Omalizumab as Monotherapy and as Adjunct Therapy to Multi-Allergen OIT in Food Allergic Participants

NCT ID: NCT03881696

Last Updated: 2025-09-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 471 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-07-22
• Study Completion Date: 2025-07-01

Brief Summary

This study is a multi-center, randomized, double-blind, placebo-controlled study in participants 1 to less than 56 years of age who are allergic to peanut and at least two other foods (including milk, egg, wheat, cashew, hazelnut, or walnut). While each participant may be allergic to more than two other foods, the primary endpoint/outcome in this study will only be assessed in peanut and two other foods for each participant. The primary objective of the study is to compare the ability to consume foods without dose-limiting symptoms during a double-blind placebo-controlled food challenge (DBPCFC), after treatment with either omalizumab or placebo for omalizumab.

Detailed Description

Food allergy affects about 15 million people in the United States. This includes 6 million children. The current treatment for food allergy is to avoid eating the foods that may cause an allergic reaction and have medications such as epinephrine (adrenaline) in case of a reaction. However, accidental exposures can be extremely difficult to avoid, particularly if you are allergic to multiple foods. The risks of accidental exposures and life-threatening reactions can place a large burden on patients and their families.

Investigators in this study would like to learn if omalizumab injections alone or in combination with multi-allergen oral immunotherapy (OIT) will help people with multiple food allergies eat foods to which they are allergic. Oral means that you will take the food allergen (peanut and 2 other foods to which you are allergic) by mouth. If you are allergic to more than 3 foods, this study will only provide OIT for peanut and 2 other foods.

There are 3 stages to the study:

In Stage 1, investigators would like to learn:

• If omalizumab stops or decreases allergic reactions to peanut and other common food allergens after taking it for a length of time.

Stage 1 will also have an extra part so that 60 participants will receive omalizumab and everyone (the investigators conducting the research and study participants) will know it. This is why it is called the open label extension. This part of the study will assist investigators in learning if receiving omalizumab for a longer time may work better at decreasing allergic reactions.

In Stage 2, investigators would like to learn:

• How a short course of omalizumab combined with Multi-allergen OIT compares with a longer course of omalizumab in decreasing allergic reactions.

In Stage 3, investigators would like to learn:

• If, after participants stop both treatments, will they be able to eat the peanut and the 2 other foods in the form that is normally eaten.

In all stages, investigators would like to learn:

• How safe and effective the treatments are and
• How the OIT affects the immune system.

Participation will last up to 56 months (4 years and 8 months).

Conditions

Peanut Allergy; Multi-food Allergy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Stage 1:Omalizumab as Monotherapy

Eligible participants are randomized to receive omalizumab by subcutaneous injection either every 2 weeks or every 4 weeks for 16 to 20 weeks. The dose administered and the dosing interval are determined by serum total IgE level and body weight (measured before the start of treatment) per the study drug dosing table.

After 16 weeks of treatment, each participant will complete double-blind placebo-controlled food challenge (DBPCFCs) to each of their three specific foods to a cumulative dose of 6044 mg protein of each food.

Throughout Stage 1, each participant will be instructed to strictly avoid all foods to which they are allergic.

The first 60 participants who complete all four DBPCFCs at the end of Stage 1 will participate in the Stage 1 Open Label Extension (OLE).All other participants who complete all four DBPCFCs will move Stage 2 of the study.

Group Type: EXPERIMENTAL

Omalizumab

Intervention Type: DRUG

Omalizumab will be supplied in pre-filled syringes (PFS). PFS of omalizumab will be provided to the clinical research units as 75 mg and 150 mg dosage forms.

Stage 1: Omalizumab OLE

OLE: Open Label Extension, Long-Term Treatment with Omalizumab. Participants will receive 24 weeks of open label omalizumab in accordance with the omalizumab dosing table defined in the study protocol. Omalizumab is administered by subcutaneous injection either every 2 weeks or every 4 weeks for 24 weeks. The dose administered and the dosing interval are determined by serum total IgE level and body weight (measured before the start of treatment) per the study drug dosing table.

After 24 weeks of treatment, each participant will complete DBPCFCs to each of their three specific foods to a cumulative dose of 8044 mg protein of each food. Each participant who completes all four DBPCFCs at the end of the Stage 1 OLE will move on to Stage 3 of the study.

Throughout Stage 1 OLE, each participant will be instructed to strictly avoid all foods to which they are allergic.

Group Type: EXPERIMENTAL

Omalizumab

Intervention Type: DRUG

Omalizumab will be supplied in pre-filled syringes (PFS). PFS of omalizumab will be provided to the clinical research units as 75 mg and 150 mg dosage forms.

Stage 1: Placebo for Omalizumab as Monotherapy

Eligible participants are randomized to receive placebo for omalizumab by subcutaneous injection either every 2 weeks or every 4 weeks for 16 to 20 weeks. The dose administered and the dosing interval are determined by serum total IgE level and body weight (measured before the start of treatment) per the study drug dosing table.

After 16 weeks of treatment, each participant will complete DBPCFCs to each of their three specific foods to a cumulative dose of 6044 mg protein of each food.

Throughout Stage 1, each participant will be instructed to strictly avoid all foods to which they are allergic.

The first 60 participants who complete all four DBPCFCs at the end of Stage 1 will participate in the Stage 1 OLE. All other participants who complete all four DBPCFCs will move Stage 2 of the study.

Group Type: PLACEBO_COMPARATOR

Placebo for Omalizumab

Intervention Type: DRUG

Placebo contains the same ingredients as the omalizumab formulation, excluding omalizumab. Placebo will be supplied in pre-filled syringes (PFS). PFS of placebo will be provided to the clinical research units as 75 mg and 150 mg dosage forms.

Stage 2: Omalizumab

Participants will receive eight weeks of treatment with open label omalizumab in accordance with the omalizumab dosing table specified in the study protocol, administered by subcutaneous injection. The dose administered and the dosing interval are determined by serum total IgE level and body weight (measured before the start of treatment) per the study drug dosing table.

After completion of eight weeks of open label omalizumab, participants will be randomized 1:1 to either:

• Omalizumab-facilitated oral immunotherapy (OIT): Open label omalizumab + Multi-allergen OIT for eight weeks, followed by placebo for omalizumab + Multi-allergen OIT for 44 weeks OR
• Omalizumab + placebo OIT: Open label omalizumab + placebo for Multi-allergen OIT for eight weeks, followed by omalizumab + placebo for Multi-allergen OIT for 44 weeks.

Throughout Stage 2, each participant will be instructed to strictly avoid all foods to which they are allergic.

Group Type: EXPERIMENTAL

Omalizumab

Intervention Type: DRUG

Omalizumab will be supplied in pre-filled syringes (PFS). PFS of omalizumab will be provided to the clinical research units as 75 mg and 150 mg dosage forms.

Stage 2: Omalizumab-Facilitated OIT

OIT: oral immunotherapy-Omalizumab as Adjunct Therapy to Multi-Allergen Oral Immunotherapy

Participants randomized to open label omalizumab + Multi-allergen OIT for eight weeks, followed by placebo for omalizumab + Multi-allergen OIT for 44 weeks.

Throughout Stage 2, each participant will be instructed to strictly avoid all foods to which they are allergic.

Group Type: EXPERIMENTAL

Omalizumab

Intervention Type: DRUG

Omalizumab will be supplied in pre-filled syringes (PFS). PFS of omalizumab will be provided to the clinical research units as 75 mg and 150 mg dosage forms.

Multi-Allergen Oral Immunotherapy

Intervention Type: DRUG

Multi-allergen OIT will be any of the following drug products: peanut, milk, egg, wheat, cashew, hazelnut, and walnut (all food protein flours).

A prescription for each participant for the appropriate dose of each of the allergens will be prepared. The pharmacist will compound the appropriate allergens and dispense the Multi-allergen OIT dose in a blinded (masked) fashion. The Clinical Research Unit (CRU) staff will administer food flour to the participant orally in an age-appropriate food vehicle (e.g., applesauce, pudding, etc.). Dosage will be administered according to the study protocol.

Stage 2: Omalizumab + Placebo OIT

OIT: oral immunotherapy Participants randomized to open label omalizumab + placebo for Multi-allergen OIT for eight weeks, followed by omalizumab + placebo for Multi-allergen OIT for 44 weeks.

Throughout Stage 2, each participant will be instructed to strictly avoid all foods to which they are allergic.

Group Type: EXPERIMENTAL

Omalizumab

Intervention Type: DRUG

Omalizumab will be supplied in pre-filled syringes (PFS). PFS of omalizumab will be provided to the clinical research units as 75 mg and 150 mg dosage forms.

Placebo for Multi-Allergen Oral Immunotherapy

Intervention Type: DRUG

Oat flour will be used for placebo for Multi-allergen OIT. Route: by mouth/oral. Dosage will be administered according to the study protocol.

Stage 3: DBPCFC Based Treatment

DBPCFC Based Treatment-Long-term Follow-up Treatment Plan for Peanut and Each of the Two Other Participant-Specific Foods.

Upon completion of the DBPCFCs at the end of Stage 1 OLE or Stage 2, each participant will receive a separate treatment plan for peanut and each of the two other participant-specific foods based on the results of the DBPCFCs. A treatment plan will include instructions for one of the following:

• Long-term follow-up with dietary consumption of a food;
• Long-term follow-up with avoidance of a food; or
• Rescue OIT for a food.

The treatment plan for each food may change throughout Stage 3 depending on a participant's response to treatment. Once a participant enters Stage 3, the participant will have a minimum of 12 months follow-up until at least December 2022.

Note: Participants will be instructed to strictly avoid a food if they receive rescue OIT for the food during Stage 3.

Group Type: OTHER

Double-Blind Placebo-Controlled Food Challenge Based Treatment

Intervention Type: OTHER

Each participant will receive a separate treatment plan for peanut and each of the two other participant-specific foods. A treatment plan will include instructions for one of the following:

• Long-term follow-up with dietary consumption of a food; or
• Long-term follow-up with avoidance of a food; or
• Rescue OIT for a food. The treatment plan for each food may change depending on a participant's response to prescribed treatment over time.

Interventions

Omalizumab

Omalizumab will be supplied in pre-filled syringes (PFS). PFS of omalizumab will be provided to the clinical research units as 75 mg and 150 mg dosage forms.

Intervention Type: DRUG

Placebo for Omalizumab

Placebo contains the same ingredients as the omalizumab formulation, excluding omalizumab. Placebo will be supplied in pre-filled syringes (PFS). PFS of placebo will be provided to the clinical research units as 75 mg and 150 mg dosage forms.

Intervention Type: DRUG

Multi-Allergen Oral Immunotherapy

Multi-allergen OIT will be any of the following drug products: peanut, milk, egg, wheat, cashew, hazelnut, and walnut (all food protein flours).

A prescription for each participant for the appropriate dose of each of the allergens will be prepared. The pharmacist will compound the appropriate allergens and dispense the Multi-allergen OIT dose in a blinded (masked) fashion. The Clinical Research Unit (CRU) staff will administer food flour to the participant orally in an age-appropriate food vehicle (e.g., applesauce, pudding, etc.). Dosage will be administered according to the study protocol.

Intervention Type: DRUG

Placebo for Multi-Allergen Oral Immunotherapy

Oat flour will be used for placebo for Multi-allergen OIT. Route: by mouth/oral. Dosage will be administered according to the study protocol.

Intervention Type: DRUG

Double-Blind Placebo-Controlled Food Challenge Based Treatment

Each participant will receive a separate treatment plan for peanut and each of the two other participant-specific foods. A treatment plan will include instructions for one of the following:

• Long-term follow-up with dietary consumption of a food; or
• Long-term follow-up with avoidance of a food; or
• Rescue OIT for a food. The treatment plan for each food may change depending on a participant's response to prescribed treatment over time.

Intervention Type: OTHER

Other Intervention Names

Xolair®; Placebo; Multi-Allergen OIT; Placebo for Multi-Allergen OIT; DBPCFC Based Treatment

Eligibility Criteria

Inclusion Criteria

Individuals who meet all of the following criteria are eligible for enrollment as study participants:

1. Participant and/or parent/legal guardian must be able to understand and provide informed consent and/or assent, as applicable;

2. Peanut allergic: participant must meet all of the following criteria to minimize the chance that the participant will develop natural tolerance to peanut over the course of the study:

1. Positive skin prick test (SPT) defined as ≥4 mm wheal greater than saline control) to peanut,

2. Positive peanut immunoglobulin E (IgE), ≥6 kUA/L, at Screening or within three months of Screening, determined by ImmunoCap, and

3. Positive double-blind placebo-controlled food challenge (DBPCFC), defined as experiencing dose-limiting symptoms at a single dose of ≤100 mg of peanut protein.

3. Allergic to at least two of the six other foods (milk, egg, wheat, cashew, hazelnut, walnut): each participant must meet all of the following criteria for at least two of the six other foods to minimize the chance that the participant will develop natural tolerance to at least two of the six other foods over the course of the study:

1. Positive SPT (≥4 mm wheal) to food,

2. Positive food specific IgE (≥6 kUA/L) at Screening or within three months of Screening, determined by ImmunoCap, and

3. Positive DBPCFC, defined as experiencing dose-limiting symptoms at a single dose of ≤300 mg of food protein.

4. With body weight (as measured at Screening) and total serum IgE level (as measured within three months of Screening) suitable for omalizumab dosing;

5. If female of child-bearing potential, must have a negative urine or serum pregnancy test;

6. For women of childbearing potential, must agree to,during the treatment period and for 60 days after the last dose of study drug:

• remain abstinent (refrain from heterosexual intercourse), or
• use acceptable contraceptive methods (barrier methods, or
• oral, injected, or implanted hormonal methods of contraception, or
• other forms of hormonal contraception that have comparable efficacy).

7. Plan to remain in the study area of an OUtMATCH clinical research unit (CRU) during the trial; and

8. Be willing to be trained on the proper use of an epinephrine autoinjector for the duration of the study.

Exclusion Criteria

Individuals who meet any of the following criteria are not eligible for enrollment as study participants:

1. Inability or unwillingness of a participant and/or parent/legal guardian to give written informed consent and/or assent or comply with the study protocol;

2. Clinically significant laboratory abnormalities at Screening;

3. Dose-limiting symptoms to the placebo portion of the Screening DBPCFC;

4. Sensitivity or suspected/known allergy to any ingredients (including excipients) of the

• active or placebo oral food challenge (OFC) material,
• multi-allergen oral immunotherapy (OIT), or
• drugs related to omalizumab (e.g., monoclonal antibodies, polyclonal gamma globulin).

• Note: Guidance for determination of sensitivity to excipients will be detailed in the study's Manual of Procedures (MOP).

5. Poorly controlled atopic dermatitis (AD) at Screening, per the Principal Investigator's PI's) discretion;

6. Poorly controlled or severe asthma/wheezing at Screening, defined by at least one of the following criteria:

1. Global Initiative for Asthma (GINA) criteria regarding asthma control latest guidelines,

2. History of two or more systemic corticosteroid courses within six months of Screening or one course of systemic corticosteroids within three months of Screening to treat asthma/wheezing,

3. Prior intubation/mechanical ventilation for asthma/wheezing,

4. One hospitalization or Emergency Department (ED) visit for asthma/wheezing within six months of Screening,

5. Forced expiratory volume in one second (FEV1) <80 percent of predicted or FEV1/forced vital capacity (FVC) <75 percent, with or without controller medications (only for participants who are aged seven years or older and are able to perform spirometry), or

6. Inhaled corticosteroid (ICS) dosing of >500 mcg daily fluticasone (or equivalent ICS based on the National Institutes of Health, National Heart, Lung, and Blood Institute (NHLBI) dosing chart).

7. History of severe anaphylaxis to participant-specific foods that will be used in this study, defined as neurological compromise or requiring intubation;

8. Treatment with a burst of oral, intramuscular (IM), or intravenous (IV) steroids of more than two days for an indication other than asthma/wheezing within 30 days of Screening;

9. Currently receiving oral, intramuscular, or intravenous corticosteroids, tricyclic antidepressants, or beta-blockers (oral or topical);

10. Past or current history of eosinophilic gastrointestinal (GI) disease within three years of Screening;

11. Past or current history of cancer, or currently being investigated for possible cancer;

12. Previous adverse reaction to omalizumab;

13. Past or current history of any immunotherapy to any of the foods being treated in this study (e.g., OIT, sublingual immunotherapy [SLIT], EPIT) within 6 months of Screening;

14. Treatment with monoclonal antibody therapy, such as omalizumab (Xolair®), dupilumab (Dupixent®), benralizumab (Fasenra™), mepolizumab (Nucala®), reslizumab (Cinqair®), or other immunomodulatory therapy within six months of Screening;

15. Currently on "build-up phase" of inhalant allergen immunotherapy (i.e., has not reached maintenance dosing). Note: Individuals tolerating maintenance allergen immunotherapy can be enrolled;

