Multi Immunotherapy to Test Tolerance and Xolair | NCT02626611

NCT02626611

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Name	Class
Icahn School of Medicine at Mount Sinai	OTHER
Children's Hospital of Philadelphia	OTHER
Ann & Robert H Lurie Children's Hospital of Chicago	OTHER

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Placebo	Placebo Comparator	Xolair will be administered in week 0 through 16 of the study. Starting at week 8, food doses will be serially increased, per protocol, to up to 2000 milligrams per food. At week 30, the cohort will be randomized into 3 groups (placebo, low dose food, and high dose food). Participants will continue on this dose for 6 weeks. The oat placebo food, will be compared to high dose (2000 milligrams or low dose 300 milligrams food immunotherapy). At week 36 a food challenge will be performed to assess study endpoints.	Drug: Omalizumab Drug: Food Flour Buildup
Low Dose Food	Active Comparator	Xolair will be administered in week 0 through 16 of the study. Starting at week 8, food doses will be serially increased, per protocol, to up to 2000 milligrams per food. At week 30, the cohort will be randomized into 3 groups (placebo, low dose food, and high dose food). Participants will continue on this dose for 6 weeks. The oat placebo food, will be compared to high dose (2000 milligrams or low dose 300 milligrams food immunotherapy). At week 36 a food challenge will be performed to assess study endpoints.	Drug: Omalizumab Drug: Food Flour Buildup
High Dose Food	Active Comparator	Xolair will be administered in week 0 through 16 of the study. Starting at week 8, food doses will be serially increased, per protocol, to up to 2000 milligrams per food. At week 30, the cohort will be randomized into 3 groups (placebo, low dose food, and high dose food). Participants will continue on this dose for 6 weeks. The oat placebo food, will be compared to high dose (2000 milligrams or low dose 300 milligrams food immunotherapy). At week 36 a food challenge will be performed to assess study endpoints.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Omalizumab	Drug	Omalizumab is an anti-Immunoglobulin E antibody injection and will be administered per product insert from weeks 0 through 16 of the study.	High Dose Food

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
The Number of Participants Able to Tolerate an Oral Food Challenge to 2,000 mg at Least of 2 Allergens at Week 36 (i.e. the End of the Randomized Withdrawal/Tolerance Phase), Will be Reported.	Number of FA participants who pass a DBPCFC to 2,000 mg each of 2 allergens (i.e. no reaction of grade 1 or more according to Bock's criteria) at week 36, will be reported.	36 weeks

Secondary Outcomes

Measure	Description	Time Frame
The Number of Participants Able to Tolerate an Oral Dose of 4,000mg Each of 2 Allergens Separately at Week 36, Will be Reported.	Number of FA participants who pass a DBPCFC to (4,000 mg each of 2 allergens at week 36) (i.e. no reaction of grade 1 or more according to Bock's criteria) .	36 weeks
The Number of Participants Able to Tolerate an Oral Dose of 2,000mg Each of 3 Allergens (When Applicable) Separately at Week 36, Will be Reported.

Eligibility Module

Eligibility Criteria

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
Positive skin prick test result greater than or equal to 6 mm wheal diameter to each allergen OR
ImmunoCAP Immunoglobulin E (IgE) level >4 kilo Unit/Liter 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 Clinical Laboratory Improvement Amendment (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 >2,000 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 betablockers (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 Oral Immunotherapy 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, nontraditional forms of allergen immunotherapy (e.g., oral or sublingual)
Severe asthma (2007 National Heart Lung and Blood Institute (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:
Forced Expiratory Volume at one second (FEV1) < 80% of predicted, or FEV1/Forced Vital Capacity (FVC) < 75%, with or without controller medications (only for age 6 or greater and able to do spirometry) or
Inhaled Corticosteroid (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 (Intravenous (IV), Intramuscular (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 Oral Food Challenges (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.

Name	Affiliation	Role
Nadeau C Nadeau, MD PhD	Stanford University	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Children's Hospital of Los Angeles		Los Angeles	California	90027	United States
Sean N. Parker Center for Allergy Research at Stanford University

PubMed Identifier	Type	Citation	Retractions
31193674	Derived	Andorf S, Purington N, Kumar D, Long A, O'Laughlin KL, Sicherer S, Sampson H, Cianferoni A, Whitehorn TB, Petroni D, Makhija M, Robison RG, Lierl M, Logsdon S, Desai M, Galli SJ, Rael E, Assa'ad A, Chinthrajah S, Pongracic J, Spergel JM, Tam J, Tilles S, Wang J, Nadeau K. A Phase 2 Randomized Controlled Multisite Study Using Omalizumab-facilitated Rapid Desensitization to Test Continued vs Discontinued Dosing in Multifood Allergic Individuals. EClinicalMedicine. 2019 Jan 21;7:27-38. doi: 10.1016/j.eclinm.2018.12.006. eCollection 2019 Jan.

