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

NCT03881696 | Completed Phase 3 Results DMC FDA Drug

• 3 other identifiers: DAIT CoFAR-11CoFAR-11NIAID CRMS ID#: 38625
• Study Type: interventional
• Target: 471
• Locations: 1 country
• Sites: 10

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.

Conditions

Peanut Allergy; Multi-food Allergy

Keywords

peanut allergic; multi-food allergic; omalizumab; placebo; multi-allergen oral immunotherapy (OIT); double-blind placebo-controlled food challenge (DBPCFC); oral food challenge (OFC)

Outcome Measures

Primary Outcomes (1)

• Number of Participants by Stage 1 Treatment Assignment, Omalizumab Versus Placebo, Who Successfully Consume a Single Dose of ≥600 mg of Peanut Protein Without Dose-Limiting Symptoms During the DBPCFC Conducted at the End of Treatment Stage 1

  Number of participants who successfully consume a single dose of ≥600 mg of peanut protein without dose-limiting symptoms during the double-blind placebo-controlled oral food challenge (DBPCFC) conducted in a controlled clinic setting, at the end of Stage 1 treatment, to compare the ability of participants to consume foods without dose-limiting symptoms during a DBPCFC after treatment with either omalizumab or placebo for omalizumab. Dose-limiting symptoms are those that in the view of the principal investigator indicate a true allergic reaction.

  During the DBPCFC at the end of Stage 1: 16 to 20 weeks after Stage 1 treatment initiation

Secondary Outcomes (95)

• Number of Participants by Stage 1 Treatment Assignment, Omalizumab Versus Placebo, Who Successfully Consume a Single Dose of ≥1000 mg of Cashew Protein Without Dose-limiting Symptoms During the DBPCFC Conducted at the End of Stage 1

  During the DBPCFC at the end of Stage 1: 16 to 20 weeks after Stage 1 treatment initiation

• Number of Participants by Stage 1 Treatment Assignment, Omalizumab Versus Placebo, Who Successfully Consume a Single Dose of ≥1000 mg of Milk Protein Without Dose-limiting Symptoms During the DBPCFC at the End of Stage 1

  During the DBPCFC at the end of Stage 1: 16 to 20 weeks after Stage 1 treatment initiation

• Number of Participants by Stage 1 Treatment Assignment, Omalizumab Versus Placebo, Who Successfully Consume a Single Dose of ≥1000 mg of Egg Protein Without Dose-limiting Symptoms During the DBPCFC at the End of Stage 1

  During the DBPCFC at the end of Stage 1: 16 to 20 weeks after Stage 1 treatment initiation

• Number of Participants Who Successfully Consume a Single Dose of ≥600 mg of Milk Protein Without Dose-limiting Symptoms During the Double-blind Placebo-controlled Oral Food Challenge (DBPCFC) at the End of Stage 1

  During the DBPCFC at the end of Stage 1: 16 to 20 weeks after Stage 1 treatment initiation

• Number of Participants Who Successfully Consume a Single Dose of ≥600 mg of Egg Protein Without Dose-limiting Symptoms During the Double-blind Placebo-controlled Oral Food Challenge (DBPCFC) at the End of Stage 1

  During the DBPCFC at the end of Stage 1: 16 to 20 weeks after Stage 1 treatment initiation

Study Arms (7)

Stage 1:Omalizumab as Monotherapy

EXPERIMENTAL

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.

Drug: Omalizumab

Stage 1: Omalizumab OLE

EXPERIMENTAL

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.

Drug: Omalizumab

Stage 1: Placebo for Omalizumab as Monotherapy

PLACEBO COMPARATOR

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.

Drug: Placebo for Omalizumab

Stage 2: Omalizumab

EXPERIMENTAL

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.

Drug: Omalizumab

Stage 2: Omalizumab-Facilitated OIT

EXPERIMENTAL

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.

Drug: Omalizumab; Drug: Multi-Allergen Oral Immunotherapy

Stage 2: Omalizumab + Placebo OIT

EXPERIMENTAL

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.

Drug: Omalizumab; Drug: Placebo for Multi-Allergen Oral Immunotherapy

Stage 3: DBPCFC Based Treatment

OTHER

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.

Other: Double-Blind Placebo-Controlled Food Challenge Based Treatment

Interventions

Omalizumab 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.

Also known as: Xolair®

Stage 1: Omalizumab OLE; Stage 1:Omalizumab as Monotherapy; Stage 2: Omalizumab; Stage 2: Omalizumab + Placebo OIT; Stage 2: Omalizumab-Facilitated OIT

Placebo for Omalizumab 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.

