Oral Immunotherapy for Food Allergies

(IMPROVES Trial)

Overseen By Liane Beaudette, RN

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre

Must not be taking: Immunosuppressors, Beta-blockers, NSAIDs, others

Disqualifiers: Uncontrolled respiratory disease, Cardiovascular disease, 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

360 Participants Needed

Trial Summary

What is the purpose of this trial?

Protocols for Oral Immunotherapy (OIT) for the main food allergens have been recently incorporated in clinical practice for food allergies and their clinical benefits have been acknowledged in European and Canadian official guidelines. There has been some reluctance in both clinicians and patients to implement these therapies, primarily because of the risk of allergic reactions during the desensitization process. This study will investigate if protocols using low doses of a food allergen or processed versions of the allergen can be both effective in conferring desensitization while inducing fewer allergic symptoms during the desensitization process.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as oral immunosuppressors, β-blockers, NSAIDs, aspirin, and ACE inhibitors. If you are on any of these, you would need to stop them to participate.

What data supports the effectiveness of this treatment for food allergies?

Research shows that oral immunotherapy (OIT) can help desensitize people with food allergies, allowing them to tolerate small amounts of the allergen. However, the benefits may decrease if the treatment is stopped, and there can be side effects. ^{1 2 3 4 5}

Is oral immunotherapy generally safe for humans?

Oral immunotherapy (OIT) for food allergies can cause adverse reactions, including serious ones like anaphylaxis (a severe allergic reaction). Safety concerns are a major barrier to its widespread use, and more consistent safety data is needed to better understand and manage these risks. ^{6 7 8 9 10}

How is the Modified Oral Immunotherapy treatment different from other treatments for food allergies?

Modified Oral Immunotherapy (OIT) is unique because it involves gradually introducing small amounts of the allergenic food to the patient to help their immune system tolerate it, unlike other treatments that mainly focus on avoiding the allergen. This approach aims to increase the threshold for allergic reactions, potentially reducing the risk of severe reactions from accidental exposure. ^{1 6 11 12 13}

Research Team

Moshe Ben-Shoshan, MD

Principal Investigator

MUHC-RI

Eligibility Criteria

This trial is for individuals with food allergies. Participants should be willing to undergo Oral Immunotherapy (OIT), which involves consuming small amounts of the allergen. The study aims to include those who are open to trying new desensitization protocols.

Inclusion Criteria

I have had a severe or moderate allergic reaction to a specific food within 2 hours of eating it.

I have a confirmed food allergy through skin or blood tests.

Exclusion Criteria

I am currently taking oral medication to suppress my immune system.

I take β-blockers, NSAIDs, aspirin, or ACE inhibitors daily for heart problems.

Non IgE mediated or non-immunological adverse reactions to milk or peanuts

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Desensitization

Participants undergo oral immunotherapy with low doses or processed versions of allergens to achieve desensitization

Varies by protocol

Maintenance

Participants maintain a stable dose of allergen to sustain desensitization

Up to 3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Modified Oral Immunotherapy

Trial Overview The study tests modified Oral Immunotherapy protocols using either low doses or processed versions of food allergens, aiming to reduce allergic reactions during treatment and still effectively desensitize patients against their food allergies.

Participant Groups

Group I: Standard Protocol - High Dose Arm Experimental Treatment 1 Intervention

Subjects will progress through desensitization to a high maintenance dose - 1200 mg of crushed peanut, 200 ml of milk or 1200 mg of egg powder.

Group II: Modified Protocol - Low Dose Arm Experimental Treatment 1 Intervention

Subjects will progress through desensitization to a low maintenance dose - 120 mg of crushed peanut, 50 ml of milk or 300 mg of egg powder.

Group III: Modified Protocol - Cooked/Transformed Allergen Arm Experimental Treatment 1 Intervention

Subjects will begin desensitization with cooked versions of the allergen (muffins in the case of egg and milk) or transformed versions (Bamba puffs for peanut). They will progress up to a full muffin or 4 Bamba puffs (for egg/milk and peanut respectively). Once subjects have reached these doses, they will transition to doses of pure allergen. They will then progress to the same top dose as subjects in the High Dose Arm.

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

Approved in United States as Palforzia for:

• Peanut allergy

Approved in European Union as Oral Immunotherapy for:

• Peanut allergy
• Egg allergy
• Milk allergy
• Other food allergies

Approved in Canada as Oral Immunotherapy for:

• Peanut allergy
• Other food allergies (research settings)

Who Is Running the Clinical Trial?

