 50 mg, dosing was increased to 75 mg, and then dosing increased by 25% until the 2000 mg dose was reached. The maximum time allowed for the build-up phase was 40 weeks; the dose achieved at 40 weeks was considered the maintenance dose.
Number of Participants With Serious Adverse Events (SAEs)
This study graded the severity of Adverse Events experienced by participants according to the criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.
Percent of Participants in the Egg OIT Treatment Arm Who Successfully Consumed 10,000 mg of Egg White Solid
Tolerance Assessment: Participants in the Egg OIT treatment arm who were not tolerant at 2 years were offered an additional 2 years of therapy. A 10,000 mg double-blind placebo controlled oral food challenge to egg was done the same way as the one performed at 2 years for these participants in order to identify tolerant individuals in the 2 to 4 year extension segment. The tolerant individuals from this segment were then added to the tolerant individuals from the 2 year segment.

Full Information

First Posted
April 16, 2007
Last Updated
November 15, 2017
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Consortium of Food Allergy Research
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1. Study Identification

Unique Protocol Identification Number
NCT00461097
Brief Title
Oral Immunotherapy for Childhood Egg Allergy
Official Title
Oral Desensitization to Egg With Subsequent Induction of Tolerance for Egg-Allergic Children (CoFAR 3)
Study Type
Interventional

2. Study Status

Record Verification Date
November 2017
Overall Recruitment Status
Completed
Study Start Date
May 2007 (undefined)
Primary Completion Date
December 2010 (Actual)
Study Completion Date
December 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Consortium of Food Allergy Research

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to determine if oral immunotherapy (OIT) will desensitize a child with an allergy to egg and eventually lead to the development of tolerance to egg.
Detailed Description
In the United States, as many as 6% to 8% of children are affected by food allergy. In young children, allergic reactions to egg can range from mild rash to systemic anaphylaxis. The usual standard of care for allergy is complete avoidance of this food allergen and treatment of accidental systemic reactions by access to self-injected epinephrine. However, accidental exposure to allergens in processed foods may be difficult to avoid. Currently, several therapeutic strategies are being investigated to prevent and treat food allergies. Since standard injection (under the skin) immunotherapy for food allergy is associated with a high rate of allergic reactions, a few studies have recently tried oral immunotherapy (OIT) in food allergy. The purpose of this study is to determine the safety and efficacy of the administration of OIT. The intent is to develop desensitization and eventually tolerance to egg allergen. This study will evaluate tolerance to egg white solid that may be gained by gradually increasing the amounts of egg white solid given to a child over a long period of time. This study will last up to 48 months. The participants will be randomly assigned to receive oral immunotherapy treatment with egg white solid or placebo. This study will include dose escalation and maintenance followed by oral food challenge (OFC). For participants receiving egg OIT, visit 1 consists of multiple small incremental doses of egg white solid. This is followed by 32-40 weeks of gradual dose escalation to a stable maintenance dose of egg white solid for at least 8 weeks. At approximately Week 44, participants are given an OFC using 5 grams of egg white solid to identify desensitized individuals. Participants and study staff are unblinded following this initial OFC. Maintenance egg OIT therapy is continued for an additional 1-3 years. Oral Food Challenges with 10 grams of egg white solid will be performed for participants on maintenance egg OIT at subsequent time points (approximately Week 96 and annually thereafter) to test for desensitization. If passed, a repeat OFC after being off therapy for 4-6 weeks will be performed to test for tolerance. An OFC to test for tolerance will use 10 grams of egg white solid and be followed by an open feeding of egg. Participants receiving placebo during dose escalation and maintenance are given an OFC using 5 grams of egg white solid to test for desensitization at approximately 44 weeks. They are unblinded at that time, continue on an egg-restricted diet, and are followed until up to 2 years. These participants will only receive an OFC at a subsequent time point if their egg Immunoglobulin E (IgE) declines to be less than 2 kilounits of antibody per liter; this OFC will use 10 grams of egg white solid and be followed by an open feeding of egg. At selected visits, blood and urine collection, physical examination, prick skin tests, and atopic dermatitis and asthma evaluations will occur.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypersensitivity, Immediate Hypersensitivity, Food Hypersensitivity
Keywords
Egg Allergy, Egg Oral Immunotherapy (OIT), Food Allergy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
55 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Egg Oral Immunotherapy (OIT)
Arm Type
Experimental
Arm Description
Subjects ingest egg white solid (EWS) on Visit 1 (initial day dose escalation up to 50 mg), followed by a build-up phase (escalating daily egg doses every 2 wks, achieving a maintenance dose by 32-40 wks). Thereafter, subjects are on a maximally tolerated daily egg dose (306 mg to 2 gm) for ≥8 wks. After wk 44, subjects are given a 5 gm Oral Food Challenge (OFC) using EWS to identify desensitized [1] subjects. Subjects/study staff are unblinded following this OFC and either continue on their egg OIT maintenance dose of 2 gm/day or are allowed to attempt escalation up to 2 gm/day for the remainder of the study (1-3 years). A 10 gm OFC to identify desensitized [1] subjects occurs at specified intervals under prescribed conditions (yrs 2 - 4). Subjects who pass this 1st 10 gm OFC stop study therapy for 4-6 wks, then have a 2nd 10 gm OFC. Subjects that pass this 2nd 10 gm OFC are considered tolerant [2], stop EWS dosing and add egg to their diet.
Arm Title
Control Group
Arm Type
Placebo Comparator
Arm Description
Subjects ingest placebo (cornstarch) during Visit 1 (initial day of dose escalation up to 50 mg), followed by a build-up phase (escalating daily placebo doses every 2 wks, achieving a maintenance dose by 32-40 wks). Thereafter, subjects were on a maximally tolerated daily placebo dose (306 mg to 2 gm) for ≥8 wks. After wk 44, subjects were given a 5 gm Oral Food Challenge (OFC) using egg white solid to identify desensitized [1] subjects. Subjects/study staff were unblinded following this initial 5 gm OFC. After unblinding, subjects discontinued further placebo dosing and continued on an egg-restricted diet. A 10 gm OFC was administered under prescribed conditions to subjects if their egg-specific serum IgE level was below 2 kUA/L. They were followed in the study up to 2 years. [1] Desensitized: Subject does not react to egg during OFC while taking daily doses of therapy. [2] Tolerant: Subject does not react to egg during OFC 4-6 wks after abstinence from egg consumption.
Intervention Type
Drug
Intervention Name(s)
Egg oral immunotherapy
Intervention Description
Egg white solid powder
Intervention Type
Drug
Intervention Name(s)
Control Group
Intervention Description
Placebo for egg white solid
Primary Outcome Measure Information:
Title
Percent of Participants Who Successfully Consumed 10,000 mg of Egg White Solid Followed by Open Feeding of Egg
Description
Tolerance Assessment: Participants who successfully consumed without dose-limiting symptoms 10,000 mg of egg white solid during a double-blind placebo-controlled oral food challenge were then given an open feeding of egg and those who successfully consumed the open feeding of egg were counted as successes.
Time Frame
At the 2 year time point; Egg OIT participants must be approximately 4-6 weeks post-discontinuation of therapy
Secondary Outcome Measure Information:
Title
Percent of Participants Who Successfully Consumed 5,000 mg of Egg White Solid
Description
Desensitization assessment: Participants who successfully consumed without dose-limiting symptoms 5,000 mg of egg white solid during a double-blind placebo-controlled oral food challenge were counted as successes.
Time Frame
Following the blinded desensitization phase at approximately Week 44
Title
Percent of Participants Who Successfully Consumed a 50 mg Dose at Initial Escalation
Description
On the initial day of dosing, participants were offered 0.1 mg of egg white solid or placebo followed by an approximate doubling every 30 minutes up to a 50 mg dose providing limiting reactions do not occur.
Time Frame
Initial day of dosing
Title
Percent of Participants Who Achieved a Maintenance Dose of 2,000 mg
Description
For participants whose maximum tolerated dose on the initial escalation day was less than 50 mg, doses were doubled every 2 weeks up to 50 mg. After 50 mg, dosing was increased to 75 mg, and then dosing increased by 25% until the 2000 mg dose was reached. The maximum time allowed for the build-up phase was 40 weeks; the dose achieved at 40 weeks was considered the maintenance dose.
Time Frame
Following the blinded desensitization phase at approximately Week 44
Title
Number of Participants With Serious Adverse Events (SAEs)
Description
This study graded the severity of Adverse Events experienced by participants according to the criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.
Time Frame
Baseline through the 2-year primary endpoint
Title
Percent of Participants in the Egg OIT Treatment Arm Who Successfully Consumed 10,000 mg of Egg White Solid
Description
Tolerance Assessment: Participants in the Egg OIT treatment arm who were not tolerant at 2 years were offered an additional 2 years of therapy. A 10,000 mg double-blind placebo controlled oral food challenge to egg was done the same way as the one performed at 2 years for these participants in order to identify tolerant individuals in the 2 to 4 year extension segment. The tolerant individuals from this segment were then added to the tolerant individuals from the 2 year segment.
Time Frame
4 years (48 months)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
5 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Convincing clinical history of egg allergy Age 6 to 18 years, with a serum IgE [UniCAP] to egg > 5 kUA/L OR Age 5 to 6 years, with a serum IgE [UniCAP] to egg ≥ 12kUA/L Parent/guardian willing to provide informed consent Willing to use acceptable forms of contraception Exclusion Criteria: History of severe anaphylaxis to egg. More information on this criterion can be found in the protocol. Known allergy to corn Chronic disease requiring therapy (e.g., heart disease, diabetes). Participants who have asthma, atopic dermatitis, or rhinitis are not excluded. Participation in any interventional study for the treatment of food allergy in the 6 months prior to study entry Participant is on "build-up phase" of immunotherapy and has not reached maintenance dosing. Participants tolerating maintenance allergen immunotherapy are not excluded. Severe asthma, uncontrolled mild or moderate asthma. More information on this criterion can be found in the protocol. Inability to discontinue antihistamines for the initial day of escalation, skin testing, and OFC Omalizumab or other nontraditional forms of oral or sublingual allergen immunotherapy, immunomodulator therapy, or biologic therapy in the 12 months prior to study entry. Participants who have taken corticosteroids are not excluded. Investigational drugs 90 days prior to study entry or planned use of an investigational drug during the study period Pregnancy or breastfeeding
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wesley Burks, MD
Organizational Affiliation
University of North Carolina
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Stacie Jones, MD
Organizational Affiliation
Allergy/Immunology Department, Arkansas Children's Hospital
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Robert Wood, MD
Organizational Affiliation
Johns Hopkins University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Scott Sicherer, MD
Organizational Affiliation
Icahn School of Medicine at Mount Sinai
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
David Fleischer, MD
Organizational Affiliation
National Jewish Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Arkansas Children's Hospital Research Institute
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72202
Country
United States
Facility Name
National Jewish Medical and Research Center
City
Denver
State/Province
Colorado
ZIP/Postal Code
80206
Country
United States
Facility Name
Johns Hopkins University School of Medicine
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21205
Country
United States
Facility Name
Mount Sinai School of Medicine
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
University of North Carolina
City
Chapel Hills
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Participant level data and additional relevant materials are available to the public in the Immunology Database and Analysis Portal (ImmPort). ImmPort is a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts.
Citations:
PubMed Identifier
16272231
Citation
Baral VR, Hourihane JO. Food allergy in children. Postgrad Med J. 2005 Nov;81(961):693-701. doi: 10.1136/pgmj.2004.030288.
Results Reference
background
PubMed Identifier
16455349
Citation
Sicherer SH, Sampson HA. 9. Food allergy. J Allergy Clin Immunol. 2006 Feb;117(2 Suppl Mini-Primer):S470-5. doi: 10.1016/j.jaci.2005.05.048.
Results Reference
background
PubMed Identifier
12777603
Citation
Wood RA. The natural history of food allergy. Pediatrics. 2003 Jun;111(6 Pt 3):1631-7.
Results Reference
background
PubMed Identifier
22808958
Citation
Burks AW, Jones SM, Wood RA, Fleischer DM, Sicherer SH, Lindblad RW, Stablein D, Henning AK, Vickery BP, Liu AH, Scurlock AM, Shreffler WG, Plaut M, Sampson HA; Consortium of Food Allergy Research (CoFAR). Oral immunotherapy for treatment of egg allergy in children. N Engl J Med. 2012 Jul 19;367(3):233-43. doi: 10.1056/NEJMoa1200435.
Results Reference
result
PubMed Identifier
26924470
Citation
Jones SM, Burks AW, Keet C, Vickery BP, Scurlock AM, Wood RA, Liu AH, Sicherer SH, Henning AK, Lindblad RW, Dawson P, Berin C, Fleischer DM, Leung DYM, Plaut M, Sampson HA; Consortium of Food Allergy Research (CoFAR). Long-term treatment with egg oral immunotherapy enhances sustained unresponsiveness that persists after cessation of therapy. J Allergy Clin Immunol. 2016 Apr;137(4):1117-1127.e10. doi: 10.1016/j.jaci.2015.12.1316. Epub 2016 Mar 9.
Results Reference
derived
Available IPD and Supporting Information:
Available IPD/Information Type
Individual Participant Data Set
Available IPD/Information URL
http://www.immport.org/immport-open/public/study/study/displayStudyDetail/SDY218
Available IPD/Information Identifier
SDY218
Available IPD/Information Comments
ImmPort study identifier is SDY218
Available IPD/Information Type
Study summary, -design, -adverse events, -demographics,-lab tests,-mechanistic assays, -study files
Available IPD/Information URL
http://www.immport.org/immport-open/public/study/study/displayStudyDetail/SDY218
Available IPD/Information Identifier
SDY218
Available IPD/Information Comments
ImmPort study identifier is SDY218

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Oral Immunotherapy for Childhood Egg Allergy

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