Also known as: Placebo

Stage 1: Placebo for Omalizumab as Monotherapy

Multi-Allergen Oral Immunotherapy 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.

Also known as: Multi-Allergen OIT

Stage 2: Omalizumab-Facilitated OIT

Placebo for Multi-Allergen Oral Immunotherapy 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.

Also known as: Placebo for Multi-Allergen OIT

Stage 2: Omalizumab + Placebo OIT

Double-Blind Placebo-Controlled Food Challenge Based Treatment 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.

Also known as: DBPCFC Based Treatment

Stage 3: DBPCFC Based Treatment

Eligibility Criteria

• Age: 1 Year - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Individuals who meet all of the following criteria are eligible for enrollment as study participants:
• Participant and/or parent/legal guardian must be able to understand and provide informed consent and/or assent, as applicable;
• 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:
• Positive skin prick test (SPT) defined as ≥4 mm wheal greater than saline control) to peanut,
• Positive peanut immunoglobulin E (IgE), ≥6 kUA/L, at Screening or within three months of Screening, determined by ImmunoCap, and
• Positive double-blind placebo-controlled food challenge (DBPCFC), defined as experiencing dose-limiting symptoms at a single dose of ≤100 mg of peanut protein.
• 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:
• Positive SPT (≥4 mm wheal) to food,
• Positive food specific IgE (≥6 kUA/L) at Screening or within three months of Screening, determined by ImmunoCap, and
• Positive DBPCFC, defined as experiencing dose-limiting symptoms at a single dose of ≤300 mg of food protein.
• With body weight (as measured at Screening) and total serum IgE level (as measured within three months of Screening) suitable for omalizumab dosing;
• If female of child-bearing potential, must have a negative urine or serum pregnancy test;
• 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

You may not qualify if:

• Individuals who meet any of the following criteria are not eligible for enrollment as study participants:
• 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;
• Clinically significant laboratory abnormalities at Screening;
• Dose-limiting symptoms to the placebo portion of the Screening DBPCFC;
• 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).
• Poorly controlled atopic dermatitis (AD) at Screening, per the Principal Investigator's PI's) discretion;
• Poorly controlled or severe asthma/wheezing at Screening, defined by at least one of the following criteria:
• Global Initiative for Asthma (GINA) criteria regarding asthma control latest guidelines,
• 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,
• Prior intubation/mechanical ventilation for asthma/wheezing,
• One hospitalization or Emergency Department (ED) visit for asthma/wheezing within six months of Screening,

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Genentech, Inc.: collaborator
• Novartis Pharmaceuticals: collaborator
• Rho Federal Systems Division, Inc.: collaborator

Study Sites (10)

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

Little Rock, Arkansas, 72202, United States

Location

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

Stanford, California, 94305, United States

Location

National Jewish Health: Division of Pediatric Allergy and Clinical Immunology

Denver, Colorado, 80206, United States

Location

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

Atlanta, Georgia, 30307, United States

Location

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

Baltimore, Maryland, 21287, United States

Location

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

Boston, Massachusetts, 02114, United States

Location

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

New York, New York, 10029, United States

Location

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

Chapel Hill, North Carolina, 27599-7000, United States

Location

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

Philadelphia, Pennsylvania, 19104, United States

Location

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

Dallas, Texas, 75390, United States

Location

Related Publications (2)

• 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.

  PMID: 30586557 BACKGROUND

• 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.

  PMID: 38407394 RESULT

Related Links

• Division of Allergy, Immunology, and Transplantation
• National Institute of Allergy and Infectious Diseases

MeSH Terms

Conditions

Peanut Hypersensitivity

Interventions

Omalizumab

Condition Hierarchy (Ancestors)

Nut and Peanut Hypersensitivity; Food Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Anti-Idiotypic; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Serum Globulins; Globulins

Results Point of Contact

• Title: Director, Clinical Research Operations Program
• Organization: DAIT/NIAID

DAITClinicalTrialsGov@niaid.nih.gov

202-604-9855

Study Officials

• Robert A. Wood, MD

  Department of Pediatrics at the Johns Hopkins University School of Medicine

  STUDY CHAIR

• Sharon Chinthrajah, MD

  Department of Medicine, Stanford University School of Medicine

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 15, 2019
• First Posted: March 19, 2019
• Study Start: July 22, 2019
• Primary Completion: March 13, 2023
• Study Completion: July 1, 2025
• Last Updated: September 10, 2025
• Results First Posted: June 4, 2024

Record last verified: 2025-09

Locations

US (10)