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

Trial Summary

What is the purpose of this trial?

Tree nut immunotherapy Route Assessment and DEvelopment (TRADE) is a randomized controlled trial that evaluates the efficacy and safety of sublingual immunotherapy and lower, more tolerable, doses of oral immunotherapy than currently in use.

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.

What data supports the effectiveness of the treatment Tree Nut Immunotherapy for tree nut allergies?

Research shows that oral immunotherapy (OIT) is effective for desensitizing people with food allergies like peanut, egg, and milk, suggesting it might also work for tree nut allergies. Additionally, sublingual immunotherapy (SLIT) has been effective for other allergies, like birch and grass pollen, indicating potential for tree nut allergy treatment. ^{1 2 3 4 5}

Is tree nut immunotherapy safe for humans?

Tree nut immunotherapy, including oral and sublingual methods, generally shows a good safety profile with most side effects being mild and local, such as irritation at the site of administration. Serious reactions are rare, and no fatalities have been reported in studies, but systemic reactions like urticaria (hives) and asthma can occur, especially with oral immunotherapy. ^{1 6 7 8 9}

How is Tree Nut Immunotherapy different from other treatments for tree nut allergies?

Tree Nut Immunotherapy is unique because it aims to desensitize individuals to tree nuts through oral or sublingual administration, potentially allowing them to tolerate nuts they are allergic to, unlike the current standard of strict avoidance. This approach is similar to immunotherapies used for other food allergies like peanuts, but it is still in the exploratory phase for tree nuts due to the complexity of multiple nut allergies and lack of standardized products. ^{1 4 10 11 12}

Research Team

Derek Chu, MD PhD FRCPC

Principal Investigator

Hamilton Health Sciences & McMaster University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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 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 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]

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]

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]

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]

References

1. England 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. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Clinical and immunological correlates of pre-co-seasonal sublingual immunotherapy with birch monomeric allergoid in patients with allergic rhinoconjunctivitis. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Utility of component analyses in subjects undergoing sublingual immunotherapy for peanut allergy. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Irradiated Tree Nut Flours for Use in Oral Immunotherapy. [2021]

5. Italy pubmed.ncbi.nlm.nih.gov

Sustained clinical efficacy of sublingual immunotherapy with a high-dose grass pollen extract. [2011]

6. Singapore pubmed.ncbi.nlm.nih.gov

[New administration routes for immunotherapy]. [2007]

7. Denmark pubmed.ncbi.nlm.nih.gov

Post-marketing surveillance study on the safety of sublingual immunotherapy in pediatric patients. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Local Side Effects of Sublingual and Oral Immunotherapy. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Safety of sublingual grass pollen immunotherapy after anaphylaxis. [2009]

10. United States pubmed.ncbi.nlm.nih.gov

New modalities of allergen immunotherapy. [2023]

11. England pubmed.ncbi.nlm.nih.gov

Tree nut allergies: Allergen homology, cross-reactivity, and implications for therapy. [2023]

12. England pubmed.ncbi.nlm.nih.gov

Differences and similarities between sublingual immunotherapy of allergy and oral tolerance. [2018]