McGill University Health Centre/Research Institute of the McGill University Health Centre

Lead Sponsor

Trials

476

Recruited

170,000+

The Hospital for Sick Children

Collaborator

Trials

724

Recruited

6,969,000+

Findings from Research

Oral immunotherapy (OIT) is being developed as a patient-centered approach to treat IgE-mediated food allergies, with 38 recommendations created based on evidence and ethical considerations from a review of 162 articles and consultations with 85 individuals.

The guidelines emphasize shared responsibility between patients and healthcare providers, promoting patient empowerment and personalized treatment plans, while also addressing the need for equitable access and sustainability in food allergy care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CSACI guidelines for the ethical, evidence-based and patient-oriented clinical practice of oral immunotherapy in IgE-mediated food allergy. Bégin, P., Chan, ES., Kim, H., et al.[2022]

Oral immunotherapy (OIT) for cow's milk allergy (CMA) demonstrated a 100% clinical success rate in a study involving 59 children, leading to significant changes in immune responses, including increased levels of IgA and IgG4 antibodies after treatment.

The immune response to OIT was characterized by increased IL-10 cytokine levels and similar FoxP3 mRNA expression to those who developed natural tolerance, suggesting that OIT may effectively block IgE-mediated allergen presentation and promote tolerance mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunologic changes during desensitization with cow's milk: How it differs from natural tolerance or nonallergic state? Gunaydin, NC., Azarsiz, E., Susluer, SY., et al.[2022]

In a study of 31 children with egg allergies, oral immunotherapy (OIT) led to desensitization in 94% of participants, indicating it is an effective treatment for this condition.

After a 3-month egg avoidance period, only 31% of those desensitized maintained tolerance, suggesting that while OIT is effective for desensitization, long-term tolerance may not be guaranteed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral Immunotherapy for Egg Allergy: A Double-Blind Placebo-Controlled Study, with Postdesensitization Follow-Up. Caminiti, L., Pajno, GB., Crisafulli, G., et al.[2015]

Oral immunotherapy (OIT) has been shown to effectively desensitize patients with food allergies, leading to significant clinical improvements in allergy management, including sustained unresponsiveness in some cases.

The review highlights a need for a comprehensive understanding of the immune mechanisms involved in OIT, as current knowledge is limited and further research is necessary to fully elucidate how OIT modifies the immune response to allergens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune mechanisms of oral immunotherapy. Kulis, MD., Patil, SU., Wambre, E., et al.[2020]

The addition of omalizumab to milk oral immunotherapy (OIT) significantly reduced adverse reactions during treatment, with a marked decrease in the percentage of doses provoking symptoms (2.1% vs 16.1%) and dose-related reactions requiring treatment (0.0% vs 3.8%).

However, while omalizumab improved safety, it did not lead to better long-term efficacy outcomes, as the rates of desensitization and sustained unresponsiveness were similar between the omalizumab and placebo groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, double-blind, placebo-controlled study of omalizumab combined with oral immunotherapy for the treatment of cow's milk allergy. Wood, RA., Kim, JS., Lindblad, R., et al.[2022]

In a study of 68 children undergoing oral immunotherapy (OIT) for food allergies, about 90% were able to complete the treatment successfully, indicating that OIT can be effective for desensitization.

However, 9% of the children experienced severe adverse events (AEs) leading to discontinuation of the therapy, highlighting the importance of careful monitoring and the need for OIT to be conducted by trained professionals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of oral immunotherapy with cow's milk and hen egg: A 10-year experience in controlled trials. Pajno, GB., Caminiti, L., Chiera, F., et al.[2017]

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]

In a pilot study involving 6 subjects undergoing peanut oral immunotherapy (OIT), premedication with Ketotifen significantly reduced the rate of adverse reactions compared to a placebo, particularly during the initial escalation and build-up phases.

Ketotifen was well tolerated, with fatigue being the most common side effect, and it notably decreased gastrointestinal symptoms associated with peanut OIT, suggesting it may enhance the safety of this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of ketotifen premedication on adverse reactions during peanut oral immunotherapy. Jagdis, A., Berlin, N., Barron, C., et al.[2022]

In a review of real-world data, peanut oral immunotherapy (Ped-OIT) showed a low incidence of serious adverse reactions requiring epinephrine, with rates of 4.07% in preschool children and 3.1% in a broader age range, indicating it is relatively safe.