Arm/Group Information

ID	Title	Description
FG000	Placebo	Xolair will be administered in week 0 through 16 of the study. Starting at week 8, food doses will be serially increased, per protocol, to up to 2000 milligrams per food. At week 30, the cohort will be randomized into 3 groups (placebo, low dose food, and high dose food). Participants will continue on this dose for 6 weeks. The oat placebo food, will be compared to high dose (2000 milligrams or low dose 300 milligrams food immunotherapy). At week 36 a food challenge will be performed to assess study endpoints. Omalizumab: Omalizumab is administered per product insert from weeks 0 -16 of the study. Food Flour Buildup: Food flours identified as allergic (based on food challenge), will be introduced at week 8. The food dose will be escalated every 2 weeks up to 2000 milligrams of each of the food flours. Subjects are required to reach 300 milligrams at week 16 to continue to week 30. Subjects must tolerate 2000 milligrams per food by week 28 in order to be randomized.
FG001	Low Dose Food	Xolair will be administered in week 0 through 16 of the study. Starting at week 8, food doses will be serially increased, per protocol, to up to 2000 milligrams per food. At week 30, the cohort will be randomized into 3 groups (placebo, low dose food, and high dose food). Participants will continue on this dose for 6 weeks. The oat placebo food, will be compared to high dose (2000 milligrams or low dose 300 milligrams food immunotherapy). At week 36 a food challenge will be performed to assess study endpoints. Omalizumab: Omalizumab is administered per product insert from weeks 0 -16 of the study. Food Flour Buildup: Food flours identified as allergic (based on food challenge), will be introduced at week 8. The food dose will be escalated every 2 weeks up to 2000 milligrams of each of the food flours. Subjects are required to reach 300 milligrams at week 16 to continue to week 30. Subjects must tolerate 2000 milligrams per food by week 28 in order to be randomized.
FG002	High Dose Food	Xolair will be administered in week 0 through 16 of the study. Starting at week 8, food doses will be serially increased, per protocol, to up to 2000 milligrams per food. At week 30, the cohort will be randomized into 3 groups (placebo, low dose food, and high dose food). Participants will continue on this dose for 6 weeks. The oat placebo food, will be compared to high dose (2000 milligrams or low dose 300 milligrams food immunotherapy). At week 36 a food challenge will be performed to assess study endpoints. Omalizumab: Omalizumab is administered per product insert from weeks 0 - 16 of the study. Food Flour Buildup: Food flours identified as allergic (based on food challenge), will be introduced at week 8. The food dose will be escalated every 2 weeks up to 2000 milligrams of each of the food flours. Subjects are required to reach 300 milligrams at week 16 to continue to week 30. Subjects must tolerate 2000 milligrams per food by week 28 in order to be randomized.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Placebo	Xolair will be administered in week 0 through 16 of the study. Starting at week 8, food doses will be serially increased, per protocol, to up to 2000 milligrams per food. At week 30, the cohort will be randomized into 3 groups (placebo, low dose food, and high dose food). Participants will continue on this dose for 6 weeks. The oat placebo food, will be compared to high dose (2000 milligrams or low dose 300 milligrams food immunotherapy). At week 36 a food challenge will be performed to assess study endpoints. Omalizumab: Omalizumab is administered per product insert from weeks 0 -16 of the study. Food Flour Buildup: Food flours identified as allergic (based on food challenge), will be introduced at week 8. The food dose will be escalated every 2 weeks up to 2000 milligrams of each of the food flours. Subjects are required to reach 300 milligrams at week 16 to continue to week 30. Subjects must tolerate 2000 milligrams per food by week 28 in order to be randomized.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

The Number of Participants Able to Tolerate an Oral Food Challenge to 2,000 mg at Least of 2 Allergens at Week 36 (i.e. the End of the Randomized Withdrawal/Tolerance Phase), Will be Reported.

Number of FA participants who pass a DBPCFC to 2,000 mg each of 2 allergens (i.e. no reaction of grade 1 or more according to Bock's criteria) at week 36, will be reported.

Posted

Count of Participants

Participants

36 weeks

ID	Title	Description
OG000	Placebo	Xolair will be administered in week 0 through 16 of the study. Starting at week 8, food doses will be serially increased, per protocol, to up to 2000 milligrams per food. At week 30, the cohort will be randomized into 3 groups (placebo, low dose food, and high dose food). Participants will continue on this dose for 6 weeks. The oat placebo food, will be compared to high dose (2000 milligrams or low dose 300 milligrams food immunotherapy). At week 36 a food challenge will be performed to assess study endpoints. Omalizumab: Omalizumab is administered per product insert from weeks 0 -16 of the study. Food Flour Buildup: Food flours identified as allergic (based on food challenge), will be introduced at week 8. The food dose will be escalated every 2 weeks up to 2000 milligrams of each of the food flours. Subjects are required to reach 300 milligrams at week 16 to continue to week 30. Subjects must tolerate 2000 milligrams per food by week 28 in order to be randomized.

ID	Term
D006969	Hypersensitivity, Immediate
D006967	Hypersensitivity
D007154	Immune System Diseases

ID	Term
D000888	Antibodies, Anti-Idiotypic
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins