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

NCT ID: NCT03679676

Last Updated: 2025-05-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 108 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-02-05
• Study Completion Date: 2025-05-02

Brief Summary

Food allergy (FA) 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, single-center, multi-allergen OIT study in participants with proven allergies to 2 or 3 different foods in which one must be a peanut. The total of participants in the clinical study will be 110, 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 FA-specific IgE levels and 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 (444 mg cumulative) dosing level of FA proteins.

Detailed Description

This is a prospective Phase 2, single-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 IgE levels, and 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. 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 8 weeks followed by 24 weeks treatment with dupilumab. All cohorts will receive multifood allergen oral immunotherapy.

Conditions

Hypersensitivity; Food Allergy; Hypersensitivity, Food; Peanut Hypersensitivity; Peanut Allergy

Study Design

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

Study Groups

Cohort A: Omalizumab

Participants will be treated with omalizumab for 8 weeks, followed by 24 weeks of treatment with placebo

Group Type: OTHER

Omalizumab

Intervention Type: DRUG

Omalizumab is injected every 2 to 4 weeks

Placebo

Intervention Type: OTHER

Placebo is injected every 2 to 4 weeks

Cohort B: Omalizumab/Dupilumab

Participants will be treated with omalizumab for 8 weeks, followed by 24 weeks of treatment with dupilumab.

Group Type: OTHER

Omalizumab

Intervention Type: DRUG

Omalizumab is injected every 2 to 4 weeks

Dupilumab

Intervention Type: DRUG

Dupilumab is injected every 2 weeks

combination, or placebo.

Cohort C: Dupilumab

Participants will be treated with placebo for 8 weeks, followed by 24 weeks of treatment with dupilumab.

Group Type: OTHER

Dupilumab

Intervention Type: DRUG

Dupilumab is injected every 2 weeks

combination, or placebo.

Placebo

Intervention Type: OTHER

Placebo is injected every 2 to 4 weeks

Interventions

Omalizumab

Omalizumab is injected every 2 to 4 weeks

Intervention Type: DRUG

Dupilumab

Dupilumab is injected every 2 weeks

combination, or placebo.

Intervention Type: DRUG

Placebo

Placebo is injected every 2 to 4 weeks

Intervention Type: OTHER

Other Intervention Names

Xolair; Dupixent

Eligibility Criteria

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 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), another 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 FEV1 to forced vital capacity (FEV1/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, 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.

• Minimum Eligible Age: 4 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: collaborator

Food Allergy Research & Education

OTHER

Sponsor Role: collaborator

Harvard School of Public Health (HSPH)

OTHER

Sponsor Role: collaborator

Stanford University

OTHER

Sponsor Role: lead

Responsible Party

R. Sharon Chinthrajah

Medical Director, Clinical Research Unit

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Rebecca S Chinthrajah, M.D.

Role: STUDY_DIRECTOR

Sean N Parker Center for Allergy and Asthma Center at Stanford

Locations

University of California Los Angeles (UCLA)

Los Angeles, California, United States

Sean N. Parker Center for Allergy & Asthma Research at Stanford University

Palo Alto, California, United States

University of California San Diego (UCSD)

San Diego, California, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 38814736 (View on PubMed)

Provided Documents

Document Type: Informed Consent Form

View Document

Related Links

http://med.stanford.edu/allergyandasthma/clinical-trials.html

Related Info

Other Identifiers

5U19AI104209-07

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB-47935

Identifier Type: -

Identifier Source: org_study_id