Immunotherapy for Tree Nut Allergy

(TRADE Trial)

Overseen By Heather Le

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: Hamilton Health Sciences Corporation

Must not be taking: Biologics, Antihistamines, others

Disqualifiers: Anaphylaxis, Asthma, Pregnancy, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 1 year

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new methods for treating tree nut allergies using immunotherapy, which reduces the body's sensitivity to allergens. It compares two approaches: a low dose of oral immunotherapy (taken by mouth) and sublingual immunotherapy (placed under the tongue). The goal is to determine which method is more effective and safer for individuals with tree nut allergies. Those with a tree nut allergy who can safely consume small amounts of nuts without severe reactions might be suitable participants for this trial. As an unphased trial, this study provides a unique opportunity to explore innovative treatments for tree nut allergies.

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but you must stop taking antihistamines for 7 days before assessment visits.

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

Research has shown that tree nut oral immunotherapy (OIT) is generally safe, though some reactions can occur. In one study, 67% of patients experienced mild reactions, and about 32% had moderate reactions, with most being mild to moderate. The study reported no serious side effects.

For sublingual immunotherapy (SLIT), studies indicate it is well-tolerated, even by individuals with severe peanut allergies. SLIT involves placing a small amount of the allergen under the tongue and has been shown to be safe with daily treatment over a long period, such as 1 to 2 years.

Both methods are under study to help reduce allergy symptoms and improve tolerance to tree nuts. While mild reactions can occur, the studies mentioned reported no severe side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about tree nut immunotherapy because it offers a novel way to tackle tree nut allergies, which traditionally rely on avoidance and emergency treatments like epinephrine. This treatment uses both oral and sublingual immunotherapy, which are designed to gradually desensitize individuals to tree nuts by introducing them to small, controlled amounts of the allergen. Unlike current methods that don't modify the underlying allergy, these approaches aim to increase tolerance and reduce the severity of allergic reactions over time. With sublingual and low-dose oral immunotherapy, there's potential for a safer and more effective long-term solution for those with tree nut allergies.

What evidence suggests that this trial's treatments could be effective for tree nut allergy?

This trial will evaluate different approaches to tree nut immunotherapy. Research has shown that tree nut oral immunotherapy (OIT), which some participants in this trial will receive, is safe and effective. Studies have found that about 86% to 88% of people become desensitized, allowing them to eat tree nuts without a severe allergic reaction after treatment.

Sublingual immunotherapy (SLIT), which involves placing a small amount of the allergen under the tongue, is another treatment option in this trial. Research indicates that SLIT is also safe and effective for tree nut allergies. After 1 to 2 years of this treatment, many people can eat small amounts of tree nuts without issues. Both methods offer promising ways to manage and reduce tree nut allergies. ^{3 6 7 8 9}

Who Is on the Research Team?

Derek Chu, MD PhD FRCPC

Principal Investigator

Hamilton Health Sciences & McMaster University

Are You a Good Fit for This Trial?

The TRADE Trial is for individuals who are allergic to tree nuts and react to 444 mg of nut protein or less. Participants must consent to the trial, and if they're minors, they need parental consent as well.

Inclusion Criteria

Allergic to tree nut with baseline threshold of 444 mg protein or less and provides consent, and where applicable, assent.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive sublingual immunotherapy and/or low dose oral immunotherapy

1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Tree Nut Immunotherapy

Trial Overview This study tests two ways of treating tree nut allergies: sublingual immunotherapy (medicine placed under the tongue) and oral immunotherapy with lower doses than currently used. It's a randomized controlled trial, meaning participants are randomly assigned to different treatment groups.

How Is the Trial Designed?

Group I: Placebo low dose oral immunotherapy and Placebo sublingual immunotherapy Experimental Treatment 1 Intervention

Group II: Placebo low dose oral immunotherapy and Active sublingual immunotherapy Experimental Treatment 1 Intervention

Group III: Active low dose oral immunotherapy and Placebo sublingual immunotherapy Experimental Treatment 1 Intervention

Tree Nut Immunotherapy is already approved in United States, Canada, European Union for the following indications:

Approved in United States as Tree Nut Immunotherapy for:

• Tree nut allergy

Approved in Canada as Tree Nut Immunotherapy for:

• Tree nut allergy

Approved in European Union as Tree Nut Immunotherapy for:

• Tree nut allergy

Who Is Running the Clinical Trial?

Hamilton Health Sciences Corporation

Lead Sponsor

Trials

380

Recruited

345,000+

AAAAI Foundation

Collaborator

Trials

2

Recruited

2,100+

Published Research Related to This Trial

In a study of 73 patients with walnut allergy, 89% of those receiving walnut oral immunotherapy achieved desensitization to walnuts, compared to none in the control group, demonstrating its efficacy.

The therapy also resulted in cross-desensitization, with all co-allergic patients to pecan achieving desensitization, and significant rates of desensitization to hazelnut and cashew, indicating a broader impact on tree nut allergies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Walnut oral immunotherapy for desensitisation of walnut and additional tree nut allergies (Nut CRACKER): a single-centre, prospective cohort study. Elizur, A., Appel, MY., Nachshon, L., et al.[2020]

Gamma irradiation of walnut, cashew, hazelnut, and almond flours significantly reduces harmful microbial contamination without affecting total protein or allergen content, making these flours suitable for oral immunotherapy (OIT) trials.

The processed tree nut flours maintain stable microbial levels, protein, and allergen content over a 24-month period, ensuring they meet FDA standards for safety and efficacy in OIT drug products.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irradiated Tree Nut Flours for Use in Oral Immunotherapy. Penumarti, A., Szczepanski, N., Kesselring, J., et al.[2021]

Subcutaneous immunotherapy is a safe and effective treatment for allergic illnesses when administered correctly, with adverse reactions being mostly local and manageable.

Sublingual immunotherapy shows promise as a safer alternative, but its efficacy and safety, especially in children, remain insufficiently documented, leading to recommendations for its use only in controlled studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New administration routes for immunotherapy]. Martorell Aragonés, A.[2007]

Sublingual immunotherapy (SLIT) is generally safer than subcutaneous immunotherapy for treating respiratory allergies, with over 90% of adverse events being local and confined to the administration site, and no fatalities reported.

A specific grading system for local adverse events has been developed by the World Allergy Organization to improve the classification and reporting of SLIT safety, which is crucial for enhancing patient monitoring and regulatory compliance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Local Side Effects of Sublingual and Oral Immunotherapy. Passalacqua, G., Nowak-Węgrzyn, A., Canonica, GW.[2022]

Sublingual immunotherapy using modified allergen extracts significantly improved symptoms and reduced medication use in birch allergic patients during the pollen season, with a 30% and 40% improvement respectively compared to control subjects.

The treatment was associated with a decrease in allergen-specific T cell proliferation and an increase in the regulatory cytokine IL-10, indicating a positive immune response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical and immunological correlates of pre-co-seasonal sublingual immunotherapy with birch monomeric allergoid in patients with allergic rhinoconjunctivitis. Burastero, SE., Mistrello, G., Paolucci, C., et al.[2019]

Allergen immunotherapy is advancing with new methods and formulations that improve safety and effectiveness, including various delivery routes like oral and sublingual options, which are particularly beneficial for food allergies.

The combination of allergen immunotherapy with Anti-IgE therapy helps reduce side effects associated with traditional subcutaneous and oral treatments, enhancing patient tolerability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New modalities of allergen immunotherapy. Ramesh, M., Karagic, M.[2023]

In a study involving 46 grass pollen-allergic patients, the third year of sublingual immunotherapy (SLIT) showed further improvement in allergy symptoms and reduced medication use compared to the second year.

The treatment was found to be safe over three years, with no serious adverse events reported, indicating that SLIT can provide sustained and enhanced clinical benefits for patients with grass pollen allergies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sustained clinical efficacy of sublingual immunotherapy with a high-dose grass pollen extract. Kuna, P., Samolinski, B., Worm, M., et al.[2011]

Tree nut allergies affect about 1% of the U.S. population and are rarely outgrown, with strict avoidance of all tree nuts recommended due to high cross-reactivity among different types.

While there are promising immunotherapy approaches for other food allergies, such as milk and peanut allergies, research on effective treatments for tree nut allergies is limited, though evidence suggests that immunotherapy may be a viable option based on T-cell cross-reactivity findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tree nut allergies: Allergen homology, cross-reactivity, and implications for therapy. Smeekens, JM., Bagley, K., Kulis, M.[2023]

A study involving 268 children aged 2-15 years showed that sublingual immunotherapy for respiratory allergies is well tolerated, with only mild side effects reported in 3% of patients, indicating a favorable safety profile.

The treatment resulted in positive clinical outcomes, with 80% of patients rating their results as excellent or good, suggesting that sublingual immunotherapy is an effective option for managing allergies in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-marketing surveillance study on the safety of sublingual immunotherapy in pediatric patients. Di Rienzo, V., Pagani, A., Parmiani, S., et al.[2019]

Sublingual immunotherapy (SLIT) is an effective treatment for allergic rhinoconjunctivitis and shows promise for managing mild to moderate allergic asthma, providing a viable alternative to traditional subcutaneous immunotherapy (SCIT).

Oral immunotherapy (OIT) is still in the exploratory phase but has demonstrated encouraging results in desensitizing patients with food allergies, indicating potential for broader applications in allergy treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differences and similarities between sublingual immunotherapy of allergy and oral tolerance. Moingeon, P., Mascarell, L.[2018]

Sublingual immunotherapy is a safe alternative for patients who have experienced anaphylaxis from subcutaneous grass pollen immunotherapy, as demonstrated in two case reports.

Unlike subcutaneous immunotherapy, which carries a risk of severe anaphylactic reactions, sublingual immunotherapy has a safer side effect profile with no reported cases of anaphylaxis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of sublingual grass pollen immunotherapy after anaphylaxis. Nichani, JR., de Carpentier, J.[2009]

In a study of 33 peanut-allergic individuals undergoing 12 months of sublingual immunotherapy (SLIT), 30% achieved desensitization, passing a food challenge with 2500 mg of peanut protein without symptoms.

Lower baseline levels of specific IgE antibodies against peanut and its components, particularly Ara h 2 and Ara h 3, were linked to successful desensitization, suggesting that these IgE levels could help predict treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Utility of component analyses in subjects undergoing sublingual immunotherapy for peanut allergy. Burk, CM., Kulis, M., Leung, N., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11250215/

A practical focus on oral immunotherapy to tree nuts - PMC There is available evidence that TN oral immunotherapy (OIT) is reasonably safe and effective. There are numerous nonpharmaceutical food products to facilitate ...

2. aaaai.org aaaai.org/tools-for-the-public/conditions-library/allergies/the-current-state-of-oral-immunotherapy

The Current State of Oral Immunotherapy Peanut, egg and milk OIT have been shown to desensitize approximately 60 to 80% of patients studied. Desensitization rates for other foods have not been as ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2213219823001174

Real-World Safety Analysis of Preschool Tree Nut Oral ... We found real-world preschool TN-OIT is safe, with comparable outcomes to preschool P-OIT. Although symptoms were common during buildup, nearly all were mild.

4. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/pai.14132

Current options in the management of tree nut allergy: A ... Collectively, desensitization was achieved in 88% of treated nuts, 89% in omalizumab multi-OIT, and 86% in multi-OIT alone, and tolerogenic ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9932561/

Oral immunotherapy for food allergy OIT is effective in inducing short-term DS for CM, eggs, and peanut, and recent data suggest its efficacy for other foods and for young children ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39357559/

Safety and Feasibility of Peanut, Tree Nut, and Sesame Oral ... No increased adverse outcomes were observed on multifood OIT. Of the 59 initial oral food challenges, objective reactions occurred during 42 ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2213219824009516

Safety and Feasibility of Peanut, Tree Nut, and Sesame ... No increased adverse outcomes were observed on multifood OIT. Of the 59 initial oral food challenges, objective reactions occurred during 42 challenges, most ...

8. allergyandasthmacare.com allergyandasthmacare.com/tree-nut-oral-immunotherapy-deemed-safe-for-preschoolers-under-investigation/

Tree nut oral immunotherapy deemed safe for preschoolers ... Among patients treated for one tree nut allergy, 53 (67%) had grade 1 reactions and 25 (31.6%) had grade 2 reactions, and 53% of these grade 2 reactions were ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT01546753

Walnut Oral Immunotherapy for Tree Nut Allergy Secondary outcomes were evaluated including safety and immune mechanistic parameters. Official Title. Walnut Oral Immunotherapy for Tree Nut Allergy.