Protocol for a double-blind, randomized controlled trial on the dose-related efficacy of omalizumab in multi-food oral immunotherapy

Abstract

Background: Previous proof-of-concept studies have shown that a short course of omalizumab can safely accelerate the oral immunotherapy schedule for multiple allergens simultaneously. Considering the high cost of medication, the dose-related efficacy of omalizumab at decreasing the duration of oral immunotherapy up-dosing phase must be objectively quantified before cost-benefit analyses can be performed. The primary objective of this trial will be to compare the efficacy of 2 omalizumab dosages to placebo at decreasing time-to-maintenance dose during a symptom-driven multi-food OIT protocol. Methods: A total of 90 participants aged 6 to 25 with multiple food allergies (3 or more) will be enrolled at four sites in Canada. Participants will be randomized to: (A) Omalizumab 8 mg/kg per month (n = 36); (B) Omalizumab 16 mg/kg per month (n = 36); or (C) Placebo (n = 18). Study drug will be administered at full dosage for 12 weeks, then progressively tapered at 50% dosage (8 mg/kg vs 4 mg/kg vs placebo) for 4 weeks and at 25% dosage (4 mg/kg vs 2 mg/kg vs placebo) for another 4 weeks. After a pre-treatment period of 8 weeks, participants will undergo an initial food escalation (IFE) to an OIT mix containing 3 allergens and start daily home dosing with biweekly increases until a target daily maintenance of 1500 mg protein is achieved. The amount escalated at each visit will vary based on treatment tolerance according to a standardized up-dosing algorithm. Participants will be followed for at least 12 months following the initial food escalation. The primary endpoint will be time from IFE to the target maintenance dose of 1500 mg protein. Time-toevent analytic methods, including the log-rank test, will be used to compare the 3 arms. Discussion: This trial uses a novel pragmatic approach to compare OIT with omalizumab to OIT without omalizumab in a blinded manner, which allows to single out the effect of this anti-IgE medication on treatment effectiveness speed without the recourse to predetermined schedules. The innovative patient-centered up-dosing algorithm allows to maximise treatment effectiveness speed without compromising patient safety, regardless of whether the patient is on omalizumab or not. This study will also provide novel prospective data to inform on the optimal and most costeffective dosage for this indication. Trial registration ClinicalTrials.gov, NCT04045301, Registered 5 August 2019, https ://clini caltr ials.gov/ct2/show/NCT04 04530 1

The use of biologics in food allergy

“…119 The Omalizumab to Accelerate a Symptom-driven Multi-food OIT (BOOM) study is evaluating how to maximize treatment speed within patient safety using a flexible pragmatic approach. 120 This is the first study to address the question of whether Omalizumab doses can be individualized for patients with food allergy, regardless of the standard dose used for respiratory allergy. lergy OIT it should be adjusted for body weight alone, independently of total IgE level.…”

“…Among these, the appropriateness of the dosage for this indication: in all probability, it is different from that of the dosage for asthma. 120 After initial encouraging findings, 109 real-life experiences indicate that food allergy symptoms may return upon discontinuation of Omalizumab. 108,125 In this sense, we cannot expect more from omalizumab than what we got from immunotherapy.…”

Economic considerations on the usage of biologics in the allergy clinic

“…A good example would be thrombolysis for stroke, in which the benefit of early intervention will we reaped for the rest of the patient's life in the form of While none of the biologics currently available in allergy have been shown to have disease-modifying effect, their use in combination with allergen immunotherapy to enable it in severe cases or to potentiate its effect is an important area of research, which could result in long-standing benefit after treatment discontinuation. 143 while taking into account the non-medical context (eg organizational, socio-political, environmental dimensions) ( Figure 7). [144][145][146][147][148][149][150][151] Also, because they are complex and based on various assumptions fully understood by only a few experts, cost-utility analyses generally lack transparency, 152 and therefore do not meet two of the key criteria of accountability for reasonableness (A4R), namely A) transparency about the grounds for decisions; and B) appeals to rationales that all can accept as relevant to meeting health needs fairly, which are meant to ensure that a decision process is legitimate and fair in a pluralist society.…”

Integrating oral immunotherapy into clinical practice

“…3 Oral immunotherapy (OIT) trials have primarily focused on peanut, cow's milk, and egg; however, wheat, tree nuts, and sesame OIT trials have been conducted, as well as multiallergen OIT. 2,[4][5][6][7][8][9][10][11] Only in 2020 was the first food allergy treatment, a peanut OIT drug called Palforzia (Aimmune Therapeutics, Brisbane, Calif), approved by the Food and Drug Administration (FDA). A peanut epicutaneous immunotherapy patch, Viaskin Peanut (DBV Technologies, Montrouge, France), was under FDA review.…”