Biologics for Food Allergies

No longer recruiting at 3 trial locations

Overseen By SNP Center Inquiry

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Stanford University

Must not be taking: Immunomodulators, Beta-blockers, ACE inhibitors, others

Disqualifiers: Cardiovascular disease, Severe anaphylaxis, Severe asthma, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 32 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of certain treatments for individuals with multiple food allergies, including peanut allergy. It aims to determine if treatments like omalizumab and dupilumab (a type of biologic therapy) can reduce allergic reactions. Participants will receive these treatments in various combinations or a placebo. The study seeks individuals with a history of peanut allergy and one or two other food allergies, such as milk or shellfish, confirmed by allergy tests. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that you stop using certain medications, such as immunomodulator therapy (except corticosteroids), beta-blockers, ACE inhibitors, ARBs, and calcium channel blockers. If you are on these medications, you may need to discuss alternatives with your doctor before participating.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Studies have shown that omalizumab is generally safe and well-tolerated. Most people experience mild side effects, such as reactions at the injection site, occurring in about 15.5% of cases. Serious reactions, like anaphylaxis, are rare and occur in about 0.2% of patients.

Research indicates that dupilumab is also well-tolerated. Some patients may experience mild side effects, but serious events like anaphylaxis are uncommon. One study found that most side effects of dupilumab were mild and not directly caused by the medication.

Both treatments are used for other conditions, which enhances understanding of their safety. Overall, these treatments have a good safety record based on previous research and use. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for food allergies because they offer new ways to potentially manage allergic reactions. Unlike traditional treatments, which often involve avoiding allergens or using antihistamines and epinephrine, Omalizumab and Dupilumab target specific immune pathways. Omalizumab works by binding to IgE antibodies, which play a crucial role in allergic responses, while Dupilumab inhibits IL-4 and IL-13 signaling, reducing inflammation. This targeted approach could provide better control over allergic reactions and improve quality of life for those with severe food allergies.

What evidence suggests that this trial's treatments could be effective for food allergies?

Research has shown that omalizumab, also known as Xolair, effectively treats food allergies. Studies have found it to be more effective than oral immunotherapy, which uses small doses of allergens to build tolerance, and it causes fewer side effects. People with multiple food allergies, including peanut allergies, have experienced better results with omalizumab. In this trial, participants in Cohort A will receive omalizumab for 8 weeks, followed by 24 weeks of placebo, while those in Cohort B will receive omalizumab for 8 weeks, followed by 24 weeks of dupilumab.

Dupilumab has also shown promise. Trials have demonstrated significant benefits by reducing allergy symptoms. It has been particularly effective in lowering total IgE levels, antibodies linked to allergic reactions. Participants in Cohort C will receive placebo for 8 weeks, followed by 24 weeks of dupilumab. Both treatments offer promising options for managing multiple food allergies. ^{3 5 6 7 8}

Who Is on the Research Team?

Rebecca S Chinthrajah, M.D.

Principal Investigator

Sean N Parker Center for Allergy and Asthma Center at Stanford

Are You a Good Fit for This Trial?

The COMBINE study is for people aged 4-55 with multiple food allergies, including peanut. Participants must have a confirmed allergy through specific tests and react to small amounts of allergens in a controlled challenge. They should not be severely asthmatic, pregnant, or on certain heart or immune-modifying medications.

Inclusion Criteria

You have a history of being allergic to peanuts and one or two other foods from a list that includes milk, almond, shellfish, fish, cashew, hazelnut, egg, walnut, sesame seeds, soy, and wheat. If you cannot eat both cooked and uncooked forms of milk and egg, it is considered an allergy.

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

Subject and/or parent guardian must be able to understand and provide informed consent

Exclusion Criteria

I am currently receiving immunotherapy for allergies or venom.

Pregnancy or lactation

Allergy to oat (placebo in DBPCFC)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive omalizumab or placebo for 8 weeks, followed by 24 weeks of treatment with either placebo or dupilumab, along with multifood allergen oral immunotherapy

32 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Dupilumab
• Omalizumab
• Placebo

Trial Overview This trial is testing the effectiveness of Omalizumab and Dupilumab—two biologic drugs—in improving outcomes for patients undergoing oral immunotherapy (OIT) for multiple food allergies compared to a placebo group.

How Is the Trial Designed?

Group I: Cohort C: Dupilumab Experimental Treatment 2 Interventions

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

Group II: Cohort B: Omalizumab/Dupilumab Experimental Treatment 2 Interventions

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

Group III: Cohort A: Omalizumab Experimental Treatment 2 Interventions

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

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Food Allergy Research & Education

Collaborator

Trials

6

Recruited

31,100+

Harvard School of Public Health (HSPH)

Collaborator

Trials

283

Recruited

17,030,000+

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborator

Trials

3,361

Recruited

5,516,000+

Published Research Related to This Trial

Peanut sublingual immunotherapy (SLIT) demonstrated a favorable long-term safety profile, with 98% of doses tolerated without severe reactions, and no use of epinephrine required during the study.

After 3 years of treatment, only 10.8% of participants achieved full desensitization to peanuts, indicating modest efficacy, while over 50% of subjects discontinued therapy before the study's conclusion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sublingual immunotherapy for peanut allergy: Long-term follow-up of a randomized multicenter trial. Burks, AW., Wood, RA., Jones, SM., et al.[2022]

Oral immunotherapy (OIT) for food allergies carries a risk of adverse reactions, including anaphylaxis, which is a significant barrier to its clinical use.

There is a need for an international consensus on safety reporting in OIT studies to better understand its safety profile and develop safer, individualized treatment pathways for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Food Oral Immunotherapy: What We Know, and What We Need to Learn. Vázquez-Cortés, S., Jaqueti, P., Arasi, S., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9142443/

Long-Term Efficacy and Safety of Dupilumab in Adolescents ... 16 weeks of treatment with dupilumab resulted in substantial clinical benefit compared with placebo, with an acceptable safety profile.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03682770

NCT03682770 | Study in Pediatric Subjects With Peanut ... Primary objective is to assess whether dupilumab as adjunct to AR101 compared to placebo improves desensitization at the completion of up-dosing.

3. jacionline.org jacionline.org/article/S0091-6749(22)01176-9/fulltext

Meta-analysis of the dupilumab atopic dermatitis database ... Dupilumab reduced the risk of new/worsening allergies by 34% (IRR 0.66; 95% confidence interval [CI], 0.52-0.84) and new allergies by 37% (IRR ...

4. annallergy.org annallergy.org/article/S1081-1206(25)00203-0/fulltext

Patient outcomes and safety of combination biologic ... Clinical outcomes were generally favorable, with improved disease control observed in 62.1% of cases. Combination biologic therapy with dupilumab is well- ...

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/all.16404

Efficacy and Safety of Dupilumab in Children With Peanut ... Dupilumab treatment resulted in around a 50% reduction in total IgE and ps-IgE. Abbreviations: DBPCFC, double-blind placebo-controlled food ...

6. link.springer.com link.springer.com/article/10.1007/s40257-025-00952-w

The Safety Data of Dupilumab for the Treatment ... The dupilumab label includes a warning for hypersensitivity reactions, including anaphylaxis, serum sickness or serum sickness-like reactions, ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02277769

NCT02277769 | Study of Dupilumab (REGN668 ... This is a randomized, double-blind, placebo-controlled, parallel-group study to confirm the efficacy and safety of Dupilumab monotherapy in adults with moderate ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2022/761055Orig1s040.pdf

761055Orig1s040 | FDA additional 52-week safety data from approximately 74 subjects who received dupilumab 300 ... have multiple food allergies by an allergist ...