Clinical Study Using Biologics to Improve Multi OIT Outcomes (COMBINE)

Phase 2 Randomized Controlled Trial Using Biologics to Improve Multi OIT Outcomes

Food allergy is a serious public health concern that causes potentially-life threatening reactions in affected patients. The prevalence of food allergy in the United States (U.S.) has increased substantially and now affects 15 million patients:4-8% of children (6 million children, 30% with multiple food allergies) and about 9% of adults. This is a prospective Phase 2, multi-center, multi-allergen OIT study in participants with proven allergies to 2 or 3 different foods in which one must be peanut. The intent-to-treat population in the clinical study will be 110 participants, ages 4 to 55 years with a history of multiple food allergies of 2 to 3 different foods including peanut. Allergy will be confirmed by food allergen (FA)-specific Immunoglobulin E (IgE) levels or positive Skin Prick Test (SPT). Enrolled participants must be positive during the Double-blind Placebo-controlled Food challenge (DBPCFC) at or before the 300 mg protein (444 mg cumulative) dosing level of FA proteins.

Study Overview

• Status: Completed
• Conditions: Hypersensitivity; Peanut Hypersensitivity; Peanut Allergy; Food Allergy; Hypersensitivity, Food
• Intervention / Treatment: Drug: Omalizumab; Other: Placebo for Dupilumab; Drug: Dupilumab; Other: Placebo for Omalizumab

Detailed Description

This is a prospective Phase 2, multi-center, multi-allergen OIT study in participants with proven allergies to 2 or 3 different foods in which one must be peanut. The total population will be 110 participants, ages 4 to 55 years that present with a history of multiple food allergies of 2 or 3 different foods including peanut, food-allergen (FA)-specific Immunoglobulin E (IgE) levels or positive Skin Prick Test (SPT).

Enrolled participants must react positively during DBPCFCs at or before the 300 mg (444 mg cumulative) dosing level of FA proteins of 2 or 3 allergens in which one must be a peanut.

There will be three study cohorts, all will be double-blinded:

Cohort A (50 participants) will be treated with omalizumab for 8 weeks followed by 24 weeks of treatment with placebo for dupilumab. Cohort B (50 participants) will be treated with omalizumab for 8 weeks, followed by 24 weeks of treatment with dupilumab. Cohort C (10 participants) will be treated with placebo for omalizumab for 8 weeks followed by 24 weeks treatment with dupilumab. All participants will receive multi-allergen OIT for peanut plus one or two additional protocol-specified foods from week 8 through week 32.

• Study Type: Interventional
• Enrollment (Actual): 130
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • University of California Los Angeles (UCLA)
    • Palo Alto, California, United States, 94304
      • Sean N. Parker Center for Allergy & Asthma Research at Stanford University
    • San Diego, California, United States, 92123
      • University of California San Diego (UCSD)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 51 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 4 through 55 years (inclusive).
• Clinical history of peanut allergy and 1 or 2 additional foods from the following foods: milk, almond, shellfish, fish, cashew, hazelnut, egg, walnut, sesame seeds, soy, and wheat. Allergy to milk and egg is defined as unable to tolerate both cooked and uncooked forms.
• Positive allergy test determined by:
• ImmunoCAP serum IgE level >4 kilo Units of allergen per Liter (kUA/L) for each allergen within the past 12 months OR
• Skin prick test (SPT) ≥6 mm wheal diameter to each allergen.
• A clinical reaction during a DBPCFC to small doses of food defined as a cumulative dose of =/<444 mg food protein.
• No clinical reaction observed during the placebo (oat) challenge.
• Subject and/or parent guardian must be able to understand and provide informed consent.
• Written informed consent from adult participants.
• Written informed consent from parent/guardian for minor participants.
• Written assent from minor participants as appropriate (e.g., at and above the age of 7 years).
• Use of effective birth control by female participants of childbearing potential.

