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

Alexandra Langlois, Marie-Hélène Lavergne, Hélène Leroux, Kerstin Killer, Pauline Azzano, Louis Paradis, Kathryn Samaan, Jonathan Lacombe-Barrios, Benoît Mâsse, Anne Des Roches, Philippe Bégin, Alexandra Langlois, Marie-Hélène Lavergne, Hélène Leroux, Kerstin Killer, Pauline Azzano, Louis Paradis, Kathryn Samaan, Jonathan Lacombe-Barrios, Benoît Mâsse, Anne Des Roches, Philippe Bégin

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-to-event 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 cost-effective dosage for this indication.Trial registration ClinicalTrials.gov, NCT04045301, Registered 5 August 2019, https://ichgcp.net/clinical-trials-registry/NCT04045301.

Keywords: Anti-IgE; Desensitization; Efficacy; Food allergy; Omalizumab; Oral immunotherapy; Randomized controlled trial; Safety.

Conflict of interest statement

Competing interestThe authors declare no conflict of interest related to the study. KS reports personal fees from Novartis outside the submitted work. ADR reports grants from Merk and ALK outside the submitted work. PB reports personal fees from Novartis, Pfizer, Sanofi, ALK and Aralez, as well as grants from DBV technologies, Regeneron and Sanofi outside the submitted work.

© The Author(s) 2020.

Figures

Fig. 1
Fig. 1
Conceptual model of omalizumab-enabled immunotherapy. ED50: Eliciting does triggering 50% of degranulation; IgE: immunoglobulin E; OIT: oral immunotherapy
Fig. 2
Fig. 2
The clinical equipoise. OMA: omalizumab; OIT: oral immunotherapy
Fig. 3
Fig. 3
Overall study design. DBPCFC: double-blind placebo-controlled food challenge; IFE: initial food escalation; OMA: omalizumab
Fig. 4
Fig. 4
Anaphylaxis reporting plan. SUSAR: suspected unexpected serious adverse reaction; ICF: informed consent form; IP: investigational product; AESI: adverse event of special interest, DSMB: Data Safety Monitoring Board; AE: adverse event; HC: Health Canada; REB: Research Ethics Board

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