16. Inability to discontinue antihistamines for the minimum wash-out periods required for SPTs,or OFCs;

17. Current participation in another therapeutic or interventional clinical trial or participation within 90 days of Screening;

18. Use of investigational drugs within 24 weeks of Screening;

19. Pregnant or breastfeeding, or intending to become pregnant during the study or within 60 days after the last dose of omalizumab or placebo for omalizumab;

20. Has a first-degree relative already enrolled in the study; or

21. Past or current medical problems (e.g., severe latex allergy), history of other chronic diseases (other than asthma/wheezing, AD, or rhinitis) requiring therapy (e.g., heart disease, diabetes), findings from physical assessment, or abnormalities in clinical laboratory testing that are not listed above, which, in the opinion of the PI, may:

• pose additional risks from participation in the study,
• may interfere with the participant's ability to comply with study requirements, or
• may impact the quality or interpretation of the data obtained from the study.

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genentech, Inc.

INDUSTRY

Sponsor Role: collaborator

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Rho Federal Systems Division, Inc.

INDUSTRY

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Robert A. Wood, MD

Role: STUDY_CHAIR

Department of Pediatrics at the Johns Hopkins University School of Medicine

Sharon Chinthrajah, MD

Role: STUDY_CHAIR

Department of Medicine, Stanford University School of Medicine

Locations

Arkansas Children's Hospital Research Institute: Department of Pediatrics, Allergy & Immunology

Little Rock, Arkansas, United States

Stanford School of Medicine: Sean N. Parker Center for Allergy & Asthma Research

Stanford, California, United States

National Jewish Health: Division of Pediatric Allergy and Clinical Immunology

Denver, Colorado, United States

Emory University School of Medicine: Children's Healthcare of Atlanta Pediatrics

Atlanta, Georgia, United States

Johns Hopkins Children's Center: Department of Allergy & Immunology

Baltimore, Maryland, United States

Massachusetts General Hospital, Department of Medicine: Allergy & Clinical Immunology Unit

Boston, Massachusetts, United States

Icahn School of Medicine at Mount Sinai: Department of Pediatrics Allergy & Immunology

New York, New York, United States

North Carolina Children's Hospital: Department of Pediatrics, Division of Allergy, Immunology and Rheumatology

Chapel Hill, North Carolina, United States

Children's Hospital of Philadelphia: Division of Allergy and Immunology

Philadelphia, Pennsylvania, United States

University of Texas Southwestern Medical Center: Division of Allergy and Immunology

Dallas, Texas, United States

Countries

United States

References

Sampson HA, Berin MC, Plaut M, Sicherer SH, Jones S, Burks AW, Lindblad R, Leung DYM, Wood RA. The Consortium for Food Allergy Research (CoFAR): The first generation. J Allergy Clin Immunol. 2019 Feb;143(2):486-493. doi: 10.1016/j.jaci.2018.12.989. Epub 2018 Dec 23.

Reference Type: BACKGROUND

PMID: 30586557 (View on PubMed)

Wood RA, Togias A, Sicherer SH, Shreffler WG, Kim EH, Jones SM, Leung DYM, Vickery BP, Bird JA, Spergel JM, Iqbal A, Olsson J, Ligueros-Saylan M, Uddin A, Calatroni A, Huckabee CM, Rogers NH, Yovetich N, Dantzer J, Mudd K, Wang J, Groetch M, Pyle D, Keet CA, Kulis M, Sindher SB, Long A, Scurlock AM, Lanser BJ, Lee T, Parrish C, Brown-Whitehorn T, Spergel AKR, Veri M, Hamrah SD, Brittain E, Poyser J, Wheatley LM, Chinthrajah RS. Omalizumab for the Treatment of Multiple Food Allergies. N Engl J Med. 2024 Mar 7;390(10):889-899. doi: 10.1056/NEJMoa2312382. Epub 2024 Feb 25.

Reference Type: RESULT

PMID: 38407394 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Related Links

http://www.niaid.nih.gov/about/dait

Division of Allergy, Immunology, and Transplantation

http://www.niaid.nih.gov/

National Institute of Allergy and Infectious Diseases

Other Identifiers

CoFAR-11

Identifier Type: OTHER

Identifier Source: secondary_id

NIAID CRMS ID#: 38625

Identifier Type: OTHER

Identifier Source: secondary_id

DAIT CoFAR-11

Identifier Type: -

Identifier Source: org_study_id