Exclusion Criteria:

• History of cardiovascular disease, including uncontrolled or inadequately controlled hypertension.
• Individuals less than 15 kg in weight at start of the study
• History of severe anaphylaxis to participant-specific foods that will be used in this study, defined as neurological compromise or requiring intubation.
• History of chronic disease (other than asthma, atopic dermatitis or allergic rhinitis) that is, or is at significant risk of becoming, unstable or requiring a change in chronic therapeutic regimen.
• History of eosinophilic esophagitis (EoE), other eosinophilic gastrointestinal disease, chronic, recurrent, or severe gastroesophageal reflux disease (GERD), symptoms of dysphagia (e.g., difficulty swallowing, food "getting stuck"), or recurrent gastrointestinal symptoms of undiagnosed etiology.
• Severe asthma (NAEPP EPR-3 Medication Criteria Steps 5 or 6)
• Mild or moderate asthma (NAEPP EPR-3 Medication Criteria Steps 1-4), if uncontrolled or difficult to control.

• Uncontrolled asthma as evidenced by:

  • FEV1 < 80% of predicted, or ratio of Forced Expiratory Volume in 1 second (FEV1) to forced vital capacity (FEV1/ Forced Vital Capacity (FVC)) < 75% of predicted, with or without controller medications (only for age 6 or greater and able to do spirometry reliably. If unable to do spirometry, Peak Expiratory Flow (PEF) of >80% is acceptable) or;
  • One overnight admission to a hospital in the past year for asthma or;
  • Emergency room (ER) visit for asthma within six months prior to screening.
• Inability to tolerate biological (antibody) therapies.
• Use of immunomodulator therapy (not including corticosteroids).
• Use of beta-blockers (oral), angiotensin-converting enzyme (ACE) inhibitors, angiotensin-receptor blockers (ARB) or calcium channel blockers.
• Current participation or within the last 4 months in any other interventional study.
• Pregnancy or lactation.
• Allergy to oat (placebo in DBPCFC).
• Use of investigational drugs within 16 weeks of participation.
• In build up phase of immunotherapy for aeroallergens or venom.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Cohort B: Omalizumab/Dupilumab; Participants will be treated with omalizumab for 8 weeks, followed by 24 weeks of treatment with dupilumab.	Drug: Omalizumab; Omalizumab is injected every 2 or 4 weeks; Other Names: Xolair; Drug: Dupilumab; Dupilumab is injected every 2 or 4 weeks combination, or placebo.; Other Names: Dupixent
Other: Cohort A: Omalizumab; Participants will be treated with omalizumab for 8 weeks, followed by 24 weeks of treatment with placebo for dupilumab.	Drug: Omalizumab; Omalizumab is injected every 2 or 4 weeks; Other Names: Xolair; Other: Placebo for Dupilumab; Placebo for dupilumab is injected every 2 or 4 weeks
Other: Cohort C: Dupilumab; Participants will be treated with placebo for omalizumab for 8 weeks, followed by 24 weeks of treatment with dupilumab.	Drug: Dupilumab; Dupilumab is injected every 2 or 4 weeks combination, or placebo.; Other Names: Dupixent; Other: Placebo for Omalizumab; Placebo for omalizumab is injected every 2 or 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Success Rates of Passing a Peanut Double-Blind Placebo Controlled Food Challenge (DBPCFC)	Success is defined as passing a cumulative dose of >=1,043 mg at the Week 44 DBPCFC if the subject has no or mild objective reactions. The primary endpoints would be compared between cohort A and cohort B. Outcome measures (rates) are presented as the percent of participants who passed, with the additional detail of the counts of participants who pass, and the participants who were analyzed.	44 weeks
The Success Rates of Passing a DBPCFC to Peanut and at Least One Other FA	Success is defined as passing a cumulative dose of >=1,043 mg at the Week 44 DBPCFC if the subject has no or mild objective reactions. The primary endpoints would be compared between cohort A and cohort B. Outcome measures (rates) are presented as the percent of participants who passed, with the additional detail of the counts of participants who pass, and the participants who were analyzed.	44 weeks
The Success Rates of Passing a DBPCFC to Peanut and Two Other FAs	Success is defined as passing a cumulative dose of >=1,043 mg at the Week 44 DBPCFC if the subject has no or mild objective reactions. The primary endpoints would be compared between cohort A and cohort B. Outcome measures (rates) are presented as the percent of participants who passed, with the additional detail of the counts of participants who pass, and the participants who were analyzed.	44 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Participants Who Successfully Pass DBPCFCs to a Cumulative Dose of >=1,043 mg Protein to 1, 2, or 3 FAs When Applicable at Week 44	Outcome measures (rates) are presented as the percent of participants who passed, with the additional detail of the counts of participants who pass, and the participants who were analyzed.	44 weeks
Proportion of Participants Who Successfully Pass DBPCFCs to a Cumulative Dose of ≥2,043 mg to 1, 2, or 3 FAs When Applicable at Week 32	Outcome measures (rates) are presented as the percent of participants who passed, with the additional detail of the counts of participants who pass, and the participants who were analyzed.	32 weeks
Proportion of Participants Who Pass DBPCFCs for Each FA at a Cumulative Dose of ≥1,043 mg, ≥2,043 mg, or ≥4,043 mg at Week 32 and/or Week 44.	Outcome measures (rates) are presented as the percent of participants who passed, with the additional detail of the counts of participants who pass, and the participants who were analyzed.	week 32 and/or 44
Proportion of Participants Who Have a 10-fold Change in the Cumulative Tolerance Dose for Each FA at Weeks 32 and/or Week 44, Compared to Baseline	Outcome measures (rates) are presented as the percent of participants who had a 10-fold change, with the additional detail of the counts of participants who had that change, and the participants who were analyzed.	Baseline and week 32 and/or 44

