MAP-X: Study Using Xolair in Rush Multi Oral Immunotherapy in Multi Food Allergic Patients

• Sponsor: Stanford University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02643862
• Collaborator: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Enrollment: 48
• Location: 1
• Arms: 2
• Actual Duration (Months): 17.1
• Patients Per Site Per Month: 2.8

Study Details

Study Description

Brief Summary

This is a pilot randomized, double-blind, placebo controlled study which will be conducted at a single center. All participants will receive oral immunotherapy for their specific food allergies (limited to 5 of those food allergens in IND 14831). In a 3:1 ratio, 36* participants will receive Xolair for 16 weeks while 12* will receive corresponding placebo instead of Xolair. 12 controls will be enrolled who will receive no OIT and no Xolair. These 12 controls are not part of the randomization. The total number of participants randomized to the two arms is 48*.

Condition or Disease	Intervention/Treatment	Phase
Food Allergy	Drug: Xolair; Drug: Placebo	Phase 1/Phase 2

Detailed Description

We will enroll multi food allergic participants (4-55 years of age) with proven "multi food allergies". We anticipate enrolling 60 participants with allergies to, at least two foods. Participants must have food specific IgE>4kU/L for each allergen or a skin test reactivity to each food allergen ≥ 6 mm wheal diameter. We have chosen criteria associated with a very low likelihood of natural loss of food allergy for the duration of this protocol. These values of specific IgE and SPT were chosen based on the opinions of 4 experts. Participants also must have a total IgE <1500kU/L, a clinical reaction during a double blind placebo controlled food challenge (DBPCFC) with food proteins/powders to establish sensitivity to given food proteins/powders (milk, egg, peanut, almond, wheat, cashew, sesame seed, soy, walnut, hazelnut) and no clinical reaction during placebo (oat) as per CMC section of IND.

Participants will undergo a rush desensitization day at week 8 to a maximum dose of 1,250 mg total protein. Participants will be ingesting either 2 to 5 food allergens, depending on their allergy screening. They will consume home doses for two weeks based on the these results and document reactions. Upon returning to the CFRU (Clinical Food Research Unit) two weeks later, a dose escalation will be attempted. This cycle will continue until the participant reaches a maximum dose of 2,000 mg protein daily of each food allergen (two to five food allergens to be ingested by the participant). No more than 5 allergens will be given.

Study Design

• Study Type: Interventional
• Actual Enrollment: 48 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: In a 3:1 ratio, 36* participants will receive Xolair for 16 weeks while 12* will receive corresponding placebo instead of Xolair. 12 controls will be enrolled who will receive no OIT and no Xolair. These 12 controls are not part of the randomization. The total number of participants randomized to the two arms is 48*.In a 3:1 ratio, 36* participants will receive Xolair for 16 weeks while 12* will receive corresponding placebo instead of Xolair. 12 controls will be enrolled who will receive no OIT and no Xolair. These 12 controls are not part of the randomization. The total number of participants randomized to the two arms is 48*.
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Randomized, Controlled, Blinded, Pilot Study Using Xolair in Rush Multi Oral Immunotherapy in Multi Food Allergic Patients
• Actual Study Start Date: Mar 18, 2015
• Actual Primary Completion Date: Aug 20, 2016
• Actual Study Completion Date: Aug 20, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: xolair Pts will be randomized to receive xolair at a 3 active:1 placebo ratio	Drug: Xolair; Xolair is a monoclonal antibody approved by the FDA for asthma and chronic urticaria; Other Names: omalizumab
Placebo Comparator: Placebo This is a placebo that looks similar to Xolair and is given as a subcutaneous shot, just like Xolair	Drug: Placebo; Placebo

Outcome Measures

Primary Outcome Measures

1. Desensitization Measured by Proportion of Food Allergic (FA) Participants Who Pass a DBPCFC to 2,000 mg Protein for Each of 2 Allergens at Week 36 [36 weeks]

   Proportion of food allergic (FA) participants who pass a DBPCFC to 2,000 mg protein for each of 2 allergens at week 36. Xolair arm: 30/36 (83.3%) Placebo arm: 4/12 (33.3%)

Secondary Outcome Measures

1. Desensitization Measured to Increased Doses Measured by Proportion of FA Participants Who Pass a DBPCFC to 4,000 mg Each of 2 Allergens at Week 36 [36 weeks]

   Proportion of FA participants who pass a DBPCFC to 4,000 mg each of 2 allergens at week 36. Greater than 3 foods at 36 weeks for Xolair: 21/26 (80.8%) Placebo: 2/7 (28.6%)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 4 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Participant and/or parent guardian must be able to understand and provide informed consent and/or assent as applicable.