The safety profile of peanut Ped-OIT was found to be comparable to subcutaneous immunotherapy (SCIT), which had a higher incidence of systemic reactions at 7.4%, suggesting that Ped-OIT may be a viable alternative for treating peanut allergies in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing the risk of anaphylaxis requiring epinephrine in oral immunotherapy and subcutaneous immunotherapy: A review of recent Canadian real-world literature. Kovaltchouk, U., Jeimy, S., Soller, L., et al.[2023]

In a study involving 60 participants aged 2-25 with multi-food allergies, both low (300 mg) and high (1200 mg) doses of multi-food oral immunotherapy (mOIT) combined with omalizumab resulted in similar increases in IgG4/IgE ratios, indicating effective immune response.

The safety profile was comparable between the two dosing groups, with adverse events occurring in 19% of the low-dose group and 17% of the high-dose group, suggesting that lower doses may be a viable option for mOIT without compromising efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2, randomized multi oral immunotherapy with omalizumab 'real life' study. Sindher, SB., Kumar, D., Cao, S., et al.[2022]

Oral immunotherapy (OIT) is a promising method for treating food allergies by helping the immune system tolerate common allergens like milk, egg, and peanut, although it has only been able to desensitize patients to varying degrees.

Key challenges remain in optimizing OIT, including determining the best formulation, dosing, and safety protocols, which are crucial for its successful transition into clinical practice to enhance the quality of life for those with food allergies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral Immunotherapy for Treatment of Immunoglobulin E-Mediated Food Allergy: The Transition to Clinical Practice. Pajno, GB., Cox, L., Caminiti, L., et al.[2022]

In a study of 151 pediatric patients undergoing oral immunotherapy (OIT), 67.9% of those on single-food OIT and 86% of those on multifood OIT reached maintenance doses, indicating that both approaches are effective in desensitizing patients to food allergens.

The safety profile of OIT was favorable, with low rates of severe reactions: only 10.9% of initial dose escalations failed, and serious adverse events like epinephrine use and hospital admissions were very rare, suggesting that OIT can be safely implemented in an outpatient setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Multifood Oral Immunotherapy in Children Aged 1 to 18 Years at an Academic Pediatric Clinic. Nguyen, K., Lewis, MO., Hanna, E., et al.[2023]

In a study involving 20 adults with confirmed red meat allergies, all patients who underwent oral immunotherapy (OIT) became tolerant to red meat, demonstrating the long-term efficacy of this treatment for alpha-gal allergy.

Over a 5-year follow-up, the median levels of alpha-gal specific Immunoglobulin-E (sIgE) decreased in patients who consumed red meat, suggesting that sIgE could be a useful biomarker for monitoring the effectiveness of OIT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral immunotherapy in alpha-gal red meat allergy: Could specific IgE be a potential biomarker in monitoring management? Ünal, D., Eyice-Karabacak, D., Kutlu, A., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

CSACI guidelines for the ethical, evidence-based and patient-oriented clinical practice of oral immunotherapy in IgE-mediated food allergy. [2022]

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

Immunologic changes during desensitization with cow's milk: How it differs from natural tolerance or nonallergic state? [2022]

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

Oral Immunotherapy for Egg Allergy: A Double-Blind Placebo-Controlled Study, with Postdesensitization Follow-Up. [2015]

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

Immune mechanisms of oral immunotherapy. [2020]

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

A randomized, double-blind, placebo-controlled study of omalizumab combined with oral immunotherapy for the treatment of cow's milk allergy. [2022]

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

Safety profile of oral immunotherapy with cow's milk and hen egg: A 10-year experience in controlled trials. [2017]

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

Safety of Food Oral Immunotherapy: What We Know, and What We Need to Learn. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Effect of ketotifen premedication on adverse reactions during peanut oral immunotherapy. [2022]

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

Comparing the risk of anaphylaxis requiring epinephrine in oral immunotherapy and subcutaneous immunotherapy: A review of recent Canadian real-world literature. [2023]

10. Denmark pubmed.ncbi.nlm.nih.gov

Phase 2, randomized multi oral immunotherapy with omalizumab 'real life' study. [2022]

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

Oral Immunotherapy for Treatment of Immunoglobulin E-Mediated Food Allergy: The Transition to Clinical Practice. [2022]

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

Safety of Multifood Oral Immunotherapy in Children Aged 1 to 18 Years at an Academic Pediatric Clinic. [2023]

13. Denmark pubmed.ncbi.nlm.nih.gov

Oral immunotherapy in alpha-gal red meat allergy: Could specific IgE be a potential biomarker in monitoring management? [2023]