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID); Harvard School of Public Health (HSPH); Food Allergy Research & Education
• Investigators: Study Director: Rebecca S Chinthrajah, M.D., Sean N Parker Center for Allergy and Asthma Center at Stanford

Publications and helpful links

General Publications

• Ghelli C, Costanzo G, Canonica GW, Heffler E, Paoletti G. New evidence in food allergies treatment. Curr Opin Allergy Clin Immunol. 2024 Aug 1;24(4):251-256. doi: 10.1097/ACI.0000000000000999. Epub 2024 May 30.
• Long AJ, Sindher S, Martinez K, Choi JH, Albarran M, Schuetz J, Parry A, Tang J, Garcia Llorett M, Zedeck SS, Grissinger A, Kiernan E, Leonard S, Raeber O, Feight C, Anderson B, Sharma R, Bogetic D, Chin AR, Woch M, Poyser J, Laurienzo Panza J, Togias A, Wheatley L, Boyd S, Galli SJ, Nadeau KC, Chinthrajah RS. A phase 2 randomized controlled trial using biologics to improve multi OIT outcomes (COMBINE): design, rationale, and methods. Front Allergy. 2025 Dec 18;6:1729111. doi: 10.3389/falgy.2025.1729111. eCollection 2025.

Helpful Links

• Sean N. Parker Center for Allergy and Asthma Research

Study record dates

Study Major Dates

• Study Start (Actual): February 5, 2020
• Primary Completion (Actual): April 15, 2025
• Study Completion (Actual): May 2, 2025

Study Registration Dates

• First Submitted: September 19, 2018
• First Submitted That Met QC Criteria: September 19, 2018
• First Posted (Actual): September 20, 2018

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 28, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Food Allergy; Hypersensitivity, Peanut; Food Hypersensitivity; Allergy, Food
• Additional Relevant MeSH Terms: Nut and Peanut Hypersensitivity; Immune System Diseases; Hypersensitivity, Immediate; Hypersensitivity; Food Hypersensitivity; Peanut Hypersensitivity; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Antibodies, Anti-Idiotypic; Omalizumab; dupilumab
• Other Study ID Numbers: IRB-47935; 5U19AI104209-07 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No