• Age 4 to 55 years with moderate to severe allergy to milk and/or egg and/or peanut and/or almond and/or wheat and/or cashew and/or sesame seed and/or soy and/or pecan and/or walnut and/or hazelnut

• ositive skin prick test result greater than or equal to 6 mm wheal diameter to each allergen OR

• ImmunoCAP IgE level >4kU/L for each allergen and

• A clinical reaction during a DBPCFC to small doses of food defined as < dose of 500 mg food protein

• No clinical reaction observed during the placebo (oat) challenge and

• If female, must have a negative urine pregnancy test on the same day (using a CLIA approved urine test)

• If female, of child-bearing potential, must agree to be compliant with a medically-approved method of contraception (please see Pregnancy section under Patient Disposition in this protocol)

• Plan to remain in the study area of the research center during the trial

• Be trained on the proper use of the Epinephrine autoinjector

• Avoid open or blinded food challenges to other allergens outside this study

Exclusion Criteria:

• Inability or unwillingness of a participant/parent/guardian to give written informed consent or comply with study protocol

• History of cardiovascular disease

• History of other chronic disease (other than asthma, atopic dermatitis, or rhinitis) requiring therapy (e.g., heart disease, diabetes) that, in the opinion of the Principal Investigator, would represent a risk to the participant's health or safety in this study or the participant's ability to comply with the study protocol

• A total IgE at screening of >1,500 kU/L

• Previous adverse reaction to Xolair

• A history of severe anaphylaxis (defined as requiring intubation or admission to an ICU) to food allergens that will be used in this study

• Unstable angina, significant arrhythmia, uncontrolled hypertension, current smokers, chronic sinusitis, or other chronic or immunological diseases that, in the judgment of the investigator, might interfere with the evaluation or administration of the test drug or pose additional risk to the participant.

• Current use of oral, intramuscular, or intravenous corticosteroids, tricyclic antidepressants, or beta-blockers (oral or topical)

• Routine use of medication that could induce adverse gastrointestinal reactions during the study

• Refusing to sign the Epinephrine autoinjector Training Form

• Pregnant or breast feeding women

• A history of oat allergy (since oat is the placebo agent in the DBPCFC), or an objective reaction to the screening DBPCFC to oat

• Unwilling to avoid all food allergen-containing items except those given as part of the OIT as well as any other food allergens you are allergic to that are not included in the 10 foods listed in the study

• Concurrent/prior use of immunomodulatory therapy (within 1 month) ie, omalizumab, non-traditional forms of allergen immunotherapy (e.g., oral or sublingual)

• Severe asthma (2007 NHLBI Criteria Steps 5 or 6) at time of enrollment

• Mild or moderate asthma (2007 NHLBI Criteria Steps 1-4) at time of enrollment with any of the following criteria met:

• FEV1 < 80% of predicted, or FEV1/FVC < 75%, with or without controller medications (only for age 6 or greater and able to do spirometry) or

• ICS dosing of > 220 mcg daily fluticasone (or equivalent inhaled corticosteroids based on NHLBI dosing chart) or

• 1 hospitalization in the past year for asthma or

• ER visit for asthma within the past six months

• Use of steroid medications (IV, IM or oral) in the following manners

• history of daily oral steroid dosing for >1 month during the past year or

• steroid burst course ( 5 or more days) of 1 mg/kg prednisone) course in the past 3 months or

• 2 steroid burst courses in the past year

• Use of complementary and alternative medicine (CAM) treatment modalities (e.g., herbal remedies) for atopic and/or non-atopic disease within 90 days preceding rush desensitization at week 8or at any time .

• Inability to discontinue antihistamines for the initial day of escalation, skin testing or OFCs

• Use of investigational drugs within 24 weeks of participation

• Past or current medical problems or findings from physical assessment or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sean N Parker Allergy Reseach Center at Stanford University	Mountain View	California	United States	94040

Sponsors and Collaborators

• Stanford University
• National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

• Study Director: Kari Nadeau, MD PhD, Stanford University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Kari Christine Nadeau, Protocol Director, Stanford University
• ClinicalTrials.gov Identifier: NCT02643862
• Other Study ID Numbers: 123; U19AI104209
• First Posted: Dec 31, 2015
• Last Update Posted: Jan 12, 2018
• Last Verified: Dec 1, 2017

