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

NCT03679676 | Completed Phase 2 DMC FDA Drug

• 2 other identifiers: IRB-479355U19AI104209-07
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 3

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.

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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.

  44 weeks

Secondary Outcomes (4)

• 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

  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

  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.

  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

  Baseline and week 32 and/or 44

Study Arms (3)

Cohort A: Omalizumab

OTHER

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

Drug: Omalizumab; Other: Placebo

Cohort B: Omalizumab/Dupilumab

OTHER

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

Drug: Omalizumab; Drug: Dupilumab

Cohort C: Dupilumab

OTHER

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

Drug: Dupilumab; Other: Placebo

Interventions

Omalizumab DRUG

Omalizumab is injected every 2 to 4 weeks

Also known as: Xolair

Cohort A: Omalizumab; Cohort B: Omalizumab/Dupilumab

Dupilumab DRUG

Dupilumab is injected every 2 weeks combination, or placebo.

Also known as: Dupixent

Cohort B: Omalizumab/Dupilumab; Cohort C: Dupilumab

Placebo OTHER

Placebo is injected every 2 to 4 weeks

Cohort A: Omalizumab; Cohort C: Dupilumab

Eligibility Criteria

• Age: 4 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Stanford University: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• Food Allergy Research & Education: collaborator
• Harvard School of Public Health (HSPH): collaborator

Study Sites (3)

University of California Los Angeles (UCLA)

Los Angeles, California, 90095, United States

Location

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

Palo Alto, California, 94304, United States

Location

University of California San Diego (UCSD)

San Diego, California, 92123, United States

Location

Related Publications (1)

• 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.

  PMID: 38814736 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Hypersensitivity; Food Hypersensitivity; Peanut Hypersensitivity

Interventions

Omalizumab; dupilumab

Condition Hierarchy (Ancestors)

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

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

Study Officials

• Rebecca S Chinthrajah, M.D.

  Sean N Parker Center for Allergy and Asthma Center at Stanford

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Director, Clinical Research Unit

Model Details: This is a prospective Phase 2, single-center, multi-allergen OIT in participants with proven allergies to 2 or 3 different foods in which one must be peanut. Our intent to treat population will be 110 participants, ages 4 to 55 years with a history of multiple food allergies of 2 or 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 DBPCFCs at or before the 300 mg (444 mg cumulative) dosing level of FA proteins.

Study Record Dates

• First Submitted: September 19, 2018
• First Posted: September 20, 2018
• Study Start: February 5, 2020
• Primary Completion: April 15, 2025
• Study Completion: May 2, 2025
• Last Updated: May 21, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)