• Additional relevant MeSH terms: Food Hypersensitivity; Omalizumab

Study Results

Participant Flow

Arm/Group Title	Xolair	Placebo
Arm/Group Description	Pts will be randomized to receive xolair at a 3 active:1 placebo ratio Xolair: Xolair is a monoclonal antibody approved by the FDA for asthma and chronic urticaria	This is a placebo that looks similar to Xolair and is given as a subcutaneous shot, just like Xolair Xolair: Xolair is a monoclonal antibody approved by the FDA for asthma and chronic urticaria
Period Title: Overall Study
STARTED	36	12
COMPLETED	36	12
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Xolair	Placebo	Total
Arm/Group Description	Pts will be randomized to receive xolair at a 3 active:1 placebo ratio Xolair: Xolair is a monoclonal antibody approved by the FDA for asthma and chronic urticaria	This is a placebo that looks similar to Xolair and is given as a subcutaneous shot, just like Xolair Xolair: Xolair is a monoclonal antibody approved by the FDA for asthma and chronic urticaria	Total of all reporting groups
Overall Participants	36	12	48
Age (Count of Participants)
<=18 years	36 100%	12 100%	48 100%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	8	7	8
Sex: Female, Male (Count of Participants)
Female	18 50%	6 50%	24 50%
Male	18 50%	6 50%	24 50%
Region of Enrollment (participants) [Number]
United States	36 100%	12 100%	48 100%

Outcome Measures

1. Primary Outcome

Title	Desensitization Measured by Proportion of Food Allergic (FA) Participants Who Pass a DBPCFC to 2,000 mg Protein for Each of 2 Allergens at Week 36
Description	Proportion of food allergic (FA) participants who pass a DBPCFC to 2,000 mg protein for each of 2 allergens at week 36. Xolair arm: 30/36 (83.3%) Placebo arm: 4/12 (33.3%)
Time Frame	36 weeks

Outcome Measure Data

Analysis Population Description

this is an ITT population

Arm/Group Title	Xolair	Placebo
Arm/Group Description	Pts will be randomized to receive xolair at a 3 active:1 placebo ratio Xolair: Xolair is a monoclonal antibody approved by the FDA for asthma and chronic urticaria	This is a placebo that looks similar to Xolair and is given as a subcutaneous shot, just like Xolair Xolair: Xolair is a monoclonal antibody approved by the FDA for asthma and chronic urticaria
Measure Participants	36	12
Count of Participants [Participants]	30 83.3%	4 33.3%

2. Secondary Outcome

Title	Desensitization Measured to Increased Doses Measured by Proportion of FA Participants Who Pass a DBPCFC to 4,000 mg Each of 2 Allergens at Week 36
Description	Proportion of FA participants who pass a DBPCFC to 4,000 mg each of 2 allergens at week 36. Greater than 3 foods at 36 weeks for Xolair: 21/26 (80.8%) Placebo: 2/7 (28.6%)
Time Frame	36 weeks

Outcome Measure Data

Analysis Population Description

We analyzed an ITT

Arm/Group Title	Xolair	Placebo
Arm/Group Description	Pts will be randomized to receive xolair at a 3 active:1 placebo ratio Xolair: Xolair is a monoclonal antibody approved by the FDA for asthma and chronic urticaria	This is a placebo that looks similar to Xolair and is given as a subcutaneous shot, just like Xolair Xolair: Xolair is a monoclonal antibody approved by the FDA for asthma and chronic urticaria
Measure Participants	26	7
Count of Participants [Participants]	21 58.3%	2 16.7%

Adverse Events

Time Frame	AEs were collected over the entire course of the active study
Adverse Event Reporting Description	The same definitions of AE and SAE were used as per clinicaltrials.gov
Arm/Group Title	Xolair		Placebo
Arm/Group Description	Pts will be randomized to receive xolair at a 3 active:1 placebo ratio Xolair: Xolair is a monoclonal antibody approved by the FDA for asthma and chronic urticaria		This is a placebo that looks similar to Xolair and is given as a subcutaneous shot, just like Xolair Xolair: Xolair is a monoclonal antibody approved by the FDA for asthma and chronic urticaria
All Cause Mortality
	Xolair		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/36 (0%)		0/12 (0%)
Serious Adverse Events
	Xolair		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/36 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	Xolair		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	33/36 (91.7%)		12/12 (100%)
Skin and subcutaneous tissue disorders
urticaria	33/36 (91.7%)	106	12/12 (100%)	28

Limitations/Caveats

The mechanistic 12 controls are not part of the randomization. The arms that are randomized are 48*. Mechanistic controls did not undergo therapy.

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.